Journal of Pakistan Association of
Dermatologists
Volume 13, Number 3 July-September, 2003
Editor
Ijaz Hussain
Associate Editors
Farhana Muzaffar
Zahida Rani
Faria Asad
Editorial Board
Abdul Ghafoor Qamar
Abdul Aziz Memon
Ahsan Hameed
Akhtar Waheed Khan
Ali Khan Tareen
Anjum Kanjee
Arif Maan
Ashfaq Ahmed Khan
Atif Hasnain Kazmi
Arfan-ul-Bari
Anoop Kumar
Badr S. Dhanani
Farooq Soomro
Ghulam Mujtaba
Hasina Thawerani
Iqbal Chowdhry
Iqbal Tareen
Iqbal Akhtar Khan
Jameel A. Shaheen
Jawaid Anwar
Khadimullah Kakakhel
Khalid Hussain
Khalid Makhdoomi
Khalid Hashmi
Khawar Khurshid
Liaqat Ali Khan
Mansoor Dilnawaz
Muhammad Jahangir
Nasser Rashid Dar
Nizamul Hussain
Naeem Iqbal
Naseema Kapadia
Pervaiz Iqbal
Raza Jaffery
Raza Muhammad Khan
S. M. Azam Bokhari
S.M. Shamim
Sabrina Suhail Pal
Sajid Mushtaq
Sharaf Ali Shah
Shehab Afzal Beg
Shahbaz Aman
Simeen Ber Rahman
Satish S. Savant
Tahir Anees
Tahir Jamil Ahmad
Tahir Saeed Haroon
Tariq Rashid
Tariq Zaman
Yasmeena Khan
Zarnaz Wahid
Zohra Zaidi
Zubair Memon
Publication Manager
Mr. Omar Abdul Aziz
JPAD, the official journal of Pakistan Association of Dermatologists is published quarterly,
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Copyright
 2003 Any material published in JPAD is copyright of Pakistan Association of
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2
Journal of Pakistan Association of
Dermatologists
Volume 13, Number 3 July-September, 2003
Contents
Editorial
Vitiligo. From Babechi to lasers.
Zahida Rani
112
Original articles
Autologous skin punch grafting in localized, fixed vitiligo
Tahir Jamil Ahmad, Tariq Rashid, Zahida Rani, Tahir Saeed Haroon
114
An audit of dermatoses at Baqai Institute of Skin Diseases, Karachi
Ijaz Ahmed, Mujeeb Ansari, Kashef Malick
117
Successful treatment of tinea capitis due to Microsporum canis with griseofulvin
Shahbaz Aman, Ijaz Hussain, Tahir Saeed Haroon
123
Lichen planus and hepatitis C virus infection: An epidemiologic study
Tameez-ud-deen, Shahzana Naqqash, Abdul Quddus Butt
127
Review articles
Zinc: An overview and therapeutic uses in dermatology
Arfan-ul-Bari, Simeen ber Rahman
130
Cockayne syndrome. An update.
Farhana Muzaffar, Ijaz Hussain
135
Surgical Pearl
Modifications in punch grafting
Tahir Jamil Ahmad, Tariq Rashid, Zahida Rani
146
Case reports
Acrodermatitis enteropathica in three siblings.
Arfan-ul-Bari, Muhammad Abbas, Simeen ber Rahman
148
A family with xeroderma pigmentosum-Cockayne syndrome complex
Ijaz Aman, Shahbaz Aman, Tahir Masood Ahmad
153
Quiz
An erythematous plaque on the breast
Faria Asad, Sabrina Suhail Pal
157
News
159
Information for authors
Editorial
Vitiligo. From Babechi to lasers.
Zahida Rani
Department of Dermatology, King Edward Medical College/Mayo Hospital, Lahore
Vitiligo is an acquired depigmentary
disorder which affects 1-3% of world
population without any age, sex, or racial
predilection. The disease has a great
negative
psychological
impact,
particularly, in coloured skin. The history
of disease is as old as that of mankind.
Treatment of vitiligo still remains
challenging as it was in the past. Due to
genetic predisposition, immune-mediated
injury, or other unidentified toxins,
melanocytes in the affected epidermis
disappear whereas those in the hair
follicles are spared. The treatment of
vitiligo is based on the principle of
repopulating the vitiliginous patches with
active melanocytes.
Photochemotherapy, in its crude form, was
practiced for the treatment of vitiligo as
early as 1500 to 1000 B.C. in India.
Babechi (in Urdu) or Bavanchi/Bavachi
(in Hindi), Psoralea corylifolia, is an
indigenous plant of Indian subcontinent.1
Different parts of the plant especially
seeds are rich in different psoralens. The
seeds in powdered form (1-3g/day) or
essential oil (oral as well as topical) have
been the mainstay of treatment for
leukoderma in the Eastern (Unani/
Ayurvedic) systems for centuries. The
first modern use of light therapy in
combination with purified topical and/or
oral psoralens was by E1 Mofty in 1948.2
Later, in 1976, high intensity sources for
UVA radiation were developed for the
treatment of vitiligo. Even today when a
number of other drugs (topical/oral
steroids, levamisole, immunosuppressants)
are available, the photo(chemo)therapy
retains the pivotal role. The modern
phototherapy aims at stimulation of
adjacent
melanocytes.
Phototherapy
comprises of topical and systemic
photochemotherapy (PUVA) and narrowband UVB. In the conventional
photochemotherapy, 8-methoxypsoralen is
administered in a dose of 0.5mg/kg,
followed by UVA irradiation at intervals
of 2 to 3 times weekly. Treatment has to
be continued for months to more than a
year. Partial repigmentation is seen in 3040% of cases and complete repigmentation
in fewer than 20% of patients.3 Systemic
PUVA is associated with a number of
acute and chronic hazards like increased
risk of cutaneous malignancies. In topical
PUVA, used for localized disease, 0.05%0.1% 8-methoxypsoralen is applied,
followed by UVA radiation at intervals of
2-3 times weekly. Repigmentation is seen
in about half of cases. Few researchers
used other photosensitizers e.g. khellin
(Ammi visnaga), phenylalanine, and
melagenina with UVA or infrared light, as
well.
Narrowband UVB phototherapy with a
spectrum of 311nm to 312nm and a peak
emission of 311nm has recently been
shown
as
effective
as
PUVA
photochemotherapy.
Njoo
et
al.4
demonstrated 75% repigmentation in 535
patients and stabilization of the disease in
80% of patients with only minimal side
effects. However, UVB photherapy and
112
PUVA, both modalities require regular
phototherapy sessions several times a
week for up to a year.
Based on the efficacy and safety of
narrowband UVB therapy, Spencer et al.5
embarked on a study of targeted
phototherapy using a single-wavelength
308nm UVB laser to treat focal areas of
vitiligo. The 308nm excimer laser has the
advantage of having increased precision
and the ability to deliver higher energy to
the target tissue in less time. In a pilot
study, they treated 29 patches of vitiligo
from 18 patients, using this laser with
120nanoseconds and 20Hz pulse, a 10x10mm spot size and a power output of
60mW. Lesions were treated 3 times a
week for a maximum of 12 treatments.
Some degree of repigmentation was
noticed in 57% and 82% of treated patches
after 6 and 12 treatments, respectively.
The degree of repigmentation in 2-4 weeks
achieved with laser therapy was much
higher than that achieved with other
available modes of vitiligo therapy.
Further studies are required to determine
the exact role of 308nm laser in vitiligo
treatment. Similarly, a larger spot size will
be required to make feasible the treatment
of larger body areas.
In case of localized, stable/fixed vitiligo
various
surgical
techniques
like
autologous minigrafts, punch grafts,
suction blister grafts, autologous thin
thiersch grafts have been used. These
procedures are associated with variable
degree of scarring. The addition of PUVA
therapy can expedite the process of
repigmentation. Ahmad et al.6 (in this
issue of JPAD) punch grafted 207
vitiliginous patches over different body
sites in 40 patients and added topical
PUVA, once the grafts were taken. They
reported >75% repigmentation in >85% of
patches after 6-12 months follow up. The
focused (cutting) mode CO2 laser has also
been used for punch grafting. Melanocyte
transplants, using either autologous pure
melanocyte
culture
or
autologous
melanocyte and keratinocytes co-cultures
are another experimental approach to treat
larger areas. However, the complexities of
the technique and required equipment are
the limiting factors.
The story of treatment of vitiligo does not
end here. Another area recently under
experimentation is the use of various
inflammatory mediators7 which will
stimulate
melanocyte
migration
proliferation e.g. receptor tyrosine kinase
growth factor, tumour growth factor along
with stem cell factor, leukotrienes
especially LTC4, LTD4, and G-protein
coupled with endothelin-1 insulin-like
growth factor etc. These mediators are
required for melanocyte proliferation,
chemokinesis and haptaxis. If successful,
these therapies will not require
phototherapy.
References
1.
2.
3.
4.
5.
6.
Behl PN, Arora RB, Srivastava G,
Malhotra SC, eds. Herbs useful in
dermatological therapy, 1st edn. Delhi:
CBS Publishers; 1993.
El Mofty A. A preliminary clinical report
on the treatment of leukoderma with Ammi
majus linn. J Roy Egy Med Assoc 1948;
31: 651-5.
Ortonne J. Psoralen therapy in vitiligo.
Clin Dermatol 1989; 7: 120-35.
Njoo MD, Bos JD, Westerhof W.
Treatment of generalized vitiligo in
children with narrow-band (TL-01) UVB
radiation therapy. J Am Acad Dermatol
2000; 42: 245-53.
Spencer JM, Nossa R, Ajmeri J.
Treatment of vitiligo with the 308-nm
excimer laser: A pilot study. J Am Acad
Dermatolo 2002; 46: 727-31.
Ahmad TJ, Rashid T, Rani Z, Haroon TS.
Autologous skin punch grafting in
localized, fixed vitiligo. J Pak Assoc
Dermatol 2003; 13: 114-7.
113
7.
Halder RM, Young CM. New and
emerging therapies for vitiligo. Dermatol
Clin 2000; 18: 79-88.
114
Original article
Autologous skin punch grafting in localized,
fixed vitiligo.
Tahir Jamil Ahmad, *Tariq Rashid, Zahida Rani, Tahir Saeed Haroon
Department of Dermatology, King Edward Medical College/Mayo Hospital, Lahore
*Department of Dermatology, Allama Iqbal Medical College/Jinnah Hospital, Lahore
Abstract Background A number of medical modalities including photo(chemo)therapy, topical and
systemic steroids etc. are used in the treatment of vitiligo. Surgical treatment like punch
grafting is recommended for localized, fixed disease.
Objectives To assess the clinical efficacy and safety of autologous skin punch grafting in
patients with localized, fixed vitiligo.
Patients and methods 40 adult cases (26 females and 14 males) having 207 localized vitiligo
patches, unresponsive to medical measures for more than a year were included in the study.
After investigations, they were subjected to test grafting and later to complete grafting of
involved areas. Donor grafts were taken from normal areas.
Results More than 85% patches showed good to excellent response after three months of
grafting and PUVA therapy. No alarming side effects were recorded.
Conclusion Autologous skin punch grafting is a safe, effective and promising mode of
treatment in cases of localized fixed vitiligo.
Key words
Autologous, punch graft, vitiligo.
Introduction
Vitiligo is an acquired achromic condition
occurring in 1% to 2% of the general
population affecting all races.1,2 When
exposed areas are involved, it may have
devastating aesthetic impact especially in
dark skinned people.3 The medical
treatment includes topical and systemic
steroids,
topical
and/or
systemic
methoxalen and ultraviolet light in the A
range, narrow band 311nm UVB, or
natural sunlight.4-7 Repigmentation is best
seen on face and neck (60-70%) and trunk
and limbs (40-50%). Hands, feet and lips
show even poorer results and segmental
Address for Correspondence
Dr. Tahir Jamil Ahmad
186 J, D.H.A., Phase 1, Lahore.
Ph # 042-5726937
vitiligo may show no response to topical
steroids and other modalities.8-13
There have been many reports of complete
repigmentation of vitiligo after localized
autologous minigrafting.6,7,13,15,16,17 We
planned this clinical study to evaluate its
efficacy and safety in our patients.
Patients and methods
Forty consecutive adult patients of vitiligo
were enrolled from 1998 to 2002 at the
department of dermatology, Mayo
Hospital, Lahore. All had localized, nonprogressive disease at almost every part of
the body for the last two to 20 years. All
had already tried a number of modalities
with no or minimum success. They were
115
investigated for bleeding disorders and
chronic illnesses. Each patient was test
punch grafted on one of the areas and
outcome was recorded after regular follow
up. All patients exhibiting satisfactory
pigmentation were subjected to punch
grafting on all the remaining sites.
Disposable punches of 4 mm were used
for both donor and recipient areas. Donor
grafts were usually taken from inner side
of upper arm, back of the ears and inner
side of thighs. Areas operated were
covered with surgical dressings for 48-72
hours. Any graft loss was replaced and
dressings were removed after one week.
Patients were started on PUVASOL or
PUVA in the chamber. The resulting
pigmentation and side effects were
recorded during follow up for one year.
Final assessment was made according to
the five scale system from G0 to G4 as
mentioned in Table 2. All the patients
were photographed before, during and
after treatment.
Results
Two hundred and seven patches of vitiligo
were punch grafted in these forty patients
(distribution given in Table 1). One
hundred and seventy four patches showed
G3 pigmentation or above in the range of
excellent pigmentation. Figure 1 and 2
show almost 100% repigmentation. Rest
of the patches showed variable
pigmentation and three of them did not
pigment at all despite repeated grafting.
Table 2 gives break up description of the
patches and their pigmentary response
after following them up for 6 months to
one year.
Table 1 Vitiligo distribution (n =40)
Area
Male
(n=14)
Female
(n=26)
Face
Neck
Trunk
12
2
19
7
No. of
vitiliginous
patches
(n=207)
48
20
2
3
1
7
2
3
14
12
7
13
12
12
28
26
15
20
31
19
Front
Back
Arms
Hands
Legs
Feet
Table 2 Results at 6 months - 1 year follow up
Grade of
repigmentation
G4
G3
G2
G1
G0
Patches
Result
105
69
21
9
3
Excellent
Very good
Good
Satisfactory
Poor
G4 = > 75% repigmentation; G3 = 50-75%
repigmentation, G2 = 25-50% repigmentation;
G1 = up to 25% repigmentation; G0 = no
repigmentation
Figure 1 Autologus punch grafting on
forehead
Discussion
Studies show 90% to 100% pigmentation
after minigrafting.14,15,17 When we compare
Figure 2 Complete repigmentation after six
months
116
our results with these studies, almost
similar
response
was
obtained.
Cobblestone appearance of the recipient
areas is well known.14,15,17 We, too, had
this problem earlier on but later, the use of
thin donor grafts in recipient wells
minimized it. However, no major
complication was encountered throughout.
Pigmentary improvement accomplished
with minigrafting is not only due to
melanin spread from the graft’s edges, but
also to melanocyte recolonization of the
epidermis within the achromic skin.7,19
Some of our cases did not respond after
repeated grafting and PUVA exposure.
The reason was not known but similar
problem is well known.7, 15, 19
Conclusion
Our results, when compared with those
from abroad, are quite promising and we
conclude that autologous skin punch
grafting of fixed vitiligo is a safe and
effective method of treatment of resistant
cases in our patients.
References
1.
2.
3.
4.
5.
6.
Shah SA, Aftab S, Goplani S. Prevalence
of vitiligo in skin clinic. J Pak Assoc
Dermatol 1991; 1: 14-9.
Najoo MD, Westerhof W, Bos JD,
Bossuyt PMM. A systemic review of
autologous transplantation methods in
vitiligo. Arch Dermatol 1998; 134: 15439.
Papadopolus L, Bor R, Legg C, Howk
JLM. Impact of life events on the onset of
vitiligo in adults. Preliminary evidence for
psychological dimension in aetiology.
Clin Exp Dermatol 1998; 23: 243-8.
Halder RM, Young CM. New and
emerging therapies for vitiligo. Dermatol
Clin 2000; 18: 79-88.
Qureshi AA, Qureshi AS, Shah SA.
Vitiligo. J Pak Assoc Dermatol 1992; 2: 116.
Boersma BR, Westerhof W, Bos JD.
Repigmentation in vitiligo vulgaris by
autologous minigrafting - results in
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
nineteen patients. J Am Acad Dermatol
1995; 33: 990-5.
Grimes PE. Vitiligo: an overview of
therapeutic approaches. Dermatol Clin
1993; 11: 325-38.
Njoo MD, Spuls PI, Boss JD, Bossuyt
PMM. Non surgical repigmentation
therapies in vitiligo: meta-analysis of the
literature. Arch Dermatol 1998; 134:
1532-40.
Njoo MD, Bos JD, Westerhof W.
Treatment of generalized vitiligo in
children with narrow band (TL-01) UVB
radiation therapy. J Am Acad Dermatol
2000; 42: 245-53.
Parsricha JS, Khaitan BK. Oral minipulse
therapy with betamethasone in vitiligo
patients having extensive or fast spreading
disease. Int J Dermatol 1993; 32: 753-7.
Sahin S, Hindioglhu U, Karaduman A.
PUVA treatment
of
vitiligo.
A
retrospective study of Turkish patients. Int
J Dermatol 1999; 38: 542-5.
Camacho F, Mazuecos J. Treatment of
vitiligo
with
oral
and
topical
phenylalanine: six years of experience.
Arch Dermatol 1999; 135: 1514-21.
Njoo MD, Westernhof W, Bos JD,
Bossuyt PMM. The development of
guidelines for the treatment of vitiligo.
Arch Dermatol 1999; 135: 1514-21.
Savant SS. Autologous miniature punch
grafting in stable vitiligo. Ind J Dermatol
Venereol Leprol 1992; 58: 310-4.
Orentreich N, Selmanowitz VJ. Autograft
repigmentation of leukoderma. Arch
Dermatol 1972; 105: 734-6.
Falabella R. Repigmentation of segmental
vitiligo by autologous minigrafting. J Am
Acad Dermatol 1983; 9: 514-21.
Falabella R. Treatment of localized
vitiligo by autologous minigrafting. Arch
Dermatol 1988; 124: 1649-55.
Billingham RE, Silvers WK. Studies on
the migratory behavior of melanocytes in
guinea pig skin. Int J Exp Med 1970; 131:
101-117.
Drake LA, Dinehart SM, Farmer ER et al.
Guidelines of care for vitiligo. J Am Acad
Dermatol 1996; 35: 620-6.
117
Original article
An audit of dermatoses at Baqai Institute of
Skin Diseases, Karachi.
Ijaz Ahmed, Mujeeb Ansari, Kashef Malick
Baqai Institute of Skin Diseases, Baqai Medical University, Karachi
Abstract Background Epidemiology offers one of the most powerful direct methods of evaluating skin
diseases in human population. The study comprises an audit of the patients presenting in the
outpatient department of Baqai Institute of Skin Diseases (BISD), during the calendar year
2002.
Patients and methods A total of 13105 patients presented in the outpatient department during
the said period. Their clinical diagnosis and results of relevant investigations were recorded.
Results Patients belonged to all age groups and both sexes with 6684 (51%) females and
6421 (49%) males. The most common disease as a single entity was found to be scabies
(15.4%). However, as a group, eczema accounted for 25% of the patients, followed by fungal
infections (12.6%), acne (8.5%) and bacterial infections (6.4%). Other important diseases
were melasma (4%), androgenetic alopecia (3.2%), diffuse alopecia (2.7%), urticaria (2.4%),
psoriasis (2.1%), viral infections (1.7%), alopecia areata (1.5%), lichen planus (1.3%), and
vitiligo (1.1%). Other less frequently reported diseases included drug eruptions, pediculosis,
post inflammatory hypo- and hyperpigmentation, generalized pruritus, oral ulcers, miliaria,
xanthelasma, milia, striae, palmoplantar keratoderma, leishmaniasis, leprosy, keloid and
vasculitis. Some rare diseases were pityriasis rosea, angioedema, ichthyosis, canities,
scleroderma, systemic lupus erythematosus and pemphigus. There were occasional case
reports of porokeratosis of Mibelli, Bowen’s disease, rosacea, mastocytosis and histiocytosis.
Conclusion Pattern of dermatoses at ‘BISD’ is much the same as in other cities of Pakistan
with minor differences.
Key words Epidemiology, skin diseases, hospital-based prevalence, frequency, Karachi,
Pakistan.
Introduction
Epidemiology offers one of the most
powerful direct methods of evaluating skin
diseases in human population.1 For an
epidemiological study, a large sample of
population is required so that the nature
and size of the health problems can be
Address for Correspondence
Dr. Ijaz Ahmad
36/2, Khayaban-e-Shujaat, D-H-A, Phase 5,
Karachi.
Ph # 021-584842, 021-5848454
adequately gauged. This in turn helps to
establish their importance in a community.
Not much epidemiological work has been
done in this field in our country. Although,
a few studies have been carried out at
Karachi,2 Lahore,3 and Bahawalpur4 in the
past but still there is a wide gap regarding
the national data.
Here we present an audit of dermatoses at
‘Baqai Institute of Skin Diseases’ (BISD),
118
affiliated with Baqai Medical University,
Karachi. This institute covers not only the
whole of Nazimabad, a thickly populated
area, but also the rest of previously called
district central of Karachi. Moreover,
patients also present here from adjoining
areas like Gulshan-e-Iqbal, New Karachi,
Banaras Colony, Qasba Colony, Garden
and Lasbela. In addition, patients coming
from remote areas like Malir and Landhi
and virtually the rest of Karachi present
here.
This study was aimed to determine the
frequency of various skin diseases in
patients presenting at BISD and to
compare the results with previous data
from our country.2-6
Patients and methods
During the calendar year 2002, a proper
record of all the OPD patients was
maintained at BISD. After a clinical
diagnosis, investigations, if required, were
also carried out. These included blood for
hematological and biochemical profile,
urine examination and X-ray chest.
Specific investigations included smears,
swabs and scrapings for microscopy and
culture from the lesional skin, radiological
examination, serology, skin biopsy and
rarely immunofluorescence.
Results
A total of 13105 patients attended the
OPD, during the said period. Patients
belonged to both sexes with 6684 (51%)
females and 6421 (49%) males. Of the
total patients 1956 (15%) were below 12
years of age. The minimum age of
presentation was 7 days and maximum 96
years. Patients belonged to all ethnic
groups.
Table 1 enlists the hospital-based
prevalence
of
different
disease
entities/groups in the descending order of
frequency. Scabies as a single entity, with
a frequency of 15.4% remained the most
common skin disease. However, as a
group of skin disorders, eczema topped the
list with a combined frequency of 25%.
This group included hand eczema (7.5%),
seborrhoeic dermatitis (3.4%), lichen
simplex chronicus (3%), atopic dermatitis
(2.6%), pityriasis alba (2.3%), xerotic
eczema (2.3%), allergic contact dermatitis
(2%), photodermatitis (0.7%), pompholyx
(0.7%), napkin dermatitis (0.4%) and
asteototic eczema (0.1%)
Fungal infections, as a group had a
frequency of 12.6%. The break up in the
descending order included, pityriasis
versicolor (4.2%), tinea capitis (2.9%),
tinea corporis (1.5%), onychomycosis
(1.1%), chronic paronychia (0.7%), tinea
cruris (0.7%), oral candidiasis (0.6%),
tinea pedis (0.5%), tinea manuum (0.2%)
and vaginal candidiasis (0.1%).
Table 1 Hospital-based prevalence of different
dermatoses (n=13105)
Disease
Eczemas
Scabies
Fungal infections
Sebaceous gland diseases
Hair follicle diseases
Bacterial infections
Pigmentary disorders
Papulosquamous disorders
Vascular disorders
Viral infections
Papular urticaria
Intertrigo
Drug eruptions
Tumours/cysts
Pediculosis
Keratinization disorders
Pruritus
Oral ulcers
Nevoid disorders
Leishmaniasis
Connective tissue disorders
Mycobacterial infections
Bullous disorders
Psychocutaneous disorders
Number
3282
2038
1640
1316
1029
840
809
465
362
224
147
105
90
69
68
64
55
51
31
31
27
26
18
14
%
25.0
15.4
12.6
10.1
8.0
6.4
6.2
3.5
2.8
1.7
1.1
0.8
0.7
0.5
0.5
0.5
0.4
0.4
0.2
0.2
0.2
0.2
0.1
0.1
119
Miscellaneous disorders
313
2.4
Table 2 Miscellaneous disorders (n=13105)
Disease
Burns
Miliaria
Xanthelasma
Skin tags
Striae
Corns
Keloids
Ingrowing toenails
Postherpetic neuralgia
Pitted keratolysis
Total
Number
56
47
42
37
35
32
24
17
16
7
313
%
0.4
0.4
0.3
0.3
0.3
0.2
0.2
0.1
0.1
0.1
2.4
Frequency of sebaceous gland disorders
was 10.1% and comprised acne (8.5%),
dandruff (1.5%) and rosacea (0.1%). The
disorders of hair follicles accounted for
8% of all the patients. The combined
frequency of alopecia was 7.6% with a
breakup of androgenetic alopecia (3.2%),
telogen effluvium (2.7%), alopecia areata
(1.5%) and drug-induced alopecia (0.2%).
Hirsutism (0.16%) and canities (0.1%)
were the other hair follicle diseases seen.
Total frequency of bacterial infections was
6.4%. This group included folliculitis
(1.8%), impetigo (1.5%), furunculosis
(1.3%), ecthyma (1.1%), cellulitis (0.4%)
and periporitis (0.3%).
Frequency of disorders of pigmentation
(6.2%) included melasma (4%), vitiligo
(1.2%),
postinflammatory
hypopigmentation
(0.5%)
and
postinflammatory
hyperpigmentation
(0.5%). Papulosquamous disorders i.e.
psoriasis vulgaris (2.1%), lichen planus
(1.3%) and pityriasis rosea (0.1%) had a
combined frequency of 3.5%.
The group of vascular disorders accounted
for 2.8% of the patients and included
urticaria (2.4%), vasculitis (0.2%),
angioedema (0.1%) and Schamberg’s
disease (0.1%).
Viral infections (1.7%) included common
warts (0.4%), molluscum contagiosum
(0.4%), chicken pox (0.3%), verruca plana
(0.2%), herpes simplex (0.2%), genital
warts (0.1%) and herpes zoster (0.1%).
Papular urticaria and intertrigo were
reported in 1.1% and 0.8% patients,
respectively. The combined frequency of
drug
eruptions
(0.7%)
included
generalized drug eruption (0.6%) and
fixed drug eruption (0.1%). The group of
tumors and cysts included milia (0.2%),
syringomas (0.1%), pyogenic granulomas
(0.05%),
mastocytosis
(0.05%),
histiocytosis (0.05%) and Bowen’s disease
(0.05%). The frequency of pedicu1osis
capitis was (0.5%).
Frequency of disorders of keratinization
(0.5%) had the following break up:
palmoplantar
keratoderma
(0.2%),
ichthyosis (0.2%), lichen spinolosus
(0.04%), porokeratosis of Mibelli (0.03%)
and lichen striatus (0.03%). Generalized
pruritus (0.4%), oral ulcers (0.4%) and
cutaneous leishmaniasis (0.2%) were a
few other disorders seen.
Nevoid disorders (0.3%) included
1entigines (0.1%), hemangiomas (0.1%)
and
adenoma
sebaceum
(0.1%).
Connective tissue diseases (0.2%)
included scleroderma (0.1%) and lupus
erythematosus (0.1%).
Leprosy (0.2%) and tuberculosis cutis
(0.1%) were seen rarely.
Amongst the bullous disorders, pemphigus
vulgaris and bullous pemphigoid had a
frequency
of
0.05%
each.
Psychocutaneous disorders (0.1%) were
again rarely reported.
120
Some other diseases included in the
miscellaneous group are shown in
Table 2.
Discussion
Karachi is the largest city of Pakistan, a
thickly populated metropolis with a
population around 15 millions. It is a city
with executives working in offices as well
as labourers working for long hours in the
sunlight. The weather here is hot and
humid throughout the year with winter
season lasting a few days. Such weather
could be responsible for different
cutaneous infections. The population of
Karachi is a mixed one, with people
belonging to different ethnic groups and
coming from different areas of our
country. This factor accounts for diseases
like leishmaniasis being transported from
endemic areas. Lack of health education,
poverty, illiteracy, poor hygiene and
communal living are other contributory
factors.
Table 3 compares the hospital-based
prevalence of different dermatoses in
previous studies with that in the present
one. Scabies as a single entity, with a
frequency of 15.4% remained the most
common skin disease in Karachi, as in
other parts of Pakistan. In all the past
studies, scabies topped the list.2-4
As a group of skin disorders, eczema
topped the list with a combined frequency
of 25%. Hand eczema (7.5%) was the
most common, a diagnosis not mentioned
as a distinct entity in any of the past
studies.2-4 Seborrhoeic dermatitis (3.4%)
had a frequency significantly lower than
that reported in previous studies.2-4 Lichen
simplex chronicus was the common type
of eczema in our series with a frequency
of 3%, not reported from Karachi in the
past.2 However, this frequency is almost 3
times higher than that reported from
Bahawalpur4 (1%) and Lahore3 (1%). The
frequency of atopic dermatitis (2.6%) was
almost double than that reported from
Bahawalpur4 (1.2%). Muzzafar et al.5
reported a frequency of 13.3% at Children
Hospital, Lahore. The frequency of
pityriasis alba (2.4%) was 2.5 times higher
than that reported from Bahawalpur4 and
Karachi.2 A higher percentage of children
in our series may account for this figure.
Xerotic eczema (2.3%) had no comparable
figures in the past studies.2-4 Allergic
contact dermatitis seen in 2% of patients,
had a frequency significantly lower than in
Bahawalpur4 (4.8%). Nadeem et aI.6
reported contact dermatitis in 10% of
patients, out of which 30-50% were
allergy-related. No comparable figures
were available for photodermatitis,
pompholyx, napkin dermatitis and
asteototic eczema.2-4
The prevalence of fungal infections, as a
group, was 12.5%, in agreement to that
seen in Karachi2 (12.6%) and Bahawlpur4
(10.7%). The hot and humid climate of
Karachi may be responsible for this high
prevalence.
Acne vulgaris had a frequency of 8.5% in
our series, much higher than that reported
previously from Karachi2 (2.8%) and
Lahore3 (1.6%) but similar to that reported
from Bahawalpur4 (7%). Does it show a
real increase in the occurrence of acne or
patients have become more cosmeticconscious, needs to be determined.
The disorders of hair accounted for 8% of
all patients. Alopecia was seen in 7.6%
patients with androgenetic alopecia
(3.2%), telogen effluvium (2.7%), and
alopecia areata (1.5%) as common causes.
Hirsutism (0.2%) and canities (0.1%) were
121
Table 3 Comparison of prevalence rate of different disease in the present study with previous studies
Disease
Scabies
Eczema
Atopic
Lichen simplex chronicus
Contact dermatitis
Fungal infections
Bacterial infections
Tuberculosis cutis
Viral infections
Acne
Disorders of hyperpigmentation
Vitiligo
Urticaria
Psoriasis
Pityriasis rosea
Fixed drug eruption
Ichthyosis
Lupus erythematosus
Karachi
1985 [2]
22.4%
Lahore 1961
[3]
9.6%
Bahawalpur
2000 [4]
14.6%
Present
2003
15.4%
12.6%
12.8%
0.7%
2.5%
2.8%
1.3%
3.1%
0.7%
0.2%
0.8%
0.7%
0.4%
1%
4.8%
17.5%
0.6%
0.7%
1.6%
1.2%
1.5%
2%
2%
-
1.2%
1%
4.8%
10.7%
5.9%
0.4%
3.7%
7%
3.3%
1.6%
4.9%
1.8%
0.2%
0.6%
0.5%
0.6%
2.6%
3%
2%
12.5%
6.4%
0.1%
1.7%
8.5%
6.2%
1.2%
2.4%
2.1%
0.1%
0.1%
0.4%
0.1%
rare. No comparable data were available
for these conditions.
The overall prevalence of bacterial
infections (6.4%) was significantly lower
than that previously reported from
Karachi2 (12.8%) and Lahore3 (17.5%) but
comparable to figure from Bahawalpur.4
The most common bacterial infection in
this series was folliculitis as reported by
Kanjee et al.7 in 2001 at Jinnah
Postgraduate Medical Centre, Karachi.
Folliculitis remains the most common
bacterial infection in Karachi. Hot
weather, poor hygiene, communal living
leading to frequent physical contact and
lack of proper and timely advice are a few
factors accounting for a high frequency of
bacterial infections.
Among the disorders of pigmentation,
melasma was the commonest, as reported
all over the country.2-4 We found a
frequency of 4%. It may be due to a higher
percentage of female patients in our series.
Vitiligo (1.2%) had a frequency similar to
that from Bahawalpur4 (1.6%) and Lahore3
(1.5%).
The prevalence of psoriasis vulgaris
(2.1%) was higher than that from Karachi2
(0.7%), but similar to that from Lahore3
(2%) and Bahawalpur4 (1.8%). Pityriasis
rosea had a comparable figure to that from
Karachi2 (0.2%) and Bahawalpur4 (0.2%).
In the group of vascular disorders urticaria
(2.4%) was the major disorder. Its
prevalence was significantly less than that
from Bahawalpur4 (4.9%) but almost
similar to that from Karachi2 (3.1%) and
Lahore3 (2%).
The combined frequency of viral
infections (1.7%) was less than that seen
in Bahawalpur4 (3.7%) and Karachi2
(2.5%) but higher than that from Lahore3
(0.7%).
Cutaneous leishmaniasis is an endemic
disease in various areas of Pakistan and of
late there been an increase in case reports
from different areas of Sindh.8-10 In the
current series, the frequency of cutaneous
leishmaniasis was 0.2%. All these patients
presented from Gaddap town.
Amongst mycobacterial infections, leprosy
was seen in 0.2% patients. Karachi is one
of the endemic area for leprosy and
according to an estimate Karachi is
believed to harbor around 20,000 infected
122
persons who will develop leprosy in the
next 10-20 years.11 Tuberculosis cutis,
(0.1%) was less frequent than that reported
by all the compared studies; Karachi2
(0.7%), Lahore3 (0.6%), and Bahawalpur4
(0.4%). All the cases in our series suffered
from lupus vulgaris, although Khan et al.12
reported scrofuloderma to be the most
common type of tuberculosis cutis in
Pakistan.
For drug eruptions, tumours, the disorders
of keratinization, bullous disorders,
connective diseases, and psychocutaneous
diseases, the prevalence rate was less than
1%, similar to that from other cities.2-4
Conclusion
It can be concluded from the above study
that the pattern of skin diseases is same in
various cities of Pakistan with minor
differences in frequency. Scabies being the
most common disease necessitates a need
for better health education, improved
hygiene and better living standards.
7.
Kanjee A, Yasmeena N, Siddiqi K. Effect
and tolerability of cephradine in bacterial
skin infections. J Pak Assoc of Dermatol
2002; 12: 18-20.
8. Mujtaba G, Khalid M. Cutaneous
leishmaniasis in Multan, Pakistan. Int J
Dermatol 1998; 37: 843-6.
9. Raja KM, Khan AA, Hameed A. Unusual
clinical
variants
of
cutaneous
leishmaniasis in Pakistan. Br J Dermatol
1998; 139: 111-3.
10. Khan I, Khan MA. Managing cutaneous
leishmaniasis from Peru to Pakistan. J Pak
Assoc Dermatol 2000; 10: 5-15.
11. Jabeen S, Shaikh A, Sheikh AR.
Psychological aspects of female leprosy
patients. J Pak Assoc Dermatol 2000;
10:16-20.
12. Khan Y, lqbal P, Kumar A. Cutaneous
tuberculosis: A study of 10 cases. J Pak
Assoc Dermatol 200l; 11: 7-10.
References
1.
2.
3.
4.
5.
6.
Williams HC. Epidemiology of skin
diseases. In: Champion RH, Burton JL,
Burns DA, Breathnach SM, eds. Textbook
of dermatology, 6th edn. Oxford:
Blackwell Science; 1998. p.139-57.
Haroon TS. Pattern of skin diseases in
Karachi. J Pak Med Assoc 1985; 35: 73-8.
Shabbir G. Dermatoses prevalent in
Lahore. The Medicus 1961; 22: 33-42.
Qamar AG, Malik RA. Skin diseases in
Bahawalpur. J Pak Assoc Dermatol 2000;
10: 3-8.
Muzzafar F, Hussain I, Rashid T. An audit
of childhood eczema. J Pak Assoc
Dermatol 2000; 10: 9-14.
Nadeem M, Akber T, Haroon TS. Patch
testing with European standard series, our
experience at Mayo hospital Lahore. J Pak
Assoc of Dermatol 2001; 11: 7-12.
123
Original article
Successful treatment of tinea capitis with
griseofulvin caused by Microsporum canis.
Shahbaz Aman, Ijaz Hussain, Tahir Saeed Haroon
Department of Dermatology, King Edward Medical College/Mayo Hospital, Lahore
Abstract
Background Griseofulvin is an antimycotic which has been used successfully as a treatment
of tinea capitis caused by dermatophytes.
Objective Our aim was to assess the efficacy of griseofulvin therapy in tinea capitis caused by
zoophilic species, Microsporum canis.
Patients and methods Nine mycologically confirmed cases of inflammatory and noninflammatory tinea capitis were enrolled in the study. Griseofulvin therapy was started
10mg/kg once daily at night with milk for 8 weeks and the patients were followed up to 8
weeks after the completion of therapy.
Results Of 9 patients, 4 were males while 5 were female children. The age ranged from 6 to
12 years. The agminate folliculitis type was noted in five patients and grey patch variety was
seen in four patients. Microsporum canis was the pathogen isolated in all cases. The patients
were prescribed griseofulvin. Clinical cure was seen in 89% cases while mycological cure
was seen in 100% patients at 16 weeks final evaluation (8 weeks after the completion of
therapy). The adverse events were few, mild and reversible in nature.
Conclusion Griseofulvin was found to be effective, well-tolerated and safe therapy for tinea
capitis caused by Microsporum canis.
Key words
Tinea capitis, griseofulvin, Microsporum canis.
Introduction
Tinea capitis is a fungal infection of scalp,
skin and hair characterized by erythema,
scaling, pruritus and alopecia.1 Like other
dermatophytoses, tinea capitis is also
common in this part of the world. Clinical
patterns
of
the
disease
include
noninflammatory (grey patch and black
dot) or inflammatory (kerion celsi,
agminate folliculitis and favus) types2
caused by dermatophytes of both genera
Trichophyton
and
Microsporum.3
Although
grey
patch
variety is
encountered most frequently but agminate
Address for Correspondence
Dr. Shahbaz Aman
2-C Hearn Road, Islampura
Lahore.
Ph# 042-7226054
folliculitis is not uncommon in our
society.1,2,3 Tinea capitis caused by M.
Canis is a difficult therapeutic problem
which requires an adequate antimycotic
therapy.4
Griseofulvin is a metabolic product of
Penicillium griseofulvum, firstly described
in 1939.5 It acts on microtubules and
inhibits fungal mitosis.5 Absorption occurs
primarily from the duodenum and jejunum
while some quantity also absorbed from
ileum, stomach and rectum.5 The peak
plasma level occurs between 2 and 9 hours
after administration and remains high for
10 to 20 hours. It is effective for the
infections of skin, hair and nails caused by
dermatophytes but not against Candida
124
spp.5
We report nine cases of tinea capitis due to
M. canis and their successful treatment
with griseofulvin therapy.
Patients and Methods
This was an open, clinical, pilot study.
Nine children presented with clinically
suspected tinea capitis at the mycology
clinic of the Department of Dermatology,
King Edward Medical College/Mayo
Hospital, Lahore were included in the
study after taking informed consent. A
detailed history and meticulous clinical
examination was recorded. The lesions
were examined clinically and under
Wood’s light for any fluorescence. To
confirm the diagnosis, specimens from
affected scalp area along with hair were
taken. The specimens were examined
under light microscope after treating with
25% potassium hydroxide and fluorescent
microscopy was also done after using
calcofluor white stain. For fungus culture,
the specimens were inoculated on
Sabouraud’s dextrose agar together with
chloramphenicol and with or without
cycloheximide. The cultures were
incubated at 25-300C for 4 to 6 weeks and
were examined twice weekly to confirm
any negative growth. The positive cultures
were identified by gross colonial
morphology
and
microscopic
characteristics after making teased mounts
of a mature colony and stained with
lactophenol cotton blue.
The criteria for inclusion in the study were
clinical and mycological evidence of
dermatophytosis of the scalp. Those
patients who had topical antifungal
therapy within 2 weeks or oral antifungal
agents within 4 weeks of entering the
study were excluded from the study.
Patients who had any concomitant topical
or systemic treatment were also excluded
from the study. Treatment was
administered 10mg/kg once daily at night
with milk. The therapeutic efficacy of the
drug was determined by evaluation at
every 2 weeks, end of treatment and at
follow-up period by observing the clinical
signs, symptoms and mycological
examination. The clinical parameters were
assessed according to a four-point scale
ranging
from
(0=absent,
1=mild,
2=moderate, and 3=severe) for erythema,
scaling (desqumation), edema, pustules,
pruritus and hair loss. Hematological
investigations performed for each patient
before, during and if needed after the
treatment were: hemoglobin, hematocrit,
white cell count, bilirubin, serum glutamic
oxaloacetic transaminase (SGOT), serum
glutamate pyruvic transaminase (SGPT),
lactate dehydrogenase (LDH), alkaline
phosphatase, gamma glutamyl transferase,
potassium,
creatinine,
uric
acid,
cholesterol and triglycerides.
Results
Of 9 patients, 4 were males while 5 were
female children (Table 1). The age ranged
from 6 to 12 years (mean age, 7.7+2.02
years). The agminate folliculitis variety
was seen in 5 patients while grey patch
variety was noted in four patients (Figure
1). Physical examination revealed scaling,
erythema, pustules, pruritus and alopecia.
There was a history of exposure to pet
animals (dogs=3, cats=2) in our patients
but there was no history of trauma, drug
intake, application of medicament or other
skin diseases like psoriasis or eczema.
Wood’s light examination revealed green
fluorescence in 4 cases.
M. canis was the pathogen, isolated on
fungal culture in all 9 patients. The upper
surface of colony revealed whitish hue
while yellow pigment was seen on reverse
side (Figure 2). Teased mounts of a
125
Table 1 Demographic and clinical data of patients (n=9)
Sr. No.
Age (yrs)
Sex
Duration of Clinical
disease
variety
(mo)
1.
7
M
4
G
2.
6
M
6
A
3.
10
F
2
A
4.
8
F
6
A
5.
12
M
3
G
6.
7
M
4
A
7.
6
F
5
G
8.
7
F
2
G
9.
6.5
F
3
A
M=male, F=female; G=grey patch, A=agminate folliculitis
mature colony stained with lactophenol
Wood’s lamp
examination
Fungus
culture
+
+
+
+
-
M. canis
M. canis
M. canis
M. canis
M. canis
M. canis
M. canis
M. canis
M. canis
desquamation, pustules and pruritus was
noted during the third week of treatment
Figure 3 Spindle-shaped macroconidia
(lactophenol cotton blue mount)
Figure 1 Agminate folliculitis
Figure 2 Colony of M. canis
cotton blue, revealed
macroconidia (Figure 3).
spindle-shaped
A reduction in the severity of erythema,
and the improvement continued until the
end of treatment and during the follow-up
period. Hair loss was not improved at 8
weeks but some regrowth of hair was seen
at 12 weeks (4 weeks after the completion
of therapy) in the follow-up period and
continued slowly at 16 weeks’ final
evaluation (8 weeks after the end of
therapy). Clinical cure was seen in 77.7%
cases and mycological cure was noted in
88.8% patients at 8 weeks time while
clinical cure was 89% and mycological
cure was 100% at final evaluation. One
patient developed mild headache while
another complained of nausea after intake
of griseofulvin which settled after the
completion of medication. Griseofulvin
treatment was well tolerated and the
adverse events were of mild intensity and
reversible nature.
126
Discussion
Tinea capitis is a common pediatric scalp
dermatophytosis.6,7 Topical therapy alone
is ineffective and systemic antifungal
agents are the mainstay of treatment.8,9
Griseofulvin, still ‘the gold standard
therapy’ is being used in many countries
due to its good efficacy, cost effectiveness
and less number of hazards.9,10 The new
antimycotic agents like terbinafine,
itraconazole and fluconazole are effective
alternatives but costly and beyond the
reach of most patients in Pakistan.
2.
M. canis is a zoophilic fungus which
causes grey patch, kerion and agminate
folliculitis type of tinea capitis1-3 and the
history of animal exposure in four of our
patients reflects animal host for this
species.
6.
3.
4.
5.
7.
8.
Our results showed clinical cure in 89%
patients and mycological cure in 100%
cases at final evaluation with griseofulvin
therapy, comparable with the results of
similar studies.10,11 The clinical parameters
noted were improved except the hair loss
because a longer period is required for hair
regrowth.12-14 In our opinion griseofulvin
which is the cheapest of systemic
antifungals has shown good antimycotic
and antiinflammatory response7 in this
zoophilic infection similar to the studies
which reveal that Microsporum scalp
infections are better treated with
griseofulvin rather than new antifungal
drug like terbinafine, a better choice for
Trichophyton scalp infections.6,15
In conclusion, the present study showed
griseofulvin to be effective, well-tolerated
and safe therapy for tinea capitis caused by
M. canis in our scenario.
References
1.
9.
10.
11.
12.
13.
14.
15.
Hay RJ, Moore M. Mycology. In:
Champion RH, Burton JL, Burns DA,
Breathnach SM, eds. Textbook of
dermatology, 6th edn. Oxford: Blackwell
Science; 1998. p. 1277-1376.
Martin AG, Kobayashi GS. Superficial
fungal infection: dermatophytosis, tinea,
nigra, piedra. In: Freedberg IM, Eisen AZ,
Wolff K et al., eds. Dermatology in
general medicine, 5th edn. New York:
McGraw-Hill; 1999. p. 2373-88.
Hussain I, Aman S, Haroon TS et al.
Tinea capitis in Lahore, Pakistan. Int J
Dermatol 1994; 33: 255-7.
Aman S, Hussain I, Haroon TS. Tinea
capitis: still no change in the etiological
spectrum of disease in our scenario. J Pak
Assoc Dermatol 2002; 12: 119-21.
Koumantaki E, Georgalla S, Rallis E,
Papadavid E. Doubled dose of oral
terbinafine is required for Microsporum
canis tinea capitis. Pediatr Dermatol
2001; 18: 60-2.
Becker LE. Griseofulvin: symposium on
superficial fungal infections. Dermatol
Clin 1984; 2: 115-28.
Higgins EM, Fuller LC, Smith CH.
Guidelines for the management of tinea
capitis. Br J Dermatol 2000; 143: 53-8.
Bennett ML, Fleischer AB, Loveless JW,
Feldman SR. Oral griseofulvin remains
the treatment of choice for tinea capitis in
children. Pediatr Dermatol 2000; 17: 3049.
Lopez-Gomez S, Del Palacio A, Van
Cutsem J et al. Itraconazole versus
griseofulvin in the treatment of tinea
capitis: a double-blind randomized study
in children. Int J Dermatol 1994; 33: 7437.
Elewski B. Treatment of tinea capitis
beyond griseofulvin. J Am Acad Dermatol
1999; 40: S27-30.
Rademaker M, Havill S. Griseofulvin and
terbinafine in the treatment of tinea capitis
in children. N Z Med J 1998; 111: 55-7.
Haroon TS, Hussain I, Aman S et al. A
randomized double-blind comparative
study of terbinafine and griseofulvin in
tinea capitis. J Dermatol Treat 1995; 6:
167-9.
Dragos V, Lunder M. Lack of efficacy of
6-week treatment with oral terbinafine for
tinea capitis due to Microsporum canis in
children. Pediatr Dermatol 1997; 14: 468.
Ormerod AD. What is new in therapy? Br
J Dermatol 2001; 145: 691-95.
Elewski B. Tinea capitis. Dermatol Clin
1996; 14: 23-31.
127
128
Original article
Lichen planus and hepatitis C virus infection: An
epidemiologic study
Tameez-ud-deen, Shahzana Naqqash, Abdul Quddus Butt.
Dermatology Department, Rawalpindi General Hospital, Rawalpindi
Abstract
Background Lichen planus is an immunologically mediated skin and mucous membrane
disease, which has been described in patients with hepatitis C virus-related liver disease, with
variable frequency.
Objective The purpose of this study was to determine the association of lichen planus with
hepatitis C virus related liver diseases.
Methods We tested sera of 55 patients with lichen planus for HCV antibodies by means of a
second generation enzyme linked immunosorbent assay. Serum levels of aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) were simultaneously
determined in all the patients. During the same period, a group of 110 patients admitted to the
Dermatology Department, RGH, Rawalpindi, served as a control.
Results Of the 55 patients with lichen planus, 18 had HCV antibodies (prevalence 32.7%), of
the 110 control patients 8 had HCV antibodies (prevalence 7.2%). There was significant
difference between the two groups. The ALT was raised in 21 patients with lichen planus,
and 15 of them also had an elevated AST level. In the control patients, the AST level was
raised in 4 of the 110 patients, 3 also had an elevated ALT level. The number of patients with
an abnormal transaminase level significantly differed in the two groups (38.1% in the lichen
planus group, and 4% in the control group).
Conclusion These results support a possible relationship between LP and chronic hepatitis C
and the hypothesis that LP may be associated with chronic liver diseases as a result of a
cytotoxic attack on the hepatocytes.
Key words
Lichen planus, hepatitis C virus
Introduction
Hepatitis C virus (HCV), identified in
1989, is an RNA virus that is a major
cause of acute and chronic hepatitis. Both
are asymptomatic in most patients,
however, chronic hepatitis C is a slowly
progressive disease and results in severe
morbidity in 20% of infected individuals.1
Majority of transfusion associated cases of
Address for Correspondence
Dr. Shahzana Naqqash
House No. 22, Ravi Road,
Wah Cantt, Punjab,
Pakistan.
hepatitis are due to HCV,2 as blood donors
are now screened for HCV antibodies, the
risk of post-transfusion hepatitis is
declining.3 Low level of sexual
transmission is also possible.4
According to WHO about 170 million
people i.e. 3% of the world’s population
are estimated to be infected with HCV
with prevalence of 0.5% to more than 10%
in population samples around the world.5
Prevalence of HCV infection varies from
129
4% to 7% in various segments of
Pakistan.6
Chronic hepatitis C is associated with a
variety of disorders, particularly as regards
dermatology. The most frequent of these
are
mixed
cryoglobulinemia
with
leukocytoclastic vasculitis, porphyria
cutanea tarda and lichen planus.1 In 1991
Mockni et al.7 described a patient in whom
lichen planus (LP) developed during
HCV-induced chronic hepatitis. Since then
numerous cases of HCV-associated LP
have been published, and association of
chronic hepatitsis with lichen planus has
been established, especially in Italian
patients.8 LP is considered by certain
authors as a possible marker of HCV
infection. The prevalence of HCV
infection in patients with LP varies
considerably from one geographic area to
another, ranging from 4% in northern
France9 to 62% in Japan.10 On the other
hand, studies from Great Britain have
failed to reveal any association. Similarly
another study from France by Cribier et
al.11 found no difference with regard to
HCV prevalence in patients with lichen
planus and in patients with other
dermatoses. However, Jubert et al.9
described six patients with lichen planus
and chronic HCV infection. Rebora12
reported that prevalence of HCV
antibodies was 14% in 87 patients with
lichen planus.
We describe the prevalence of HCV
antibodies in a group of 55 patients in a
case-controlled study.
Patients and methods
Between January, 2002 and February,
2003, 55 patients with lichen planus were
diagnosed on the basis of usual clinical
features and specific histologic findings.
Patients suspected of drug-induced
lichenoid eruption were not included.
There were 22 women, 16-75 years of age
(average 43), and 33 men aged 11-55
years (average 52.8). Of the 55 patients,
19 had erosive lichen planus of the mouth,
while 3 had associated genital lesions.
During the same period, a group of 110
patients presented to the dermatology
department for various dermatological
diseases excluding lichen planus served as
control. The group included 60 females 780 years (average 37.5) of age, 40 males
12-60 years of age (average 51.5).
Sera from all the patients were tested for
HCV antibodies by means of secondgeneration enzyme-linked immunosorbent
assay. The serum levels of aspartate
aminotransferase (AST) and alanine
aminotransferase
(ALT)
were
simultaneously determined in all patients.
The modified chi square test was used for
statistical comparison of the two groups.
Results
The number of male patients with lichen
planus was significantly higher than the
control group. The age of male patients
did not differ in the two groups, whereas
the age of female patients with lichen
planus was higher than in the control
group. Of the 55 patients with lichen
planus, 18 had HCV antibodies
(prevalence 32.7%), of the 100 control
patients 7 had HCV antibodies (prevalence
7%). There was significant difference
between the two groups. The ALT was
raised in 21 patients with lichen planus,
and 15 of them also had an elevated AST
level. In the control patients, the AST level
was elevated in 4 of the 100 patients, 3
also had an elevated ALT level. The
number of patients with an abnormal
transaminase level significantly differed in
130
the two groups (38.1% in the lichen planus
group, and 4% in the control group).
Discussion
A
frequent
occurrence
of
liver
abnormalities has been reported in patients
with lichen planus.13,14 Chronic active
hepatitis especially due to hepatitis C virus
is suspected to be a contributing factor.
Significant association of erosive lichen
planus with chronic hepatitis was
demonstrated in a case controlled study.15
Recently this association between lichen
planus and liver disease has been
questioned. A study in 180 English
patients with oral lichen planus failed to
show any significant association with liver
dysfunction.16 Similarly no difference was
found with regard to HCV antibodies
prevalence in patients with lichen planus
and in patients with other dermatoses by
Bernard et al.11 in 1992. The prevalence of
HCV in patients with lichen planus varies
considerably from one geographic area to
another, ranging from 4% in France9 to
62% in Japan.10 In our study a strong
association between lichen planus and
HCV infection was revealed. The
prevalence of HCV infection in our
community ranges between 3-7%.6 In our
patients with lichen planus the HCV
prevalence of 32.7% cannot be a chance
association. In patients with lichen planus
HCV may be etiologically related, and
these patients should have assessment of
liver function for early detection and
prevention of possible liver damage.
References
1.
2.
Bonkovsky, HL, Mehta S. Hepatitis C: a
review and update. J Am Acad Dermatol
2001; 44: 150- .
Vrielink H, Vander Poel CL, Reesnik HW
et al. Look-back study of infectivity of
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
anti-HCV
ELISA-positive
blood
components. Lancet 1995; 345: 95-6.
Donahue JG, Alvaro M, Ness PM et al.
The declining risk of post-transfusion
hepatitis C virus infection. N Engl J Med
1992; 327: 369-73.
Gabrielli C, Zannini A, Corradini R et al.
Spread of hepatitis C virus among sexual
partners HCVab positive intravenous drug
users. J Infect Dis 1994; 29: 17-22.
World Health Organization. Hepatitis C:
global prevalence. Epidemiol Rep 1997;
45: 341-8.
Umar M, Bushra HT, Shuaib A et al.
Spectrum of chronic liver disease due to
hepatitis C virus infection. J Coll Phys
Surg Pak 2000; 10: 380-3.
Mokni M, Rybojad M, Puppin D Jr et al.
Lichen planus and hepatitis C virus. J Am
Acad Dermatol 1991; 24: 792.
Gruppo Italiano Sudi Epidermiologici in
Dermatologia (GISED). Lichen planus
and liver disease: a multicentre casecontrolled study. BMJ 1990; 300: 227-30.
Jubert C, Pawlotsky JM, Pouget F et al.
Lichen planus and hepatitis C virusrelated chronic active hepatitis. Arch
Dermatol 1994; 130: 73-6.
Nagao Y, Sata M, Tanikawa K et al.
Lichen planus and hepatitis C virus in
northern region of Japan. Eur J Clin Invest
1995; 25: 910-4.
Cribier B, Garnier C, Laustriat D, Heid E.
Lichen planus and hepatitis C virus
infection: an epidemiologic study. J Am
Acad Dermatol 1994; 31: 1070-2.
Rebora A. Lichen planus and the liver. Int
J Dermatol 1992; 3: 392-5.
Doutre MS. Hepatitis C virus-related skin
disease. Arch Dermatol 1999; 135: 14013.
Tanei R, Watanabe K, Nishiyama S.
Clinical and histopathologic analysis of
the Relationship between lichen planus
and chronic hepatitis C. J Dermatol 1995;
22: 316-23.
Mignogna MD, Muzio LL, Favia G et al.
Oral lichen planus and HCV infection: a
clinical evaluation of 263 cases. Int J
Dermatol 1998; 37: 575-8.
El–Kabir M, Scully C, Porter S et al.
Liver function in UK patients with oral
lichen planus. Clin Exp Dermatol 1993;
18: 12-16.
131
Review article
Zinc: An overview and therapeutic uses in
dermatology
Arfan-ul-Bari, *Simeen Ber Rehman
PAF Hospital, Sargodha
*Dermatology Department, Military Hospital, Rawalpindi
Abstract
Zinc is an essential component of various important enzymes in our body and its
deficiency causes multi-enzyme defects and multisystemic disease. It ranks with biotin
as a truly essential element in both cutaneous health and disease. Zinc deficiency may
explain alopecia, ulcers, infections and a host of strange unexplainable skin changes.
Introduction
Zinc is an essential mineral that is found in
almost every cell. It stimulates the activity
of approximately 100 enzymes, which are
substances that promote biochemical
reactions in the body.l,2 It must be obtained
from the diet since the body cannot make
enough. Next to iron, it is the most
abundant trace mineral in the body. It is
stored primarily in muscles, but is also
found in high concentrations in red and
white blood cells, the retina of the eye,
bones, skin, kidneys, liver, and pancreas.
In men, the prostate gland stores high
amounts of it. Zinc plays an important role
in the immune system and is helpful in
protecting against infection,3,4 is needed
for wound healing,5 helps maintain the
sense of taste and smell,6 and is needed for
DNA synthesis.2 Zinc also supports
normal growth and development during
pregnancy, childhood, and adolescence.7,8
Zinc also has some antioxidant properties,9
which means that it helps protect cells in
Address for Correspondence
Squadron Leader Dr. Arfan-ul-Bari
Consultant Dermatologist
PAF Hospital, Sargodha.
Ph# 051-561-33799, 5583688
Email: albariul@yahoo.com
the body from the potential damage caused
by free radicals. Free radicals are believed
to contribute to the aging process. The
typical daily intake of zinc in the Western
diet is approximately 10 mg, two thirds of
the recommended dietary allowance
(RDA).2 Low zinc intake is often seen in
the elderly, alcoholics, people with
anorexia, and individuals on restrictive
weight loss diets.2 Zinc deficiency can also
be caused by diseases that interfere with
the absorption of nutrients from food, such
as irritable bowel disease, celiac disease,
and chronic diarrhea.10,11 Some of the
symptoms of zinc deficiency include loss
of appetite, poor growth, weight loss,
impaired taste or smell, poor wound
healing, skin abnormalities (such as acne,
atopic dermatitis and psoriasis), hair loss,
lack of menstrual period, night blindness,
hypogonadism and delayed sexual
maturation, white spots on the fingernails
and feelings of depression.2,10,12-14 The body
absorbs 20% to 40% of the zinc present in
food. Dietary fiber, particularly phytates,
can interfere with the body's ability to
absorb zinc. Zinc is best absorbed when
taken with a meal that contains protein.15
The best sources of zinc are oysters
(richest source), beef, liver, pumpkin
132
seeds, pecans, poultry, cheese (ricotta,
Swiss, gouda), shrimp, crab, and other
shellfish. Other good, though less easily
absorbed sources of zinc include legumes
(especially lima beans, black-eyed peas,
pinto beans, soybeans, peanuts), whole
grains, miso, tofu, brewer's yeast, cooked
greens, mushrooms, green beans, tahini,
and pumpkin and sunflower seeds.16-18
Zinc sulfate is the most frequently used
supplement. This is the least expensive
form, but it is the least easily absorbed and
may cause stomach upset. Health care
providers usually prescribe 220 mg zinc
sulfate, which contains approximately 55
mg of elemental zinc.15 The more easily
absorbed forms of zinc are zinc picolinate,
zinc citrate, zinc acetate, zinc glycerate,
and zinc monomethionine. If zinc sulfate
causes stomach irritation, another form
such as zinc citrate should be tried.15,19
Zinc should be taken with water or juice.
However, if zinc causes stomach upset, it
can be taken with meals. It should not be
taken at the same time as iron or calcium
supplements.20 A strong relationship exits
between zinc and copper. Too much of
one can cause a deficiency of the other.
Long-term use of zinc (including zinc in a
multivitamin) should be accompanied by
copper. For every 15 mg of zinc include 1
mg of copper. Daily intakes of dietary
zinc, according to the US RDA, are:
infants and children up to 3 years: 2 - 3 mg
(RDA); children 4 to 8 years: 5 mg
(RDA); children 9 to 13 years: 8 mg
(RDA); males 14 to 18 years: 11 mg
(RDA); females 14 to 18 years: 9 mg
(RDA); pregnant females 19 years and
older: 11 mg (RDA); breastfeeding
females: 12 -14 mg (RDA).2
Therapeutic range of elemental zinc in
men is 30 to 60 mg daily and in women is
30 to 45 mg daily. Doses over the amounts
listed should be limited to only a few
months under the supervision of a
healthcare professional. Research has
shown that less than 50 mg a day is a safe
amount to take over time, but researchers
are not sure what happens if more is taken
over a long period. Taking more than 150
mg per day may interfere with the body's
ability to use other minerals.2,15 Common
side effects of zinc include stomach upset,
nausea, vomiting, and a metallic taste in
the mouth. Other reported side effects of
zinc toxicity are dizziness, headache,
drowsiness, increased sweating, loss of
muscle coordination, alcohol intolerance,
hallucinations, and anemia.21 High doses
of zinc may also lower HDL ("good")
cholesterol and raise LDL ("bad")
cholesterol. This may be due to a copper
deficiency brought on by the long-term
use of zinc.22 Zinc can have interactions
with drugs like ACE inhibitors,
quinolones,
tetracycline,
hormone
replacement therapy (HRT), hydralazine,
immunosuppressants,
nonsteroidal
anti-inflammatory drugs (NSAIDs) and
penicillamine.23-27
Therapeutic uses in dermatology
Infections
Zinc is required for the development and
activation of T-lymphocytes, a kind of
white blood cell that helps fight infection.2
People who are zinc deficient tend to be
more susceptible to a variety of infections.
Zinc supplementation enhances immune
system activity and protects against a
range of infections including upper
respiratory tract infections, skin and
mucocutaneous infections.28-33
HIV / AIDS
Zinc deficiency is common in people with
HIV (even before symptoms appear) or
AIDS. Zinc deficiency leads to increased
susceptibility to opportunistic infections in
people with AIDS. When studied, zinc
supplementation has increased CD4
133
counts.34
Burns
When skin is burned, a substantial
percentage of micronutrients, such as
copper, selenium, and zinc may be lost.
This increases the risk for infection, slows
the healing process, prolongs the hospital
stay, and even increases the risk of death.
Although
it
is
unclear
which
micronutrients are most beneficial for
people with burns, many experts suggest
that a multivitamin containing zinc and
other vital nutrients be included in the
therapy to aid recovery.35
Acne
There is some evidence that zinc
supplementation (such as zinc gluconate)
reduces acne inflammation. Studies to date
have had certain limitations, however.
Therefore, it is difficult to draw definite
conclusions about how much zinc to use,
what type of zinc is best, and the duration
of treatment. Antibiotics such as
erythromycin and tetracyclines are
sometimes combined with zinc in topical
preparations for inflammatory acne. It is
unclear whether zinc enhances the effects
of the antibiotics or simply serves as a
mode of delivery for the antibiotics.36-41
Herpes simplex
Topical preparations of zinc have shown
benefit in relieving symptoms and
preventing recurrences of oral herpes
lesions (canker sores).42
Acrodermatitis enteropathica
Zinc
dramatically
reverses
the
manifestations within hours to days in
patients with acrodermatitis enteropathica
(a skin disorder that is due to an inherited
inability to absorb zinc properly; generally
affects the limbs, mouth, or anus and may
include hair loss and diarrhea.43-45
Skin wounds and ulcers
Zinc supplements are often given to help
heal skin ulcers or bed sores but they do
not increase rates of wound healing when
zinc levels are normal.2,46
Conclusion
Zinc is a truly essential element required
for a normal functioning healthy skin and
it has a definite role in treating a variety of
dermatological disorders. It pays to think
zinc when looking at a strange dermatitis.
Before ordering a plasma level
determination, be sure that rubber stoppers
are not used and specimen does not
hemolyze because red cells and rubber
stoppers are zinc rich.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
Sandstead HR. Understanding zinc: recent
observations and interpretations. J Lab
Clin Med 1994; 124: 322-7.
Institute of Medicine. Food and Nutrition
Board. Dietary Reference Intakes for
Vitamin A, Vitamin K, Arsenic, Boron,
Chromium,
Copper,
Iodine,
Iron,
Manganese,
Molybdenum,
Nickel,
Silicon, Vanadium, and Zinc. Washington,
DC: National Academy Press, 2001.
Solomons NW. Mild human zinc
deficiency produces an imbalance between
cell-mediated and humoral immunity.
Nutr Rev 1998; 56: 27-8.
Prasad AS. Zinc: an overview. Nutrition
1995; 11: 93-9.
Heyneman CA. Zinc deficiency and taste
disorders. Ann Pharmacother 1996; 30:
186-7.
Prasad AS, Beck FW, Grabowski SM et
al. Zinc deficiency: changes in cytokine
production and T-cell subpopulations in
patients with head and neck cancer and in
noncancer subjects. Proc Soc Am
Physicians 1997; 109: 68-77.
Simmer K, Thompson RP. Zinc in the
fetus and newborn. Acta Paediatr Scand
Suppl 1985; 319: 158-63.
Fabris N, Mocchegiani E. Zinc, human
diseases and aging. Aging (Milano) 1995;
7: 77-93.
Anderson RA, Roussel AM, Zouari N et
al. Potential antioxidant effects of zinc
134
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
and chromium supplementation in people
with type 2 diabetes mellitus. J Am CoIl
Nutr 2001; 20: 212-8.
Hambidge KM. Mild zinc deficiency in
human subjects. In: Mills CF, ed. Zinc in
human biology. New York: SpringerVerlag; 1989. p. 281-96.
Naber TH, van den Hamer CJ,
Baadenhuysen H, Jansen JB. The value of
methods to determine zinc deficiency in
patients with Crohn’s disease. Scand J
Gastroenterol 1998; 33: 514-23.
King JC, Keen CL. Zinc. In: Shils ME,
Olson JA, Shike M, Ross AC, eds.
Modern nutrition in health and disease,
9th edn. Baltimore: Williams & Wilkins;
1999. p. 223-39.
Ploysangam A, Falciglia GA, Brehm BJ.
Effect of marginal zinc deficiency on
human growth and development. J Trop
Pediatr 1997; 43: 192-8.
Nishi Y. Zinc and growth. J Am Coll Nutr
1996; 15: 340-4.
Gordon KF, Gordon RC, Passal DB. Zinc
metabolism: basic, clinical, and behavioral
aspects. J Pediatr 1981; 9: 341-9.
Murray MT. The healing power of foods.
Rocklin: CN Prima Publishing; 1993.
US
Department
of
Agriculture,
Agricultural Research Service, 2001.
United States Department of Agriculture
Nutrient Database for Standard Reference,
Release 14. Nutrient Data Laboratory
Home
Page,
http://www.nal.usda.gov/fnic/foodcomp.
Dietary Guidelines Advisory Committee,
Agricultural Research Service, United
States
Department
of
Agriculture
(USDA). HG Bulletin No. 232, 2000.
Sandstrom B. Bioavailability of zinc. Eur
J Clin Nutr 1997; 51 (Suppl 1): SI7-S19.
Whittaker P. Iron and zinc interactions in
humans. Am J Clin Nutr 1998; 68: 442S446S.
Lewis MR, Kokan L. Zinc gluconate:
acute ingestion. J Toxicol Clin Toxicol
1998; 33: 99-101.
Hooper PL, Visconti L, Garry PI, Johnson
GE. Zinc lowers high-density lipoprotein
cholesterol levels. J Am Med Assoc 1980;
244: 1960-1.
Brouwers JR. Drug interactions with
quinolone antibacterials. Drug Saf 1992;
7: 268-81.
Dendrinou-Samara
C,
Tsotsou G,
Ekateriniadou E et al. Anti-inflammatory
drugs interacting with Zn(II), Cd(II) and
Pt(II) metal ions. J Inorg Biochem 1998;
71: 171-9.
Golik A, Zaidenstein R, Dishi V et al.
26.
27.
28.
29.
30.
31.
32.
Effects of captopril and enalapril on zinc
metabolism in hypertensive patients. J Am
Col1 Nutr 1998; 17: 75-8.
Neuvonen PJ. Interactions with the
absorption of tetracyclines. Drugs 1976;
11: 45-54.
Otomo S, Sasajima M, Ohzeki M, Tanaka
I. Effects of D-penicillamine on vitamin
B6 and metal ions in rats [in Japanese].
Njppon Y Agurigaku Zsshi 1980; 76: 1-13.
Fortes C, Forastiere F, Agabiti N et al.
The effect of zinc and vitamin A
supplementation on immune response in
an older population. J Am Geriatr Soc
1998; 46: 19-26.
Garland ML, Hagmeyer KO. The role of
zinc lozenges in treatment of the common
cold. Ann Pharmacother 1998; 32: 63-9.
Girodon F, Lombard M, Galan P et al.
Effect of micronutrient supplementation
on infection in institutionalized elderly
subjects: a controlled trial. Ann Nutr
Metab 1997; 41: 98-107.
Prasad AS, Beck FW, Kaplan J et al.
Effect of zinc supplementation on
incidence of infections and hospital
admissions in sickle cell disease (SCD).
Am J Hematol 1999; 61:194-202.
Shankar AH, Prasad AS. Zinc and
immune function: the biological basis of
altered resistance to infection. Am J Clin
Nutr 1998; 68: 447S-63S.
33. Black RE. Therapeutic and preventive
effects of zinc on serious childhood
infectious
diseases
in
developing
countries. Am J Clin Nutr 1998; 68: 476S79S.
34. Beck FW, Prasad AS, Kaplan J et al.
Changes in cytokine production and T cell
subpopulations in experimentally induced
zinc-deficient humans. Am J Physiol 1997;
272: E1002-7.
35. De-Souza
DA,
Greene
LJ.
Pharmacological nutrition after burn
injury. J Nutr 1998; 128: 797-803.
36. Dreno B, Amblard P, Agache P et al. Low
doses of zinc gluconate for inflammatory
acne. Acta Derm Venereol 1989; 69: 5413.
37. Dreno B, Trossaert M, Boiteau HL, Litoux
P. Zinc salts effects on granulocyte zinc
concentration and chemotaxis in acne
patients. Acta Derm Venereol 1992; 73:
250-2.
38. Krowchuk DP. Treating acne. A practical
guide. Med Clin North Am 2000; 84: 81128.
39. Meynadier 1. Efficacy and safety study of
two zinc gluconate regimens in the
treatment of inflammatory acne. Eur J
135
Dermatol 2000; 10: 269-73.
40. Papageorgiou PP, Chu AC. Chloroxylenol
and zinc oxide containing cream (Nels
cream®) vs. 5% benzoyl peroxide cream
in the treatment of acne vulgaris. A
double-blind, randomized, controlled trial.
Clin Exp Dermatol 2000; 25: 16-20.
41. Toyoda M, Morohashi M. An overview of
topical antibiotics for acne treatment.
Dermatology 1998; 196: 130-4.
42. Godfrey HR, Godfrey NJ, Godfrey JC,
Riley D. A randomized clinical trial on the
treatment of oral herpes with topical zinc
oxide/glycine. Altern Ther Health Med
2001; 7: 49-56.
43. Walravens FA, Hambidge KM, Neldner
KH. Zinc metabolism in acrodermatitis
enteropathica. J Pediatr 1978; 93: 71-3.
44. Der Kaloustian VM, Musallam SS, Sanjad
SA et al. Oral treatment of acrodermatitis
enteropathica with zinc sulfate. Am J Dis
Child 1976; 130: 421-3.
45. Leupold D, Poley JR, Meigel WN. Zinc
therapy in acrodermatitis enteropathica.
Helv Paediatr Acta 1976; 31: 109-15.
46. Anderson I. Zinc as an aid to healing.
Nurs Times 1995; 91: 68-70.
136
Review article
Cockayne syndrome. An update.
Farhana Muzaffar, *Ijaz Hussain
Department of Pediatric Dermatology, Institute of Child Health/Children Hospital,
Lahore
* Department of Dermatology, King Edward Medical College/Mayo Hospital, Lahore
Abstract
Cockayne’s syndrome is a rare heterogeneous autosomal recessive disorder with poor
genotype-phenotype correlation. The basic underlying abnormality in CS is defective
transcription-coupled repair of DNA whereas the global genome repair pathway of
nucleotide-excision repair is normal. Clinically the spectrum of CS spans from
classical type (CS type 1, CKN1, CSA), a more severe form with symptoms present at
birth (CS type 2, CSB, also known as cerebro-oculo-facial syndrome and Pena-Shokeir
type II syndrome), a milder form (CS type 3), and xeroderma pigmentosum-Cockayne
syndrome (XP-CS). However, CS type 1 and CS type 2 are the major phenotypes. The
cardinal features of CS are growth failure, premature aging, and pigmentary retinal
degeneration along with a number of nonspecific clinical findings. The definite
diagnosis requires assay of DNA repair in skin fibroblasts or lymphoblasts. Prenatal
diagnosis is also possible at 16-18 weeks of gestation. There is progressive downhill
course with premature death before adulthood. Besides genetic counselling a
multidisciplinary approach is required.
Introduction
Cockayne’s syndrome (CS); also called
Neill-Dingwall syndrome, progeria-like
syndrome and progeroid nanism; belongs to
a group of inherited disorders with
heterogeneous clinical features which have
in vitro or in vivo cellular hypersensitivity to
damage by certain physical or chemical
agents. These diseases include xeroderma
pigmentosum (XP), Cockayne syndrome,
trichothiodystrophy
(TTD),
Bloom
syndrome, Fanconi anemia, dyskeratosis
congenita, basal cell nevus syndrome,
ataxia-telangiectasia, and familial melanoma
with dysplastic nevi.1 Clinically, the
cutaneous, ocular, nervous, immune,
Address for Correspondence
Dr. Farhana Muzaffar
Assistant Professor
Department of Paediatric Dermatology
Institute of Child Health/ Children Hospital
Lahore
hemopoietic, skeletal, or gastrointeinal
systems are affected. Some are associated
with increased incidence of neoplasia. There
may be a progressive deterioration of body
functions. The cellular hypersensitivity is
helpful in the diagnosis, understanding the
pathogenic mechanisms and devising
therapeutic or prophylactic intervention. The
molecular
basis
of
the
cellular
hypersensitivity has been explored in some
of these disorders. This review focuses on
the clinical features and laboratory
abnormalities of CS.
History
The syndrome was described first by
Edward Alfred Cockayne, a British
pediatrician in 1936.2 His patient had
cachectic
dwarfism,
deafness,
and
pigmentary retinal degeneration with a
characteristic “salt and pepper” appearance
137
of the retina. The skin had photosensitivity
without
the
excessive
pigmentary
abnormalities seen in XP. There was marked
loss of subcutaneous fat, resulting in a
“wizened” appearance with typical “birdheaded” facies and prominent “Mickey
Mouse” ears. Other ocular findings included
cataracts and optic atrophy. Later, Catherine
M. Neill and Mary M. Dingwall3 reported
similar cases in 1950. Since then many cases
have been recognized and published in the
literature. A review published in 1992
described 140 cases reported in the
literature.4
Prevalence
The exact prevalence is not known as
essentially all cases have been reported as
single cases or family reports. The figure
generally used for rare diseases is 1/100,000
but CS occurs even less frequently than
this.5 The reported frequency in United
States6 is less than 1/250,000. CS has been
reported to be more common in isolated or
inbred communities.
CS affects all races without any sex
predilection.6 As it is a genetic disorder the
manifestations may be delayed until early
childhood.
Etiology
CS is an autosomal recessive disorder. The
basic defect is the slow transcriptioncoupled DNA repair whereas the global
genome repair pathway of nucleotideexcision repair mechanism is intact.7
Complementation groups in CS [5,6,8]
On the basis of underlying genetic, CS has
two complementation groups, CS type 1
(CSA) and CS type 2 (CSB) due to defect in
ERCC8 and ERCC6 genes, respectively.
Table 1 The underlying molecular genetic
defects in Cockayne’s syndrome [5]
CKN1, CSA
Gene
CSA gene
ERCC8
CS type
CSB
CSB gene
ERCC6
Gene locus
5
MIM 216400
10q11
MIM 133540
Frequency
25% of cases
75% of cases
Product
Cockayne
syndrome
WD-repeat
protein (CSA
protein)
396
amino
acids
44 kDa
Excision
repair protein
ERCC6
(CSB protein)
Point
mutation
Deletion
ERCC8
Missense
mutation
Insertion
deletion
ERCC6
Types of
mutation
of
1349
acids
2,
amino
of
ERCC=excision repair cross-complementig
group, MIM=Mendelian inheritance in man
Both ERCC8 and ERCC6 transcribe to two
proteins CSA and CSB, respectively. Wild
CSA and CSB proteins remove the stalled
polymerase in such a way that the lesion
becomes accessible to repair enzymes. The
mutated proteins are deficient in their
function. However, the genotype-phenotype
relation is not absolute. The involved genes,
their respective loci and product are shown
in Table 1.
Cellular and molecular genetic overlap in
CS, XP, and TTD [8,9]
CS, XP, and TTD share common etiology
i.e. defective nucleotide excision repair
(NER). It is a complex mechanism to repair
DNA and hence to protect the genome
against injury induced by numerous
mutagenic
and
carcinogenic
agents
138
steps involved are, a) recognition of DNA
lesion, b) removal of the damaged
oligonucleotide, c) gap filling by DNA
synthesis, and d) ligation.
NER further comprises of two pathways.
One is the more rapid, transcription-coupled
repair (TCR) of expressed genes, targeted to
the transcribed strand. The other is slower,
global genome repair (GGR) of DNA, which
includes repair of the nontranscribed strand
of expressed genes and the inactive
chromatin.
Figure 1 Model showing two pathways of NER
i.e. global genome repair (left side) and
transcription-coupled repair (right side) [10].
Figure 2 Suggested hypothesis of TFIIH
dysfunction can lead to XP, CS and TTD [10].
e.g. photoproducts, chemical-produced
adducts, intrastrand crosslinks etc. Different
Figure 1 shows both pathways of NER. In
GGR (left part), the complex XP-C/HR233B
binds to DNA lesions and attracts XP-A,
RPA (ssDNA binding protein) and then
TFIIH (recognition of DNA lesion). XP-E
protein facilitates the identification of
lesions which are poorly recognized by
XP-C/HR233B e.g. cyclobutane pyrimidine
dimers. Demarcation of the lesions is carried
out by XP-B and XP-D (two helicases) of
TFIIH followed by sequential cleavage by
two structure-specific nucleases XP-G (on
3’ side) and ERCC1-XP-F (on 5’ side)
[removal of damaged oligonucleotides].
After removal of an oligonucleotide
containing the lesion, DNA synthesis occurs
using either polymerase δ or ε in the
presence of PCNA and RF-C complexes as
processitivity factors (gap filling by DNA
synthesis). The final step is ligation of the
newly synthesized DNA patch to parental
strand by DNA ligase I.10
TCR differs from GGR in the initial step i.e.
recognition of lesion only (right half). On
damaged templates, RNA polymerase II is
blocked by the lesion inducing signal for
TCR. Proteins CSA, CSB, and possibly
139
XP-G and TFIIH displace the stalled RNA
poly II from the lesion. Now the lesion
becomes accessible for further repair in the
same way as for GGR.10
Transcription and DNA repair are two
closely associated processes. TFIIH is a
complex of 9 proteins which has dual role in
transcription and repair. It inhibits cell cycle
and transcription but induces TCR, DNA
repair, or apoptosis after genome damage. It
is speculated that CS, XP, or TTD are the
consequences of TFIIH dysfunction.
Mutations in one of the two DNA repair
genes in TFIIH may lead to three different
human disorders: a) XP (the skin cancerprone syndrome), b) CS or TTD alone, and
c) CS- or TTD-associated with XP in the
same patient (Figure 2). It is hypothesized
that some of DNA-repair deficient patients
may also have transcription deficiency. The
same gene defect can result in apparently
identical cellular phenotypes related to DNA
repair deficiency, yet give rise to completely
different clinical features.
Cellular hypersensitivity
Like XP, cultured cells (fibroblasts or
lymphocytes) from patients with CS are
hypersensitive to UV-induced inhibition of
growth and colony-forming ability.11 Host
cell reactivation of UV-damaged adenovirus
or plasmids is reduced, although to a lesser
extent than in XP.12 Increased mutation
frequency has been reported in circulating
lymphocytes from two donors with CS.13
Chromosome abnormalities
Chromosome karyotype and sister chromatid
exchange frequency is usually normal in
untreated cells but increase in sister
chromatid exchanges and a delayed recovery
Table 2 compares the laboratory
characteristics and main clinical features in
the three NER syndromes [10].
UV sensitivity
Residual UDS
TCR
GGR
Photosensitivity
Skin cancer
Progressive mental
degeneration
Neuronal loss
Neurodysmyelination
Thin facies
Growth defect
Hypogonadism
Brittle hair and nails
Ichthyosis
XP
+, ++
5%50%
↓
except
XP-C
↓
++
++
+/-
CS
+
1550%
↓
TTD
+
WT
WT
+a
-b
+
↓
+a
-b
+
+/+/+/-
+
+
+
+
+
-
+
+
+
+
+
+
+
↓
GGR=global genome repair, TCR=transcriptioncoupled repair, UDS=unscheduled DNA
synthesis, WT=wild type (control level),
+=present, ++=markedly present, +/-=sometimes
present, ↓=reduced, a=patients with CS and TTD
may have no photosensitivity, b=skin cancer
may be present in XP/CS or XP/TTD overlap
of chromosome damage is reported after
UVR exposure.11,14,15
Pathophysiology
Pathologic studies reveal diffuse and
extensive demyelinating in the central and
peripheral nervous systems. Patients
demonstrate pericapillary calcifications in
the cortex and basal ganglia at an early age.6
Severe neuronal loss in the cerebaral cortex
and cerebellum also occurs. These changes
correlate with the physiologic changes of
skin.
Clinical features [4,5,6]
With elucidation of molecular genetic
defects, it has been recognized that CS is not
a single phenotype but it spans a spectrum
140
that comprises: CS type 1, the classical
form; CS type 2, a more severe form with
symptoms present at birth, also called
connatal CS (previously called cerebrooculo-facial [COFS] syndrome and PenaShokeir type 2 syndrome; CS type 3, a
milder form; and xeroderma-pigmentosumCockayne syndrome (XP-CS). CS type 1
and CS type 2 are the two well-accepted
types.
CS type 1 (classical, CNK1, CSA)
Birth weight, length and head circumference
are normal. However, within the first two
years growth and development become
abnormal. There is delayed psychomotor
development, poor feeding, photosensitive
rashes and cataract. By the time the disease
becomes fully manifest, height, weight, and
head circumference are far below the fifth
percentile. The characteristic appearance of
a child with CS is a cachectic dwarf with
thinning of the skin and hair, sunken eyes,
and a stooped standing posture (Figure 3).
Different clinical signs and symptoms
reported in CS are enlisted in Table 3.
Progressive impairment of vision (due to
cataracts and pigmentary retinopathy),
sensorineural deafness, hypertension, joint
Figure 3 A girl showing typical facies of CS
with sunken eyes, beaked nose, large ears, and
frecles over face.
Table 3 Clinical signs/symptoms reported in
Cockayne syndrome [4,5,6].
 Neurologic
Increased tone/spasticity
Hyper- or hyporeflexia
Abnormal gait or inability to walk,
ataxia
Incontinence
Tremors
Abnormal speech or absence of speech,
seizures
Weak cry/poor feeding
Muscle atrophy
Behavioral abnormality
Seizures
 Dermatologic
Photosensitivity (~75%)
Malar rash
Xerosis
Mottled pigmentation and atrophic scars
Loss of subcutaneous fat
Premature aging
Anhidrosis
Thin, dry hair
 Ophthalmologic [16]
Pigmentary retinal degeneration/retinitis
pigmentosum (develops late) [~55%]
Cataract (before 3 years)[36%]
Miotic pupils
Farsightedness
Decreased or absent tears
Strabismus
Nystagmus
Photophobia
Narrowed retinal arterioles
Microcornea
Iris hypoplasia
Microphthalmia.
Optic atrophy
 Ears
Sensorineural deafness (mild-moderate)
[~66%]
 Dental
Caries (~86%)
Absent or hypoplastic teeth
Delayed eruption of deciduous teeth
Malocclusion
 Endocrinal
Undescented testes
Delayed/absent sexual maturation
Infertility
 Musculoskeletal
Skeletal dysplasia
Relatively long limbs
Contractures of hips, knees, ankles
141



Gastrointestinal
Elevated liver function tests
Hepatosplenomegaly
Renal [17]
Hypertension
Decreased creatinine clearance
Other
Reduced immunity to infections
contractures and ataxia lead to severe
disability. However, CS is not associated
with an increased incidence of neoplasia.
Death typically occurs in the first or second
decade as a result of pneumonia and other
respiratory infections. The mean age of
death is 12 years, but survival into third
decade has been reported.
CS type 2 (CSB)
Also called ‘connatal’ CS, is the severe form
of syndrome in which growth failure is
evident at birth and little or no postnatal
neurological
development
occurs.
Congenital cataracts or other structural
anomalies of the eye are reported in 30%.
Patients have arthrogryposis or early
contractures joints and spine (kyphosis,
scoliosis). Patients typically die by the age
of 7 years. This group overlaps clinically
with two other genetic disorders named, the
cerebro-oculo-facial syndrome (COFS) and
Pena-Shokeir type II syndrome. A mutation
in the ERCC6 gene has been reported in
COFS. It is now recognized that patients
previously labeled to have COFS or PenaShokeir type II syndrome, who have
molecular or biochemical evidence of
ERCC8
or
ERCC6
mutations
or
characteristic DNA repair abnormalities,
should be diagnosed as having Cockayne
syndrome type 2.
CS type 3
Before the discovery of molecular defects of
CS, a few cases with some features of CS
but with essentially normal growth and
cognitive development, or late onset, were
reported.18 These have been categorized as
CS type 3. The molecular defect in DNA
repair or protein complementation has not
been documented. In a single case clinically
resembling late-onset CS, an insertional
deletion of chromosome 10q21.1 has been
reported.
Xeroderma pigmentosum–Cockayne
syndrome complex
The correlation between genotype, cellular
phenotype, and clinical phenotype is not
absolute. A number of patients with CS have
been found to have, in addition, clinical
features of XP. These features include
freckling on sun-exposed skin and cutaneous
neoplasms. Cells from these XP/CS patients
have reduced DNA excision repair
characteristic of XP. Clinically, these
patients may be distinguished from XP
patients with neurologic abnormalities by
the presence of the CS features of
pigmentary
retinal
degeneration,
calcification of the basal ganglia, normalpressure hydrocephalus, and hyperreflexia.
Cells from patients with this complex have
been assigned to XP-B, -D, and -G,
complementation groups. The De-SanctisCacchione19
variant
of
xeroderma
pigmentosum includes some features of CS
such as mental retardation, spasticity, short
stature, and hypogonadism, but without
skeletal dysplasia, the facial phenotype of
CS,
or
CNS
demyelination
and
calcifications.
Diagnosis [4,5,6]
The characteristic features of syndrome may
not be evident and the diagnosis may be
delayed for years. Poor psychomotor
142
development, emergence of a typical
abnormality of CS e.g. blindness, deafness,
or extreme photosensitivity make parents
visit a physician. No consensus guidelines
have been developed whether CS should be
diagnosed exclusively on the basis of
clinical criteria, cellular phenotype, genetic
phenotype, or a combination of the three.
The syndrome is diagnosed by clinical
findings in classical cases and in nonclassical cases by assay of DNA repair in
skin fibroblasts or lymphocytes. Such testing
is available in a few clinical laboratories.
Clinical Diagnosis
Classical Cockayne syndrome (CS type 1)
The suggested diagnostic criteria for CS1
are given in Table 4. CS type 1 is suspected
in an older child when both major and three
minor criteria are present or in an infant or
toddler when both major and one minor
criterion along with abnormalities of DNA
repair are present.
Connatal Cockayne syndrome (CS type 2)
CS type 2 is suspected in infants with
growth failure at birth with little postnatal
increase in height, weight, or head
circumference.
1. Little or no postnatal neurological
development.
2. Congenital cataracts with other
structural defects of the eye
(microphthalmos, microcornea, iris
hypoplasia).
Laboratory findings [5,6]
Molecular genetic testing includes the
following test:
UV survival curve test
CS cells are abnormally sensitive to
ultraviolet radiation. Typically half to one-
Table 4: Suggested diagnostic criteria for CS
type 1 [5]
Major criteria
1. Height and weight below fifth
percentile for age and sex.
2. Developmental delay (absence or
delayed nervous system milestones e.g.
ability to speak or walk)
Minor criteria
1. Cutaneous photosensitivity with or
without thin or dry skin or hair.
2. Sensorineural deafness.
3. Pigmentary retinopathy and/or cataract.
4. Dental caries.
5. A characteristic physical appearance of
cachectic dwarfism with thinning of the
skin and hair, sunken eyes, and a
stooping posture, large for head size
ears ‘Mickey-mouse ears,’ small chin
with prominent, pointed ‘birdlike’ nose,
decreased facial subcutaneous adipose
tissue, microcephaly, an aged or
wizened facial appearance.
6. Demyelinating peripheral neuropathy (~
75%) diagnosed by electromyography,
nerve conduction testing, and/or nerve
biopsy.
7. Characteristic radiographic findings of
thickening of the calvarium, sclerotic
epiphyses,
vertebral
and
pelvic
abnormalities.
fourth as much as UVR kills majority of CS
cells (fibroblasts or lymphoblasts) as
compared to normal cells.
RNA synthesis inhibition assay
This test assesses the transcription-coupled
DNA repair. CS cells along with control
(cells from a normal person) are exposed to
UVR. RNA synthesis in CS cells is much
lower than normal cells due to their inability
to repair UVR-induced damage.
Complementation group testing
This test identifies whether a patient belongs
to CSA or CSB, seen in 25% and 75% of
patients, respectively. When fused together
and exposed to UVR, cells from different
143
groups having different genetic defect will
complement each other, showing enhanced
DNA repair. Currently complement testing
is more of research interest than of
immediate value to patient. Such testing
may be helpful, in future, to plan protein
therapy or gene therapy that is defective in a
patient.
Mutation analysis
This test is also of research interest. This
detects the type of mutation and the mutated
genes in a family.
Many other tests may be helpful in the
management. CT scan of brain shows
characteristic brain structural abnormalities
including calcium deposits in the basal
ganglia and normal pressure hydrocephalus
(ventricular
enlargement
without
obstruction). Magnetic resonance imaging
(MRI) of the brain shows atrophy and
dysmyelination of the cerebrum and
cerebellum. The electroencephalogram may
be abnormal, and x-ray examination may
show thickened skull and microcephaly.
Other tests may show sensorineural
deafness, neuropathica electromyogram, and
slow motor nerve conduction velocity. Bone
age is usually normal.
Prenatal Diagnosis
Prenatal diagnosis has been reported by
analysis of ultraviolet light sensitivity and
DNA repair in fetal cells obtained by
amniocentesis at 16-18 weeks gestation.
This test is still of research interest and not
offered clinically.21
Differential diagnosis [5,6]
The differential diagnosis of CS depends on
the presenting features of the particular
patient.
Abnormalities
that
suggest
alternative diagnoses are congenital
anomalies of the face, limbs, heart, or
viscera, recurrent infections other than otitis
media or respiratory infections; metabolic or
neurologic crises; hematologic abnormality
e.g. anemia, leuopenia; or malignancy of
any kind.
 Growth failure is a feature of many
chromosomal, endocrine, metabolic,
or
gastrointestinal
disorders
including malnutrition. Syndromes
with profound growth failure e.g.
Brachmann-de Lange, Duboitz,
Hallerman-Streiff,
RubinsteinTaybi, Russel-Silver, Seckel, and
Wiedemann-Rautenstrauch etc. can
usually be excluded on the basis of
physical appearance.
 In cases with photosensitivity or
thinning of the skin and hair, the
differential
diagnosis
includes
xeroderma pigmentosum, Bloom
syndrome,
Rothmund-Thompson
syndrome, and the premature aging
syndromes e.g. progeria, Werner
syndrome etc.
 Barring
Pelizaeus-Merabacher
disease, growth failure does not
occur in most leukodystrophies.
 The presence of calcification on
brain imaging might suggest
congenital infections e.g. rubella or
toxoplasmosis.
Management [5,6]
The management issues are, comprehensive
baseline evaluation and then serial
monitoring; symptomatic care; and genetic
counseling.
Baseline evaluation includes measurement
of growth, development assessment, dental
144
evaluation,
dermatologic
assessment,
ophthalmologic
evaluation
possibly
including electroretinogram, audiologic
evaluation including audiogram, brain MRI,
CT scan, EMG to document the presence of
demyelinating
neuropathy,
laboratory
studies to assess renal and hepatic function,
testing for diabetes mellitus or disorders of
calcium
metabolism,
and
skeletal
radiographs to document the skeletal
dysplasia. Patients should be followed up
and yearly assessed for known potential
complications e.g. hypertension, renal or
hepatic dysfunction, declining vision and
hearing.
CS children, despite their many problems,
are affectionate and cheerful. Nonetheless,
they need more attention because of their
physical and mental handicap. Families of
children with CS are under great stress due
to the need to provide extra attention,
medical emergencies due to complications
of CS, and financial burden. There is an
educational,
advocacy,
and
support
22
organization for helping patients with CS
and their families: The Share and Care
Cockayne Syndrome Network Box 552
Stanleytown, VA 24168Tel: 540-629-2369;
FAX: 540-647-3728
E-mail: cockayne@kimbanet.com
Symptomatic care should focus on an
individualized education program, assistive
devices, and safety in the home for
developmental delay and gait disturbances.
Regular physiotherapy may help prevent
contractures and maintain ambulation.
Feeding tube may be indicated, if feeding is
unsatisfactory, to prevent malnutrition.
Aggressive dental care, use of sunscreens
and avoidance of excessive sun exposure are
advisable. Specific problems may be
evaluated and treated by appropriate
specialists e.g. pediatricians, dermatologists,
ophthalmologists,
otolaryngologists,
audiologists, clinical geneticists and
rehabilitation therapists. These children may
benefit from special education including
sign language training, and from devices
such as ankle and foot orthotics to assist
walking, and hearing aids. From the
dermatologist viewpoint, children with CS
should avoid sun exposure though not such
strict protection is required as in XP.
Additional protection may be acquired by
use of protective clothing and sunblocks
with SPF ≥ 15.
It is also important to provide the patient and
family with information on the nature,
inheritance, and other implications of the
disease to help them make informed medical
and personal decisions. The parents of an
affected child are both obligate carriers of an
abnormal gene. The sibs of a proband have a
25% chance of being affected, a 50% chance
of being an ‘unaffected carrier’, and a 25%
chance of being normal. As this is a very
rare disorder, carriers can be counseled that
their chance of meeting another in the
general population is on the order of
1/5,000, and the chance of having an
affected child is one-quarter of that i.e.
1/20,000. Carrier testing can only be
performed by DNA analysis. Reproduction
has not been reported in any individual with
CS.
Prognosis
Patients with CS suffer a lot of morbidity
including neurological, dermatological,
ophthalmologic, dermatological, and otic
complications. The average life span in CS
is reported to be 12 years, though, the
145
severity of the genetic damage in the
affected individual and the food intake are
two important determinants. The oldest CS
patient is reported to be of 30’s. They end up
with premature death due to respiratory tract
infection.
Future prospects
It is hoped that the understanding of genes,
mutations and testing methodologies will
improve in future. As medical genetics and
bioengineering advances, gene therapy or
treatment with their products remains
another ray of hope for CS patients. DNA of
patients (extracted from leukocytes) should
be stored for future use.
9.
10.
11.
12.
References
1.
2.
3.
4.
5.
6.
7.
8.
Kraemer KH. Heritable diseases with
increased sensitivity to cellular injury. In:
Freedberg IM, Eisen AZ, Wolff K et al.,
eds. Dermatology in general medicine, 5th
edn. New York: McGraw-Hill; 1999. p.
1848-62.
Cockayne EA. Dwarfism with retinal
atrophy and deafness. Arch Dis Child 1936;
11: 148.
Neil C, Dingwall MM. A syndrome
resembling progeria. A review of two cases.
Arch Dis Child 1950; 11: 213-21.
Nance MA, Berry SA, Cock S. Review of
140 cases. Am J Med 1992: 42: 68-84.
Nance MA. Cockayne syndrome. Gene
Reviews [serial online] 2000. Available
from:
URL:
htt:www.geneclinics.org/servlet/access…/de
tails/htm.
Carter SM, Gross SJ. Cockayne syndrome.
eMed J [serial online] 2002; 3(4): [11
screens].
Available
from;
URL:
htt://www.emed.com/cgibin/foxweb.exe/screen.
Venema J, Mullenders LHF, Natarajan AT
et al. The genetic defect in Cockayne
syndrome is associated with a defect in
repair of UV-induced DNA damage in
transcriptionally active DNA. Proc Natl
Acad Sci USA 1990; 87: 4707-11.
Cleaver JE, Thompson LH, Richardson AS,
States JC. A summary of mutations in the
13.
14.
15.
16.
17.
18.
UV-sensitive
disorders:
xeroderma
pigmentosum, Cockayne syndrome and
trichothiodystrophy. Hum Mutat 1999; 14:
9-22.
Le Page F, Kwoh EE, Aurutskaya A et al.
Transcription-coupled base excision repair
and mutation avoidance at 8-oxoguanine
requirement for XPG, TFIIH, and CSB and
implication for Cockayne syndrome. Cell
2000; 101: 159-71.
Itin PH, Sarasin A, Pittelkow MR.
Trichthiodystrophy: update on the sulfurdeficient brittle hair syndromes. J Am Acad
Dermatol 2001; 44: 891-920.
Marshall RR, Arlette CF, Harcourt SA,
Broughton BA. Increased sensitivity of cell
strains from Cockayne's syndrome to sisterchromatid-exchange induction and cell
killing by UV light. Mutat Res 1980; 69:
107-12.
Parris CN, Kraemer KH. Ultraviolet-induced
mutations in Cockayne syndrome cells are
primarily caused by cyclobutane dimmer
photoproducts while repair of other
photoproducts is normal. Proc Natl Acad
Sci USA 1993; 90: 7260-9.
Norris PG, Arlette CF, Cole J et al.
Abnormal erythemal response and elevated
T lymphocyte HRPT mutant frequency in
Cockayne's syndrome. Br J Dermatol 1991;
124: 453-60.
Seguin LR, Tarone RE, Liao KH, Robbins
JH. Ultraviolet light-induced chromosomal
aberrations in cultured cells from Cockayne
syndrome and complementation group C
xeroderma pigmentosum patients: lack of
correlation with cancer susceptibility. Am J
Hum Genet 1988; 42: 468-75.
Price FM, Parshad R, Tarone RE, Sanford
KK.
Radiation-induced
chromatid
aberrations in Cockayne syndrome and
xeroderma pigmentosum group C fibroblasts
in relation to cancer predisposition. Cancer
Genet Cytogenet 1991; 57: 1-10.
Traboulsi EI, De Becker I, Maumenee IH.
Ocular findings in Cockayne syndrome. Am
J Ophthalmol 1992; 114: 579-83.
Higginbottom MC, Griswold WR, Jones KL
et al. The Cockayne syndrome: an
evaluation of hypertension and studies of
renal pathology. Pediatrics 1979; 64: 92934.
Colella S, Nardo T, Mallery D et al.
Alteration in the CSB gene in three Italian
patients with severe form of CS but without
146
clinical photosensitivity. Hum Mol Genet
1999; 8: 935-41.
19. Czeizel AE, Marchalko M. Cockayne
syndrome type III with high intelligence.
Clin Genet 1995; 48: 331-3.
20. Colellia S, Nardo T, Botta E et al. Identical
mutations in CSB gene associated with
either CS or DeSanctis-Cacchione variant of
xeroderma pigmentosum. Hum Mol Genet
2000; 9: 1171-5.
21. Cleaver JE, Volpe JP, Charles WC, Thomas
GH. Prenatal diagnosis of xeroderma
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147
Surgical Pearl
Modifications in punch grafting
Tahir Jamil Ahmad, Tariq Rashid, Zahida Rani
Department of Dermatology, King Edward Medical College/Mayo Hospital, Lahore
Although autologous punch grafting can
be performed on any body area1,2 but it
may cause some appearance problems at
certain sites. Two of such problems are
mentioned with their solution.
1. Hairy areas like eyebrows pose special
problems when they are involved in
vitiligo. Traditional punch grafting of the
area gives satisfactory pigmentation but at
the same time leads to permanent and
disfiguring patchy loss of hair. In such a
situation wedge insertion is suggested
without any loss of hair bearing area.
An incision, 2mm deep is made along the
shaved eyebrow (in the centre, preferably)
and the wound allowed to gape. A wedge
of pigmented skin is incised and placed
with broad epithelial side facing outside
and thin dermal portion going deep in the
recipient area. The tissue is anchored with
stay sutures. Rest of the story of
pigmentation of skin and hair remains the
same.
Figure 1
Punches on hairy areas and
micropockets
Figure 2 Incision line for wedge
2. Thin skin like that on eyelids is also
difficult for grafting3,4 with skin from
relatively thick donor sites. We suggest
micrografting in epidermal pockets at such
places.
Address for Correspondence
Dr. Tahir Jamil Ahmad
186 J, D-H-A, Phase 1, Lahore.
Ph # 042-5726937
148
Figure 3 & 4 Wide bore needles for
micropocketing
Figure 5 Macrografts
Figure 6 Wedge graft positioned with stitches
Figure 8 Complete repigmentation
Donor punches of 1mm in size are taken
and further cut into four pieces under
magnification (since smaller biopsy
punches are not available). Pockets are
made at the dermoepidermal junction with
the help of wide bore syringe needle at
vitiliginous areas with opening at its top.
Micrografts are placed in the pockets and
bandage is applied over it for 48 hours.
The graft take is excellent and
pigmentation areola appears as at any
other site with satisfactory repigmentation.
References
1.
2.
Figure 7 Micropocketing with grafts
3.
4.
Falabella R. Treatment of localized
vitiligo by autologous minigrafting. Arch
Dermatol 1988; 124: 1649-55.
Savant SS. Miniature punch grafting. In:
Savant SS, Atal-Shah R, Gore D, eds.
Textbook and atlas of dermatology
cosmetology, 1st edn. Mumbai: ASCAD;
1998. p. 235-9.
Savant SS. Autologous miniature punch
grafting in stable vitiligo. Ind J Dermatol
Venereol Leprol 1992; 58: 310-4.
Orentreich DS, ed. Punch graft: principles
and techniques of cutaneous surgery, Ist
edn. New York: Mcgraw-Hill; 1996. p.
283-95.
149
Case report
Acrodermatitis enteropathica in three
siblings
Arfan-ul-Bari, *Muhammad Abbas, *Simeen ber Rahman
PAF Hospital, Sargodha.
*Dermatology Department, Military Hospital, Rawalpindi
Abstract Acrodermatitis enteropathica is an autosomal recessive disease due to a partial disorder
of intestinal zinc uptake. Signs usually appear within the first months of life, with a
characteristic cutaneous rash that is symmetrical, located around the body orifices,
behind the ears, and on hands, feet, and head. We report three siblings with
characteristic features of the disease and laboratory evidence of low serum zinc levels.
Symptoms in all three patients reversed remarkably on supplementation of zinc. A
brief history, clinical profile, pathophysiology and treatment of the disease have also
been discussed in this article for better understanding of this disorder.
Introduction
Acrodermatitis enteropathica (AE) was
first described in 1942 by Danbolt and
Closs. The condition is now recognized as
an inborn error of zinc metabolism that is
inherited as an autosomal recessive
disorder.1 Characteristic symptoms in
infancy include periorificial (oral, anal,
genital) and acral dermatitis, diarrhea,
behavioral
and
mental
changes,
neurological disturbances, and secondary
bacterial and fungal infections. In older
children, failure to thrive, anorexia,
alopecia, nail dystrophy, and repeated
infections are more common. Zinc
deficiency may be due to inadequate
intake, malabsorption, excessive loss, or a
combination of these factors. If treated
early, most of the symptoms are reversible
and usually leave no sequelae. The
pathophysiology of AE is not fully
understood.2-4 Untreated patients usually
die within the first few years of life. They
have severe growth retardation, dermatitis,
Address for Correspondence
Squadron Leader Dr. Arfan-ul-Bari
Consultant Dermatologist
PAF Hospital, Sargodha.
Ph# 051-561-33799, 5583688
Email: albariul@yahoo.com
alopecia, secondary bacterial and fungal
infections,
and
neurological
and
5,6
behavioral changes. No race or sex
predilection has been reported. AE
symptoms generally manifest when an
infant is weaned from breastfeeding or
earlier if the infant is formula fed.2-4 Fullterm breastfed infants can develop signs of
zinc deficiency late in the course of
lactation because some nursing mothers
have low levels of zinc in their breast
milk.7-9 AE-like symptoms have been
described in older children and adults who
are on prolonged parenteral nutrition
without
zinc
supplementation.6,10
Erythematous to vesiculobullous or
pustular lesions leading to dry, scaly, or
eczematoid rash distributed around
periorificial and acral areas of the body are
characteristic of AE. The borders of
affected areas are sharply demarcated and
have an accentuation of craquelé like scale
at the periphery. Paronychia may be
present. Partial or total hair loss may be
evident.2-4 Zinc deficiency causes all these
clinical symptoms, which are easily
and rapidly reversible with zinc
150
supplementation and therapy achieves a
survival rate of 100%. In most patients
with AE, plasma zinc concentrations are
low (<50 μg/dl) but this is not diagnostic.
Reference range zinc concentrations have
been reported in patients with AE and low
zinc concentrations may be seen in
patients without AE.11 Plasma level range
is 70–110 μg/dl. Leukocyte zinc level is
very sensitive test for early minor changes,
but is more expensive. Urinary zinc levels
are highly unreliable depending upon body
state of zinc. Normal value is 200–500
μg/24 hrs. Hair and saliva zinc levels are
rarely needed. Production of serum
alkaline phosphatase depends on zinc;
therefore, a low level of alkaline
phosphatase may support an AE
diagnosis.12,13 Skin biopsy reveals nonspecific eczematous changes while
intestinal mucosal biopsies show loss of
villous architecture with increased cell
infiltration in the lamina propria of
patients with AE. These are not routinely
done. Treatment is essentially with dietary
or intravenous supplementation. Dietary
supplementation with 2-3 times the
recommended daily allowance, 3055mg/day of elemental zinc dramatically
reverses the manifestations within hours to
days. Improvement in mental status and
diarrhea is seen within 24 hrs. Severely
infected and erosive lesions show reversal
within 1-2 weeks. A surge of hair growth
may be detected within 3-4 weeks. Zinc
compounds, which appear to be effective,
include zinc complexes with sulfates,
acetates, gluconate, chloride, and amino
acid chelate.2-4,14,15 For most zinc deficient
individuals a single capsule of 220mg zinc
sulfate contains 55 mg of elemental zinc.
In AE, zinc therapy is maintained
throughout the patient's life span, although
periods of remission have been reported.
Exacerbation during pregnancy or the
stress of disease may require an increase in
therapy. In acquired zinc deficiency,
treatment can be stopped after the
precipitating cause has resolved. Zinccontaining foods include oysters, crab,
meat products, human milk, dried beans,
and lentils may also be encouraged. Oral
diodoquine has also got a therapeutic role
probably by enhancing the absorption of
zinc.16
Case histories
Three siblings with respective ages of 11,
8 and 3 years from a low socioeconomic
group family belonging to Tehsil Gujar
Khan, District Rawalpindi presented in
Military Hospital, Rawalpindi with history
of recurrent weeping and crusting lesions
around the mouth and perineum along
with loose motions off and on. The
children were asymptomatic till the age of
about 4 months. They started developing
itchy weeping and crusted lesions over
skin around mouth and perineum during
period of weaning. Later similar lesions
appeared on hands, feet and flexures of
upper and lower limb (Figures 1).
151
Figure 1 Three affected children of a family
showing skin involvement in acrodermatitis
enteropathica
Age (yrs)
11
All the three patients used to have episodic
loose motions which were watery in
consistency, 50–100 ml in volume, 3-4
times a day lasting for 3–7 days. They did
not have jaundice, joint pains, or
abdominal distension. Their parents did
not have any history of blood transfusion,
extramarital sexual contact or intravenous
drug abuse. The three patients were among
the six siblings born to consanguineous
parents (Figure 2). They were all breast
fed till the age of 1–1½ yrs and were
vaccinated to the age. All three had history
of delayed milestones development. On
physical examination all were found to be
fully conscious and well oriented. There
was no pallor, jaundice, cyanosis, clubbing
or lymphadenopathy. Weights and heights
of all the patients were slightly below the
normal lower limit relevant to their age.
8
7
6
4
Figure 2 Pedigree showing whole family. Filled circles and squares show diseased females and
males.
Systemic examination was unremarkable.
Periorificial and perineal areas revealed
eczematous,
lichenified,
and
hyperpigmented lesions. Similar lesions
were also seen in flexures of upper and
lower limbs. Angular cheilitis was present.
Hair were relatively sparse and thin.
Mucous membranes and nails were found
to be normal. Blood profile, urine
152
3
examination, liver function tests, serum
total proteins and albumin were within
normal limit. Serum zinc levels were
36.5μg/dl, 31.4μg/dl and 42.7μg/dl,
respectively. Histopathology revealed
hyperkeratosis,
hypergranulosis
and
epidermal hyperplasia along with upper
dermal perivascular mononuclear infiltrate
(consistent with chronic eczematous
changes). A diagnosis of acrodermatitis
enteropathica was made and patients were
treated with zinc sulfate 2 mg/kg/day. One
week after start of treatment, skin lesions
improved remarkably. On follow up visit
after 1 month diarrhea had settled and
there was a definite improvement in the
general health of the patients.
Discussion
Acrodermatitis is an inherited disorder
transmitted as an autosomal recessive trait
and is caused by inability to absorb
sufficient zinc from diet. In fact the term
acrodermatitis is now being used to
include all the patients with acral
dermatitis due to zinc deficiency,
hereditary or acquired in origin. In order to
understand the disease, a brief overview of
zinc metabolism remains essential. The
adult body contains 2-3 gm of zinc, which
exists almost totally in its oxidized (Zn+2)
form and does not undergo further
oxidation or reduction. Normally about
30% of daily intake is absorbed and 60–
70% of it gets bound to albumin and 10–
20% to α-2 microglobulins.12,13 Because
oral or intravenous zinc supplementation
in patients with AE improves their
symptoms, a defect in zinc metabolism
(especially in intestinal absorption or
bioavailability of zinc in the intestinal
lumen) is a possible pathological pathway.
Grider and Mouat17 described differences
in 2 novel proteins in the fibroblasts
carrying the AE mutation. Wang18 has
recently mapped the AE genetic locus to
band 8q24.3. In infants with AE, an
absence of a binding ligand may
contribute to zinc malabsorption during
weaning. Such a ligand has been identified
in normal pancreatic secretions as well as
in human milk.19 Other causes, such as
high phytate concentrations found in
cereals and soy milk, inhibit zinc
absorption. Geophagia, also decreases zinc
absorption.20 Periorificial and acral
dermatitis can be observed with many
other
conditions,
including
biotin
deficiency, atypical epidermolysis bullosa,
generalized and local candidiasis, atopic
dermatitis, abnormality of essential fatty
acid metabolism, seborrheic dermatitis,
and kwashiorkor. If differentiation
becomes difficult on clinical grounds,
therapeutic trial with zinc can be
distinctive in such cases. Zinc can also
have a role in other diarrhea-like illnesses
and more often zinc deficiency occurs in
association with other micronutrients
deficiencies especially iron and copper and
replacement therapy in such cases has
proved very beneficial.15,21 Reduction in
infant mortality was also noted by zinc
replacement therapy in case of premature
infants.24
Conclusion
Acrodermatitis enteropathica remains one
of the most intriguing disorders known to
medical science. Seldom have so many
physical signs and symptoms, been
attributable to deficiency of one single
element. All of these signs and symptoms
are dramatically reversed by single dietary
supplement of zinc.
References
1.
Danbolt N, Closs K. Arodermatitis
enteropathica. Acta Derm Venereol 1942;
22: 17.
153
2.
Portnoy B, Molokhia M. Acrodermatitis
enteropathica treated by zinc. Br J
Dermatol 1974; 91: 701-3
3. Wells
BT,
Winkelmann
RD.
Acrodermatitis enteropathica: report of six
cases. Arch Dermatol 1961; 84: 40-52.
4. Stevenson JR, Fidone GS, Leland LS.
Acrodermatitis
enteropathica.
Arch
Dermatol 1964; 89: 224-8.
5. Moynahan
EJ.
Acrodermatitis
enteropathica: a lethal inherited human
zinc deficiency disorder (letter). Lancet
1974; 2(7877): 399-400.
6. Sivasubramanian KN, Henkin RI.
Behavioral and dermatologic changes and
low serum zinc and copper concentrations
in two premature infants after parenteral
alimentation. J Pediatr 1978; 93: 847-51.
7. Bilinski DL, Ehrenkranz RA, CooleyJacobs J. Symptomatic zinc deficiency in
a breast-fed, premature infant. Arch
Dermatol 1987; 123: 1221-4.
8. Kuramoto Y, Igarashi Y, Tagami H.
Acquired zinc deficiency in breast-fed
infants. Semin Dermatol 1991; 10: 309-12.
9. Piela Z, Szuber M, Mach B. Zinc
deficiency in exclusively breast-fed
infants. Cutis 1998; 61: 197-200.
10. Arakawa T, Tamura T, Igarashi Y. Zinc
deficiency in two infants during total
parenteral alimentation for diarrhea. Am J
Clin Nutr 1976; 29: 197-204.
11. Garretts M, Molokhia M. Acrodermatitis
enteropathica without hypozincemia. J
Pediatr 1977; 91: 492-4.
12. Gordon EF, Gordon RC, Passal DB. Zinc
metabolism: basic, clinical, and behavioral
aspects. J Pediatr 1981; 99: 341-9.
13. Walravens PA, Hambidge KM, Neldner
KH. Zinc metabolism in acrodermatitis
enteropathica. J Pediatr 1978; 93: 71-3.
14. Leupold D, Poley JR, Meigel WN. Zinc
therapy in acrodermatitis enteropathica.
Helv Paediatr Acta 1976; 31: 109-15.
15. Bhutta ZA. The role of zinc in health and
disease: relevance in child health in
developing countries. J Pak Med Assoc
1997; 47: 68-73.
16. Dallaha CJ, Lorincz AL, Aarnik ON.
Acrodermatitis enteropathica: review of
the literature and report on a case
successfully treated with diodoquin.
JAMA 1953; 152: 509-12.
17. Grider A, Mouat MF. The acrodermatitis
enteropathica mutation affects protein
expression in human fibroblasts: analysis
by two-dimensional gel electrophoresis. J
Nutr 1998; 128: 1311-4.
18. Pugh EW, Griffen S. Homozygosity
mapping places the acrodermatitis
enteropathica gene on chromosomal
region 8q24.3. Am J Hum Genet 2001; 68:
1055-60.
19. Lonnerdal B, Stanislowski AG, Hurley
LS. Isolation of a low molecular weight
zinc binding ligand from human milk. J
Inorg Biochem 1980; 12: 71-8.
20. Prasad AS. Zinc: an overview. Nutrition
1995; 11 (Suppl 1): 93-9.
21. Bhutta ZA, Nizami SQ, Isani Z. Zinc
supplementation in malnourished children
with persistent diarrhea in Pakistan.
Paediatrics 1999; 103: 42.
154
Case report
A family with xeroderma pigmentosumCockayne syndrome complex.
Ijaz Aman, *Shahbaz Aman, Tahir Massod Ahmad
Department of Paediatric Medicine, King Edward Medical College/Mayo Hospital, Lahore.
*Department of Dermatology, King Edward Medical College/Mayo Hospital, Lahore.
Abstract Xeroderma pigmentosum-Cockayne syndrome complex is the coexistence of two
genodermatoses, xeroderma pigmentosum (XP) and Cockayne syndrome (CS) in one
patient. The patients of this syndrome present with photosensitivity, freckling on sunexposed skin, loss of subcutaneous fat from face, prominent ears, dwarfism,
microcephaly, mental retardation or other neurological and eye abnormalities. Many
similar cases with additional features have been reported in foreign literature. We
describe 3 cases of this syndrome along with review of literature.
Introduction
Xeroderma
pigmentosum-Cockayne
syndrome
complex
is
one
of
the
genodermatoses
including
photosensitivity, freckling, ocular defects,
disproportionately large hands, feet and
ears, microcephaly, mental retardation and
other
neurological
abnormalities.1,2
Photosensitivity
with
neurological
abnormalities of variable severity can
occur in various genodermatoses like
xeroderma pigmentosum (XP) and its
variants, Cockayne syndrome (CS),
trichothiodystrophy and Hartnup disease.13
Other differential diagnoses include
Bloom’s syndrome and progeria.1,2,3 In
many of these the underlying molecular
defects have been demonstrated. These
include nucleotide excision repair defects,
reduced unscheduled DNA synthesis and
increased chromatid exchange.2-4 The
diagnosis of this group of diseases in our
part of the work is based on clinical
features due to lack of facilities for genetic
studies. We describe, for the first time, 3
Address for Correspondence
Dr. Ijaz Aman
2-C, Hearn Road, Islampura
Lahore.
Ph#042-7226054
cases who have both the features of
xeroderma pigmentosum and Cockayne
syndrome.
Case report
Three brothers of ages 12, 7 and 2 years
presented at the out-patient department of
Paediatric Medicine, Mayo Hospital,
Lahore in September 2001 with a history
of photosensitivity and black-brown
pigmented spots on face and other exposed
parts with redness and soreness of eyes.
The children were born to a
consanguineous couple after an uneventful
pregnancy and labour. They were normal
at birth and the symptoms began at ages 9,
12 and 17 months, respectively. They
developed black-brown pigmented spots
and scaly lesions over their faces and back
of hands after sun exposure. Their
complexion gradually became dark and
skin became dry. Two of them also had
excessive lacrimation and redness of eyes.
The symptoms used to exacerbate
particularly during hot weather and febrile
illnesses. They also developed anorexia,
weight loss and thinning out of nose
155
weight loss and thinning out of nose.
Figure 1 Dry scaly, freckling, atrophy
involving face in a butterfly distribution,
prominent ears and premature senile
appearance.
Figure 2 Long lower extremities with genu
valgum.
However, there was no complaint of
seizures or hearing deficit in our patients.
They remained underweight as compared
to their peers. They attained normal motor
milestones but cognitive functions were
impaired and the eldest child was the
student of class one. They had
progressively increasing difficulty in
walking with tremulous movements of
hands especially when performing any
task. Another sibling with similar skin
lesion had died at the age of 11 months
due to unknown reasons while other
family members did not suffer from
similar illness.
Physical examination revealed three thin
built, anxious looking boys with short
stature. They had dry, scaly skin and
freckling involving face in a butterfly
distribution (Figure 1). They had pinched
nose, atrophy of the facial skin, loss of
subcutaneous fat and prematurely senile
appearance.
There
were
no
vesiculobullous,
eczematous
or
telangiectatic lesions seen in our patients.
Similarly, there were no cutaneous lesions
suggestive of malignant transformation.
Heights of all three children were less than
5th percentile. Hands and feet were
relatively large. Lower limbs were
disproportionately long as compared to the
trunk in the eldest child (Figure 2) while
younger children were normal. Ears were
relatively large while hair, nails and
mucous membranes were normal. They
also had carious teeth and skeletal
abnormalities which included restriction of
knee joint movements with lumbar
lordosis and genu valgum (Figure 2).
Neurological examination revealed broadbased gait and spasticity, pointing a defect
in cerebellum. Other cerebellar signs
included intention tremors, past pointing
and incoordination. Deep tendon reflexes
in the lower limbs were exaggerated with
up going plantars. However, there was no
nystagmus, choreoathetosis or ataxia in
our patients. Photophobia was found in all
156
the three patients while keratitis was noted
in one patient. Hearing was found to be
normal. Psychiatric analysis showed lower
IQ in all the three patients. Their mental
age was assessed to be 6, 4 and 1 year,
respectively on portage guide.
Laboratory investigations showed no
abnormality. EEG was also normal while
CT scan of brain in eldest child showed
foci of calcification at basal ganglia.
Nucleotide excision repair, unscheduled
DNA synthesis and complementation
assay studies could not be performed due
to unavailability.
Discussion
Cockayne syndrome, first described by a
British pediatrician in 1936, is a rare
autosomal recessive degenerative disease
with cutaneous, ocular and neurological
abnormalities.3 The syndrome has classical
and non-classical types.4 One of the nonclassical variety has features of both XP
and CS and a number of cases have been
reported.4,5 The disease usually starts
during the second year of life with slowly
progressive neurological degeneration,
intellectual
impairment,
deafness,
peripheral neuropathy, normal pressure
hydrocephalus and microcephaly.1
The cutaneous findings seen in our
patients included photosensitivity with
pigmentary abnormalities as seen in XP.1
A thin nose, large hands and feet with
larger lower limbs as compared to trunk
are conspicuous of CS.1-4 Ocular
abnormalities included photophobia in all
cases and keratitis in one child, the
findings being present in both syndromes
while the characteristic ‘salt and pepper’
appearance of retina, cataract and optic
atrophy present in CS were not seen in our
cases.4-6 We did not find any lesion
suggestive of malignant change in our
cases similar to CS in which there is no
increase in the incidence of neoplasia.1,3
Hypereflexia in lower limbs of our cases is
a useful diagnostic feature of CS rather
than XP.2,5 Although our patients were
mentally
retarded
and
had
photosensitivity, there were no hair and
nail changes, ichthyosis or pellagra-like
skin manifestations. Hence the diagnosis
of trichothiodystrophy and Hartnup
disease were not considered. Dwarfism
and premature senile appearance are also
features of progeria but photosensitivity,
disproportionately
large
extremities,
normal hair and demyelination are not
present in cases of progeria. In Bloom’s
syndrome, the erythema of face and hands
is associated with growth retardation, but
mental development is normal.
Poor cognition, spasticity, incoordination
and upper motor neuron signs in the lower
limbs indicate central and peripheral
demyelination, the signs of CS.5-6
Confirmation of the diagnosis by assay of
DNA repair in skin fibroblasts, protein
complementation studies and molecular
genetic testing of the two genes (ERCC6,
ERCC8) could not be done due to lack of
facility. The final diagnosis of XP-CS
complex could only be made on clinical
background. They were prescribed topical
sun screen lotions with advice to avoid
sunlight. Currently, the patients are under
observation with continued treatment.
References
1.
2.
Harper JI. Genetics and genodermatoses.
In: Champion RH, Burton JL, Burns DA,
Breathnach SM, eds. Textbook of
dermatology, 6th edn. Oxford: Blackwell
Science; 1998. p. 357-436.
Kraemer KH. Heritable diseases with
increased sensitivity to cellular injury. In:
Freedberg IM, Eisen AZ, Wolff K et al.,
eds. Dermatology in general medicine, 5th
157
3.
4.
5.
edn. New York: McGraw-Hill; 1999. p.
1848-62.
Levy M, Hirschhorn K, Willner J.
Disorders with photosensitivity. In: Pine
JW, Mullen ML, eds. Genodermatoses: a
full color clinical guide to genetic skin
disorders, 6th edn. New York: JB
Lippincott; 1996. p. 204-12.
Nance MA. Cockayne syndrome. Gene
Reviews,
2001;
1-13.
http://www.geneclinics.org/servlet/access.
Mallory S. Disorders with malignant
potential. In: Pine JW, Mullen ML, eds.
Genodermatoses: a full color clinical
guide to genetic skin disorders, 6th edn.Le
6.
7.
New York: JB Lippincott; 1996. p. 15068.
Butterworth T, Ladda RL, eds. Clinical
genodermatology. New York: Praeger
Scientific; 1981.
Kraemer KH, Scotto J. Xeroderma
pigmentosum: cutaneous, ocular and
neurologic abnormalities in 830 published
cases. Arch Dermatol 1987; 123: 241-50.
158
Quiz
An erythematous plaque on the breast
Faria Asad, Sabrina Suhail Pal
Department of Dermatology, King Edward Medical College/Mayo Hospital, Lahore
Report of a case
A 46-year-old woman presented with
erythema and scaling of the nipple and
areola of her right breast for the last one
and a half years. It was associated with
itching, mild burning and serous
discharge.
She
applied
various
medicaments over the past years but there
was only symptomatic relief.
Physical examination revealed an illdefined, crusted, erythematous plaque
involving the nipple and areola of right
breast associated with mild retraction of
the nipple. Breast examination did not
reveal any palpable mass. Axillary lymph
nodes were not enlarged. Her systemic
examination and laboratory investigations
were unremarkable. A biopsy was taken
for histopathology (Figure 1 and 2).
Figure 1 (Haematoxylin-eosin, original
magnification x 40)
What is your diagnosis?
Figure 2 (Haematoxylin-eosin, original
magnification x 400)
Address for Correspondence
Dr. Faria Asad,
Department of Dermatology,
Mayo Hospital, Lahore.
159
Diagnosis
Paget’s disease of breast
Microscopic findings and clinical course
Section of the biopsy specimen showed
infiltration of the acanthotic epidermis
with numerous Paget cells lying singly and
in groups. These were large, rounded cells
that contained a large nucleus and ample
cytoplasm. The cytoplasm of these cells
stained much lighter than that of adjacent
squamous cells which were compressed
between them. There was no invasion of
the dermis by Paget cells. Chronic
inflammatory cells were present in the
upper dermis.
Discussion
Paget’s disease of breast occurs almost
exclusively in women, but a few instances
of its occurrence in male breast have been
described.1 It is a rare disorder of nippleareola complex that is often associated
with an underlying in situ or invasive
carcinoma.2 It is characterized by
progressive, eczematoid changes with
persistent soreness or itching. Due to its
seemingly benign appearance, diagnosis is
often delayed. There are two main theories
regarding the histogenesis of the disease:
the epidermotropic and the in situ
transformation. The first suggests that
Paget cells are ductal cells that have
migrated from an underlying carcinoma of
breast parenchyma to the epidermis of the
nipple. The second postulates that nipple
keratinocytes undergo transformation into
malignant cells independent from any
pathology within the breast parenchyma.3
In 50% of the cases, a palpable mass is
evident and it usually represents an
infiltrating carcinoma with involved
axillary lymph nodes. In the absence of a
mass, the prognosis is invariably better as
it reflects a non-invasive tumor. The
standard treatment is mastectomy.
Although in our patient, no palpable mass
or lymphadenopathy was present, yet a
biopsy was imperative. For long-standing
unilateral breast eczema which is not
responsive to medicaments a skin biopsy
to confirm or rule out Paget’s disease.
References
1.
2.
3.
Satiani B, Powell RW, Mathews WH.
Paget’s disease of male breast. Arch Surg
1977; 12: 587-92.
Sakorafas GH, Blanchard DK, Sarr MG.
Paget’s disease of the breast: a clinical
perspective. Langenbecks Arch Sur 2001;
386: 444-50.
Lev-Schelouch D, Sperba F, Gat A.
Paget’s disease of the breast. Harefuah
2003; 142: 433-7.
160
News
2004
National events
2003
September 26-28, 2003
10th Annual Conference of Dermatology
- Bhurban, Pakistan.
For further information contact:
Dr. Riaz A. Sheikh, 10-F, PIMS Campus,
G/8-3, Islamabad - 4400 Pakistan.
Tel: +92 51 9261203, 0300 9505421
E-mail: derma_2003@yahoo.com, or
riaz_a_sheikh@yahoo.com
2004
December 9-12, 2004
Silver Jubilee Conference of Pakistan
Association of Dermatologists, Karachi.
Organizing Chairman: Dr. Khurshid H.
Alvi, K.V. SITE Hospital, Karachi.
Tel: +92 21 7789666
Fax: +92 21 7789677
E-mail: info@pad.org.pk,
badr@pad.org.pk
May 19-22
IX ISD International Congress on
Dermatology, Beijing, China
Contact: International Congress Secretariat
Tel: +86 10 6524 9989 ext 1606
Fax: + 86 10 6512 3754
E-mail: icd2004@chinamed.com.cn
November 17-21
13th Congress of the European Academy
of Dermatology and Venereology
Contact: Torello M. Lotti, Florence, Italy
E-mail: president@eadv2004.org or
info@eadv2004.org
February 6-11
American Academy of Dermatology 62nd
Annual Meeting, Washington, DC
For more information contact:
American Academy of Dermatology, 930
E Woodfield Rd, Schaumberg, IL
60173/847-330-0230; fax 847-330-1090.
E-mail: rescalante@aad.org
2005
International events
2003
October 15-18
12th Congress of the European Academy
of Dermatology and Venereology
Mario Lecha, Barcelona, Spain
E-mail: congresos@atlantaviayes.es
www.eadv.org
October 12-15
European Academy of Dermatology and
Venereology Congress (EADV)
London, UK
Contact: Marilyn Benham
Tel: 020 7383 0266
E-mail: eadv@bad.org.uk
www.eadv.org
November 9-12
14th Congress of Aesthetic Medicine
Las Vegas, Nevada, USA
Tel: 604 681-5226
Fax: 604 681-2503
E-mail: congresos@venuewest.com
www.venuewest.com/aestheicmedicine2003
161
Information for Authors
Manuscripts
The JPAD agrees to accept manuscripts prepared in
accordance with the “Uniform Requirements for
Manuscript Submission to the Biomedical Journals”
approved by the International Committee of
Medical Journals Editors. Three copies of all
material for publication should be sent to Dr. Ijaz
Hussain,
Editor,
JPAD,
Department
of
Dermatology, Mayo Hospital, Lahore, e-mail:
dderma@paknet4.ptc.pk
dr_ijazhussain@yahoo.com
Manuscripts should be printed on one side of paper
only, with a 2.5 cm margin on either side, be
double spaced, and bear the title of the paper, name
and address of each author, together with the name
of the hospital, laboratory or institution where the
work has been carried out. The name and full
address of corresponding author should be given on
the first page. Pages should be numbered. Authors
should keep a copy of the manuscript.
In addition to the hard copy, an exact copy of the
manuscript, containing all parts of the paper, must
be submitted on high-density disk. The editor
reserves the right to make corrections, both literary
and technical, to the papers. Papers received are
supposed to have been submitted exclusively to the
Journal of Pakistan Association of Dermatologists
and all authors must give a signed consent to
publication in a letter sent with the manuscript.
Authorship implies a significant contribution. In
case of clinical trials, the names of pharmaceutical
sponsors should be mentioned.
Types of articles
JPAD welcomes original and review articles, case
reports, quizzes, items of correspondence etc.
addressing any aspect of dermatology.
The original article should be of about 2000 words,
with no more than 6 tables or illustrations. Letters
should not normally exceed 400 words and have
more than 10 references.
Parts of the paper
The manuscript should be prepared as below.
Title: In addition to the full title of the paper, a short
version not more than 50 characters, for a running
head, be provided.
Author(s) details: Name(s) of the author(s) should
be given as initial(s) followed by surnames, and
should be clearly linked to the respective addresses
by the use of symbols e.g. , †,‡ etc.
Abstract: All articles other than correspondence
should have an abstract. The original articles should
have a structured abstract comprising of 4
subheadings: background, methods, results and
conclusions. Keywords  5 should be provided to
aid indexing.
Main text: The main text should appear in the
following sequence: introduction, methods, results,
discussion, acknowledgments, references, tables and
legends for illustrations. Each section should begin
on a new page. Generic names of the drugs should
be used. Full names with abbreviations must be
used given with the first mention, thereafter the
abbreviation will be used. Abbreviations should be
used for unwieldy names or where the names occur
frequently. For all quantitative measurements the
International System of Units (SI) should be used.
References
Only papers closely relevant to the author’s work
should be referred to. References should be in the
Vancouver style i.e. references should be written as
unbracketed superscript numbers in the order in
which they appear in the text e.g. ‘our previous
reports1 and that of Cohen et al.2…..’. At the end of
the article, references should give the name(s) and
initials of author(s). If there are more than four
authors, include the first three authors followed by
et al., title of paper, title of the journal abbreviated
in the standard manner (as published in the Index
Medicus), year of publication, volume number, and
first and final numbers of the article, e.g. Grattan C,
Powell S, Humphreys F. Management and
diagnostic guidelines for urticaria and angiooedema. Br J Dermatol 2001; 144: 708-14.
References to books should give the name(s)
followed by initials of author(s) or editor(s), chapter
(if relevant), book title, edition, place, publisher,
year, and pages referred to e.g. Friedman WF, Child
JS. Congenital heart disease in the adult. In: Fauci
AS, Braunwald E, Isselbacher KJ et al., editors.
Harrison’s principles of internal medicine. 14th edn.
New York: McGraw-Hill; 1998. p. 1300-9.
Tables
There should be as few tables as possible and these
should include only essential data. These should be
printed on separate sheets and should be given
Arabic numbers. No horizontal or vertical rules
should be used. Avoid wordy, over-full tables.
Legends should be provided.
Illustrations
Three sets of illustrations should be sent with each
manuscript. Illustrations should be referred to in the
text as ‘Figures’ and be given Arabic numbers.
Each figure should be marked on the back with the
name of the author(s), the title of the paper and the
reference number used in the text. Orientation of the
illustration should be indicated by marking the top
with arrow. Photographs should be unmarked glossy
prints. Diagrams should be on separate sheets and a
legend should be provided for each illustration.
Proofs
Page proofs will be sent, without the original
manuscript, to the corresponding author for proof
correction and should be returned to the editor
within three days. Major alterations from the text
cannot be accepted. Any alterations should be
marked, preferably in red.
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