PRESENTATION OF BEHCET”S DISEASE AMONG NIGERIANS
Word count: Abstract 232, body 1652
1.
Table count:
6
Figure count:
5
Dr F.O.A Ajose,
Dermatology Unit, Lagos State University Teaching Hospital, Ikeja. Lagos
2.
Prof O.O. Adelowo,
Rheumatology Unit, Lagos State University Teaching Hospital, Ikeja. Lagos
3.
Dr O. Oderinlo
Eye Foundation Hospital, Ikeja. Lagos
Correspondence:
Dr Frances O. A. Ajose FRCP(Lond)
PO Box 1723. Surulere, Lagos. Nigeria
Email- francesajose@yahoo.co.uk
Funding: self
Conflict of Interest: Nil
1
ABSTRACT
Background: Behcet’s Disease (BD) is a chronic multisystemic inflammatory pan-vasculitis of
unknown aetiology, which commonly involves the skin, joints, eyes, mucosa, central nervous
system and gastrointestinal tract.
It is considered to be due to an auto immune reaction triggered by a yet to be identified infectious
agent in a genetically predisposed person. It most commonly affects persons of Mediterranean
and Far Eastern origin and is considered to be rare among black Africans.
Objective: To document the clinical pattern of Nigerian patients presenting with Behcet’s
disease at a tertiary hospital in Nigeria.
Method: A retrospective study of patients who attended dermatology and rheumatology clinics
of Lagos State University Teaching Hospital, Ikeja, Nigeria between August 2007 and August
2011 and who fulfilled the ISG diagnostic criteria for Behcet's Disease. Patients were referred
from hospital specialists that included ophthalmologists, dentists, psychiatrists and
otorhinolaryngologists.
Result: Fifteen patients, (female 11, male 4) aged between 22-50years, were diagnosed with
BD. Onset was mostly in the second decade but diagnosis was made at a mean age of
33years.Mucosal BD was predominant at80%,with mixed mucosal and ocular pattern in 60%,
and mixed mucosal and neuro Behcet's in 13%. Articular involvement was present in 87%.
Management was with standard immunosuppressive agents.
Conclusion: BD though rare, is seen among Nigerians and its presentation is not much different
from reports elsewhere.
2
Key words: Behcet's Disease, Uveitis, Arthritis, Genital ulcers, Erythema Nodosum, Nigerians
3
INTRODUCTION
Behcet’s disease (BD) also often called Behcet’s syndrome, because of the uncertainty of its
pathogenesis and lack of diagnostic tests, is a chronic auto inflammatory disorder of unknown
aetiology. It is considered to be an auto immune condition triggered by a yet to be identified
infectious agent in a genetically predisposed person and under certain environment.1,2 The
disease has been reported worldwide, though it is mostly seen in persons along the old ‘silk
route’ of eastern Mediterranean, Middle East and East Asia. The condition is also more severe in
these areas.3 Turkey probably has the highest occurrence of the disease with a prevalence of
between 110 - 420 per 100, 000 population, 2, 3 while in Japan it is seen in 13–20 per 100,000
population.
It has been infrequently reported in Northern Europe, Africa and the Americas.4 All ages are
affected. Frequency is, however, higher in persons in their third or fourth decade of life, with a
mean of 25 – 30 years. Sex predominance is also variable in different geographical areas. Thus,
while the female to male frequency is identical in patients along the ‘silk route’, there is a female
preponderance in Japan, Korea and the western countries.3, 4
The clinical manifestations are protean and these have been attributed to an underlying vasculitis
that may involve an artery or vein in any organ.5 Behcet’s disease however mostly affects the
skin, eyes, mucous membranes and the central nervous system. Other systems such as the
musculo-skeletal, gastro-intestinal and genito-urinary may however also be involved.
There have been few reports from Africa and these are among North African Tunisians and
Egyptians.6, 7 but very few cases have been reported among Sub-Saharan Africans.8, 9 There are,
4
however, case reports among black Africans resident in United Kingdom.10 There have been no
documented reports of BD among Nigerians and other West Africans.
The objective of this study therefore is to document the clinical presentation of Behcet’s disease
among Nigerians and compare their presentations with reports elsewhere.
PATIENTS AND METHODS
This is a retrospective study of patients with BD who presented to the dermatology and
rheumatology clinics of Lagos State University Teaching Hospital, Ikeja between 2007and
2011.The hospital is located in Lagos, the commercial capital and most populous state in Nigeria
and receives patients from all over the country. The study patients fulfilled the criteria of the
International Study Group (ISG) on Behcet’s Disease which included recurrent oral ulcers,
recurrent genital ulcers, eye lesions, skin lesions and pathergy.11 Table 1 shows sources of
referral of the BD patients. All patients had complete blood count, erythrocyte sedimentation
rate, and in some patients serology that included antinuclear antibody, rheumatoid factor, HIV
and syphilis diagnostic tests. Treatment was essentially with the standard drugs used in BD,
including corticosteroids and Disease Modifying Anti- rheumatic Drugs.
RESULTS
A total of 15 Nigerians fulfilled the ISG criteria for Behcet’s Disease over the four year study
period. All but four of the patients presented as undiagnosed referrals from various departments
in the hospital (Table 1). The demographic characteristics of the patients are as in Table 2.
Females were predominant. The mean age at presentation was 33.3 years (range 22-40). The
commonest presentation was mouth ulcers (Table 3) with the tongue being the commonest site.
Fig 1 shows ulcer on the tongue of one of the patients. Episodes of painful ulceration were
5
without fevers or regional lymphadenopathy. The scrotum in males (Fig 2) and labia in females
were the commonest sites of genital ulceration. Dyspareunia was significant complaint in two
females and in one of the male patients, scrotal ulceration was severe enough to mimic
Fournier’s gangrene. Tests for HIV, syphilis and chlamydia were negative in all the 11patients so
tested.
Erythema nodosum was the commonest skin involvement, being seen in 9 cases. Other skin
involvement included pseudo-folliculitis (Fig.3), pustules at injection sites, superficial
thrombophlebitis and hair structure changes. Table 3 highlights the frequency of the skin
changes.
Eye involvement was seen in 12 out of our 15 patients. The ocular involvement was preceded by
oral and genital ulcers in all the cases. Eye involvement was bilateral in all cases with anterior
uveitis in 5 patients (Table 3) and transient hairline hypopyon in one patient. Posterior uveitis
was seen in 4 patients and pan- uveitis with severe retinal damage in 2 cases (Fig 4&5). Ultra
sound scanning of the retina in one of these patients (Figs 6 & 7) shows extensive vitritis and
posterior vitreous detachment.
Arthritis was present in 87% (13/15) with a total of 19 joints involvement (Table 3). The knee
was the commonest joint involved and most patients had more than one joint involvement.
Anxiety and depression were the commonest manifestation of Central Nervous System (CNS)
involvement (Table5), present in 9 out of 15 patients. Other CNS involvement included
sensorineural deafness in 3 patients. One patient had transient facial nerve palsy, hemiparesis and
seizures and another patient presented with psychomotor hyperactivity and cognitive
impairment.
6
Laboratory results were as in Table 6 with most of the patients having elevated erythrocyte
sedimentation rate. Serology for ANA, syphilis were negative in all tested. Treatment was
mostly with corticosteroids and immunosuppressives. Twelve patients received corticosteroids
with or without immunosuppressives. Three patients had methotrexate or azathioprine, in
addition to corticosteroids. Two patients received colchicine and another, cyclosporine, for
variable periods.
DISCUSSION
Although worldwide in distribution, Behcet’s disease has rarely been reported among SubSaharan Africans. Probably the largest documented case series was by Jacyk8 who reported 5
cases from South Africa. Nunzi et al9 reported a case from Congo. Another report from
Comoros12 involved 14 cases. In a report of Behcet’s disease patients of West African and AfroCaribbean origin living in London, United Kingdom, Poon et al10 confirmed the rarity of this
disease. He suggested environmental factors, absent in the patients’ home country, as
contributing to the disease presumably because no previous report of BD had come from West
Africa. The eight patients in the report of Poon et al had lived in the United Kingdom for a
number of years. Although, all the six patients tested were negative for HLA B 51, they
nevertheless concluded that their clinical progress was similar to European patients. This view
was supported by the finding of refractory ocular inflammation that responded poorly to
immunosuppressives.
The mean age of onset in our patients was 27.3 while mean age at presentation was 33 years in
consonance with the commonly reported age range of 25 – 30 years elsewhere.13 There was
therefore an average delay of six years before appropriate diagnosis was made. While females
7
and males are reported in equal proportions in most studies, our cohort had a marked female
preponderance of 11 to 4. In sharp contrast to the male preponderance in the study from the
Comoros (F-4: M-10). The reason for this female preponderance is unclear as it cannot be
explained by the slight female preponderance in our hospital patient attendance.
As in the other studies, oral and genital ulcers were the commonest presentation in our cohort.
Twelve (80%) had eye involvement unlike the 50% reported by Evereklioglu.14 Although
transient hypopyon is often thought to be the hallmark of ocular presentation in BD5 and TugalTutkum et al. reported this in 12% of their series,15 only one of our patients had hypopyon.
Furthermore, anterior / posterior uveitis rather than pan uveitis was predominant among our
patients.
Arabaci et al
16
and Direskeneli17 found poor dental hygiene in their cohort, but our patients’
hygiene indices were fair to good. This difference may be due to the fact that most of our
patients used local chewing stick which is better tolerated than the standard toothbrush in periods
of oral ulceration.
The commonest skin manifestation among our patients was erythema nodosum which was seen
in nine out of our 15 cases (60%). Erythema nodosum has previously been reported in 50% of
patients with BD.18 The change in hair structure to a silky texture was observed in two patients.
This strange regression of African hair to the neonatal hair structure had been reported in other
chronic diseases including HIV and Rheumatoid arthritis.19
Arthritis was seen in 80% of our patients who had a total of 19 joint involvements. As reported
elsewhere, oligo - articular presentation was most frequent and the knee and ankle, the
commonest sites.
8
CNS involvement was present in 12 patients in our study. Unlike the findings of Borhani et al20
depression rather than somatisation was the significant psycho morbidity, although we used a
different instrument. However we did not find symptoms attributable to somatization in our
patients. Hemiparesis and transient facial nerve palsy were observed in one patient each.
Cerebrospinal fluid examination and imaging studies were however not done.
Treatment was mostly with corticosteroids and/or immunosuppressives and choice was
dependent on availability of these medications.
The limitation of this study was that HLA B51 which characterizes Behcet’s Disease was not
available to us. However studies of the global distribution of HLAB51 had indicated its rarity
among Sub Saharan Africans.9
This was supported by the study from the Comoros13 which
reported this allele negative among east African BD patients. Nevertheless it would be useful to
know that this is so in our population. Another limitation was default rate among the patients
which made assessment of the efficacy of the drugs used difficult. The rather long onset to
diagnosis period of six years may indicate a poor ascertainment of the disease among relevant
clinicians in Nigeria which should be addressed. With improved ascertainment, it is hoped that
more cases will be diagnosed and a larger prospective study may then elucidate this condition
further
CONCLUSION
Behcet’s disease is here reported for the first time among 15 Nigerians. Whilst the number is
small, the presentation may reflect the rarity of BD in the Nigerian population or poor
ascertainment of the disease among relevant clinicians. It is hoped that this study will increase
9
the awareness of this condition among clinicians attending to African patients in Africa and
elsewhere.
REFERENCES
1.
Onder M, Gurer MA. The multiple faces of Behçet’s disease and its aetiological factors. J Eur
Acad Dermatol Venereol 2001; 15:126–36.
2.
Direskeneli H. Behcet’s disease: Infectious etiology, new auto antigens, and HLA-B51 Ann.
Rheum Dis. 2001: 60: 996-1002
3.
Zouboulis C. C. Epidemiology of Adamantiades – Behcet’s disease. In: Zierhut M, Ohno S, eds.
Immunology of Behcet’s Disease. Amsterdam: Grafischm Produktiebedrijf Gorter 2003: 1-16
4.
Zouboulis C C, Kotler I, Diawarr D, et al. Adamantiades – Behcet’s disease: epidemiology in
Germany and in Europe. In: Lee S, Bang D, Lee ES, Lee S, Eds. In Behcet’s disease A guide to its
clinical understanding. Textbook and Atlas. Springer 2001; 157 – 69
5.
Schirmer M, Calamia K T. Is there a place for large vessel disease in the diagnostic criteria for
Behcet’s disease? J Rheumatol. 1999; 26: 2511-2
6.
Houman MH, Neffati H, Braham A et al Behcet’s disease in Tunisia. Demographic, clinical and
genetic aspects in 260 patients. Clin. Exp. Rheumatol 2007. Jul-Aug; 25 (4 suppl 45):558-64
7.
El Menyawi MM, Raslan HM, Edrees A. Clinical features of Behcet’s disease in Egypt Rheumatol
Int 2009 Apr; 29 (6): 641-6
8.
Jacyk WK. Behcet’s disease in South African Blacks: report of five cases
J Am Acad Dermatol 1994 May; 30(5 Pt 2): 869 -73
9.
Nunzi E, Clapasson A, Di Negro G, Noto S. A case of ‘silk route disease’ in a patient from Congo.
G G.Ital..Dermatol Venereol 2008 Jun; 143(3): 225-6
10. Poon W, Verity DH, Larkin GL, Graham EM, Stanford MR. Behcet’s disease in patients of west
African and Afro-Caribbean origin. Br J Ophthalmol 2003;87:876-878
10
11. International Study Group for Behcet’s Disease: Criteria for diagnosis of Behcet’s disease.
International study Group for Behcet’s Disease. Lancet 1990;335:1078-80
12. Liozon E, Roussin C, Puechal X et al. Behcet’s disease in East African Patients may not be
unusual and is an HLA B51 negative condition: A case series from Mayotte (Comoros). Joint Bone
Spine 2010 July 2 [Epub ahead of print]
13. H. Yazici, Y. Tuzun, H. Pazarli, S. Yurdakul et al. Influence of age of onset and patient's sex on
the prevalence and severity of manifestations of Behcet's syndrome. Ann. Rheum Dis, 1984, 43,
783-789
14. Evereklioglu C. Current concepts in the etiology and treatment of Behcet’s disease. Surv.
Ophthalmol 2005;50(4): 297-350
15. Tutkum I, Onal S, Altan-Yaycioglu R et al Uveitis in Behcet’s disease: an analysis of 880 patients.
Am J Ophthalmol 2004;138(3): 373-380
16. Arabaci T, Kara C, CiçekY. Relationship between periodontal parameters and Behcet's
disease and evaluation of different treatments for oral recurrent aphthous stomatitis.
J
Periodontal Res. 2009 Dec;44(6):718-25. Epub 2008 Dec 11.
17. Direskeneli H, Mumcu G. A possible decline in the incidence and severity of Behcet's
disease: implications for an infectious etiology and oral health. Clin Exp Rheumatol. 2010
Jul-Aug;28(4 Suppl 60):S86-90. Epub 2010 Sep 24.
18. Yazici H, Fresco I, Stuebiger N. Behcet’s syndrome, relapsing polychondritis, and eye
involvement in rheumatic disease In: Bijlsmaed Eular Compendium on Rheumatic Diseases BMJ
Publishing Group 2009:357-374
19. Ajose, F. O. A. (2012), Diseases that turn African hair silky. International Journal of Dermatology,
51: 12–16. doi: 10.1111/j.1365-4632.2012.05556.x
20. A. Borhani Haghighi, E. Aflaki1, H. Haghshenas2, et al. Psychometric evaluation of patients with
Behçet's disease Iran J. Med Sc. June 2007; Vol 32 No 2
11
Ophthalmology
4
Self- referral
4
Otorhinolaryngology 2
Gynecology
2
Urology
2
Psychiatry
1
Table 1.Sources of referrals of Behcet's Disease patients in Nigeria
12
Total number of 15
Subjects
-
Female (%)
11(73.3)
-
Male (%)
4(26.7)
Age range
16-40
Mean
32.9
Table 2: Demography of Behcet's Disease patients in Nigeria
13
1.
Mouth ulcers
15
2.
Genital ulcers
Scrotal
Vulva
Perineal
Arthritis
Ankle
Knee
Wrist
Elbow
Skin Involvement
Erythema nodosum
Pseudofolliculitis
Thrombophlebitis
Pustules at injection
sites
Hair Structure changes
14
3
9
2
12
8
9
1
1
12
9
7
3
3.
4.
5.
5
2
Eye Involvement
9
Anterior Uveitis
5
Posterior Uveitis
4
Pan Uveitis
2
Transient
hairline 1
hypopyon.
Table 3: Clinical presentations in Behcet's Disease patients in Nigeria
14
Depression
9
Anxiety
4
Cognitive symptoms
1
Sensorineural deafness
1
Hallucinations, Delusions
1
Hemiparesis
1
Facial Nerve Palsy
1
Chorea
1
1
Seizures
Table 4: Neuro-psychiatric presentations of Behcet's Disease patients in Nigeria
15
Haematocrit:
Range
29-45 %
Mean
36 %
ESR:
Range
21-150mm/hr
Mean
72.8mm/hr
Serology:
ANA
8 negative (7 not done)
Retrovirus
12 negative (5 not done)
Syphilis
11 done (all negative)
Table 5: Laboratory Investigations of Behcet's Disease patients in Nigeria
16
Corticosteroids,
Prednisolone/
Pulse 12
Methylprednisolone
Azathioprine
3
Methotrexate
3
Cyclosporin
1
Colchicine
2
Table 6: Treatment of subjects withBehcet's Disease in Nigeria
17
Fig 1. Ulcers on the tongue of 34 year old male Nigerian with Behcet’s Disease
18
Fig 2 showing penile ulcers in a Nigerian with Behcet's Disease
19
Fig. 3 Pseudo-folliculitis in a Nigerian with Behcet’s Disease.
20
Fig 4. Photograph of the eye showing cataract formation and extensive posterior synechae following
recurrent uveitis in a Nigerian with Behcet's disease.
21
Fig 5.
Photograph of the eye of a Nigerian with Behcet's disease showing extensive vascular
sheathing and retinal pigment attenuation as well as well as epithelial atrophy and macula hole
22
23
Fig 5. Ultrasound scan of the eyes showing extensive vitritis with posterior vitreous
detachment and vitreo-retinal traction in a Nigerian with Behcet’s Disease.
24
25