The frequency and clinical
features of sarcoidosis
patients with
extrapulmonary organ
involvement.
Muammer Bilir and Sevtap Sipahi
Demirkok
Istanbul University,Cerrahpasa
Medical Faculty,Internal Medicine
Backgound



Sarcoidosis is a multisystemic granulomatous
disease of unknown aetiology
Since sarcoidosis is a multiorgan
disease,patients may complain of a variety of
symptoms that may complicate diagnosis.
Extrapulmonary involvement is a major cause
of morbidity
.

Extrapulmonary organ involvement is
also an important criteria for therapy
as well.
Objective
We aimed (i) to investigate the organs
most affected in a cohort of 212
sarcoidosis patients.(ii) to analyse the
clinical,demographic and diagnostic
features of sarcoidosis pts with
extrapulmonary symptoms at onset.
Material and Methods


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109 sarcoidosis cases with extrapulmonary
symptoms (1985-2005) at onset were included
in the study.
The diagnosis of sarcoidosis was established
by the presence of noncaseating granulomas
on the histological examination of at least one
tissue specimen.
The demographic features, presenting clinical
features, initial diagnostic methods for each
patient were analyzed.
Results
The study population included 83 female and 26
male patients with the mean age of
42.48±12.10 yrs.
 8.3% of patients with extrapulmonary
symptoms had a normal chest x-ray
 54.1% presented with bilateral hilar
adenopathy
 33% with stage II
 4.6 % with stage III
The frequency of involvement of
various organs
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51.4% erythema nodosum (EN)
24.8% skin lesions other than EN, lupus pernio
and subcutaneous nodul
17.4% peripheral lymphadenopathy
16.5% ocular involvement
8% hepatomegaly
5% miyaljia
4.8% hipercalcemia
The frequency of involvement of
various organs



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8.3% Lupus Pernio
8.3% Subcutaneous nodular lesion
3.6% lacrimal ve parotis gland
involvement
2.8% Skar infiltration
The frequency of involvement of
various organs

4.6% Neurologic involvement
.1.8% Fasiyal Paralizi
.0.9% Diabet İnsipidus
.0.9% Empty cella
.0.9% Leptomeningeal involvement
The frequency of involvement of
various organs

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0.9% Glomerulonefritis
0.9% Gastric ve omentum major
involvement
0.9% Nefrocalcinosis
*The total number of observations is higher than the
number of patients because some patients had more than
one type of organ involvement
Initial diagnostic methods

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Transbronchial biopsy (52.3%),
Mediastinoscopy (22% )
Skin biopsy (27.5%)
Peripheral lymph node biopsy (27.5%)
Kveim biopsy(%7.3)
Liver biopsy(%5.5)
Nasal biopsy(%1.8)
Scalen lymph node biopsy (%1.8)
Bone marrow biopsy(%0.9)
*The total number of observations is higher than the number of patients
because some patients had more than one type of organ involvement
.

Extrapulmonary involvement during the
course of systemic sarcoidosis is
observed in 9-37% of the patients.
Wu J,Schift Rashcouskay K. Sarcoidosis.
American Family Phscian Vol:70,No:2,2004
Rizzato G. Extrapulmonary presentation of sarcoidosis. Cur Opin Pulm Med.
2001 Sep;7(5):295-7
Rizzato G, Palmieri G, Agrati AM, Zanussi C. The organ-specific
extrapulmonary presentation of sarcoidosis: a frequent occurrence but a
challenge to an early diagnosis. A 3-year-long prospective observational study.
Sarcoidosis Vasc Diffuse Lung Dis. 2004 Jun;21(2):119-26
.


The frequency of extrapulmonary involvement
was approximately 50% in our series.
Variations in the frequency of extrapulmonary
involvement in sarcoidosis in the world
literature might be due
ethnicity,geophraphy,enviromental factors and
difference in the number of asyptomatic
patient.
.


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Variations in the selection of patients into
the study(retrospective/prospective)
Lack of a precise standard forms in the
follow-up of sarcoidosis patients
No further evaluation of the organ
involvement in asyptomatic patients.
Lack of a precise standard diagnostic
algorithms

The mean age of sarcoidosis was reported as
40.2±12.8 years in Turkey.
Sevtap Sipahi Demirkok, Metin Basaranoglu, Eylem Deniz Akinci and
Tuncer Karayel. Analysis of 275 patients with sarcoidosis over a 38 year
period; a single institution experience Respiratory
Medicine,doi:10.1016/j.rmed.2006.11.013 (in press).
Tabak L, Kılıçaslan Z,Kıyan E,Erelel M,Çuhadaroglu Ç,Arseven
O,Erkan F,Ece T.147 Sarkoidoz hastasının klinik özellikleri. Solunum
3:80-85,2001
Baran A, Özşeker F,Güneylioğlu D,Bilgin S,Arslan S,Uyanusta Ç,Akkaya
E.Sarkoidoz:Yedi yıllık deneyim. Toraks Dergisi, 2004 5(3): 160-5
.


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In our cohort group, 49.6% of the patients were
aged 20-40 years .22% of the patients were
distributed between 41-50 years of age
While in our cohort group the female-male ratio
was 3/1, this ratio was 4/1 in the subgroup
Extrapulmonary involvement did not show an
effect on the clustering of gender and age
.

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The most frequent skin lesion in our
study was erythema nodosum ( 29.6 %)
The frequency of EN was 51.4% in the
group with extrapulmonary involvement
The frequency of arthralgia was 18.4% in
our cohort ,while the frequency arthralgia
associated with EN was 45%
.

The highest incidence in EN and Löfgren
syndrome was reported from north
European and Spain(30% /40%)
Mana J, Gomez-Vaquero C, Montero A et al. Löfgren’s syndrome revisited: a
study of 186 patients. Am. J. Med. 1999; 107: 240–5.
Mana J, Badrinas et al.Sarcoidosis in Spain.Sarcoidosi.1992;9:118-122
Veien NK, Stahl D, Brodthagen H: Cutaneous sarcoidosis in Caucasians, J Am
Acad Dermatol, 16: 534-540, 1987.
.

The frequency of EN and Löfgren
syndrome in the United States was
reported in 8.3-25% of the patients.
Baughman R, Teirstein A,, Judson A,
Clinical Characteristics of Patients in a Case Control Study of
Sarcoidosis Am. J. Respir. Crit. Care Med., Volume 164, Number 10,
November 2001, 1885-1889
.

EN and Löfgren’s syndrome were rarely
reported in south Asia, in east India and
in Japon
.

The incidence of Löfgren’s syndrome
was17% on avarage in a woldwide
series which is as similar as our study
series
Teirstein AS, Lesser M. Worldwide distribution and epidemiology of
sarcoidosis. In: James DG, editor. Sarcoidosis and other granulomatous
diseases of the lung. New York: Marcel Dekker; 1983. p. 101-134.
James DG, Neville E,SiltzbachLE. A worldwide review of sarcoidosis.Ann N Y
Acad Sci1976:278:321-324
Demirkök Sipahi S,Basaranoglu M,Derviş E, Bal M,Karayel T. Analyzing of 87
patients with Löfgren's syndrome and the pattern of seasonality of subacute
sarcoidosis.Respirology,Vol:11,No:4,456-461,July,2006
.
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
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Cutaneous involvement except EN during the course of
systemic sarcoidosis is observed in 9-37% of the patients (11%
in Spain,42% in India,15.8% in USA, 30% in north European
and nearly 3/1 of the patients in Turkey )
This ratio was 24.8% in our study group
Veien NK, Stahl D, Brodthagen H: Cutaneous sarcoidosis in Caucasians, J Am Acad
Dermatol, 16: 534-540, 1987.
Mana J et al. Cutaneous involvement in sarcoidosis: Relationship to systemic disease.
Arch Dermatol.1997:133:882-888.
Sharma SK et al. Clinical characteristics and clinical outcome treated with prednisolone in
106 sarcoidosis patients.J Assoc Phsycians India 2001;49:691-704
Baughman R, Teirstein A,, Judson A,
Clinical Characteristics of Patients in a Case Control Study of Sarcoidosis Am. J. Respir. Crit.
Care Med., Volume 164, Number 10, November 2001, 1885-1889
.


Lupus Pernio which is more
commonly seen with chronic type of
sarcoidosis was most observed in
north European (10%) in the world
Veien NK, Stahl D, Brodthagen H: Cutaneous sarcoidosis in Caucasians, J Am
Acad Dermatol, 16: 534-540, 1987.
.



It was reported that subcutaneous nodular
lesions were associated with either subacute
or chronic sarcoidosis.
Granulomatous skin involvement in Spain
was 19% The frequency of subcutaneos
nodular lesions was 11.8% among them.
It was 8.3% in our series.
Marcoval J, Mana J, Moreno A, Peyri J
Subcutaneous sarcoidosis--clinicopathological study of
10 cases. Br J Dermatol. 2005 Oct;153(4):790- 4.
.


The incidence of ocular involvement
varies between 20% and 30% in the
world.
The frequency of ocular involvement
was 8% in our cohort group
James DG, Angime MR.Ocular sarcodosis.In:James
DG,ed.Sarcoidosis and other granulamatous
disorders.Newyork,MarcelDekker,1994,pp:275-284.
.
The frequency of ocular
involvement was 11% in USA and
20% in Japan
Baughman R, Teirstein A,, Judson A, Clinical Characteristics of
Patients in a Case Control Study of Sarcoidosis Am. J. Respir. Crit.
Care Med., Volume 164, Number 10, November 2001, 1885-1889
Goda C, Kotake S, Sasamoto Y, Yoshikawa K Okamoto T, Matsuda H.
Clinical manifestations and diagnosis of patients with sarcoidosis
Nippon Ganka Gakkai Zasshi. 1998 Feb;102(2):106-10.
.

In a study comparing the clinical features
between the patients with sarcoidosis in
Japon and in Finland showed that the
frequency of ocular involvement was
41% vs 5% ,in Japon, and in
Finland,respectively.
Pietinalho A, Ohmichi M, The mode of presentation of sarcoidosis in Finland
and Hokkaido, Japan. A comparative analysis of 571 Finnish and 686 Japanese
patients.Sarcoidosis Vasc Diffuse Lung Dis. 1996 Sep;13(2):159-66.
.

The frequency of ocular involvement
was 3% in Italy.
Rizzato G, Palmieri G, Agrati AM, Zanussi C. The organ-specific
extrapulmonary presentation of sarcoidosis: a frequent occurrence but a
challenge to an early diagnosis. A 3-year-long prospective observational study.
Sarcoidosis Vasc Diffuse Lung Dis. 2004 Jun;21(2):119-26
.


A study followed-up sarcoidosis patients
more than two years in Turkey
demonstrated the frequency of ocular
involvement was 10%.
Sevtap Sipahi Demirkok, Metin Basaranoglu, Eylem Deniz Akinci
and Tuncer Karayel. Analysis of 275 patients with sarcoidosis over a
38 year period; a single institution experience Respiratory
Medicine,doi:10.1016/j.rmed.2006.11.013 (in press).
.

The frequency of peripheral lymph
node involvement was 5% in Japan and
8% in Italy.
Goda C, Kotake S, Sasamoto Y, Yoshikawa K Okamoto T, Matsuda H. Clinical
manifestations and diagnosis of patients with sarcoidosis Nippon Ganka Gakkai
Zasshi. 1998 Feb;102(2):106-10.
Rizzato G, Palmieri G, Agrati AM, Zanussi C. The organ-specific
extrapulmonary presentation of sarcoidosis: a frequent occurrence but a
challenge to an early diagnosis. A 3-year-long prospective observational study.
Sarcoidosis Vasc Diffuse Lung Dis. 2004 Jun;21(2):119-26
.

The frequency of peripheral lymph
node involvement in our study group
(17.4%) was more relevant with the
frequency reported in USA (15.8%)
Baughman R, Teirstein A,, Judson A,
Clinical Characteristics of Patients in a Case Control Study of Sarcoidosis Am. J.
Respir. Crit. Care Med., Volume 164, Number 10, November 2001, 1885-1889
.

Neurosarcoidosis was observed in 3-15%
of the patients in the world.


The frequency of neurosarcoidosis was
4.8% in USA.
In our study group the frequency of
neurosarcoidosis was 4.6%.

Sipahi Demirkök S, Benbir G, Ertan S.Nörosarkoidoza genel bir bakış.
Cerrahpaşa Tıp Dergisi , Cerrahpaşa Tıp Dergisi,2007:37;No:1,1-36
.


The frequency of hepatomegaly was
8% in our series .
The frequency of hepatomegaly was
11% in USA,40% in India.
Baughman R, Teirstein A,, Judson A,
Clinical Characteristics of Patients in a Case
Control Study of Sarcoidosis Am.
J. Respir. Crit. Care Med., Volume 164, Number 10, November 2001, 1885-1889
Gupta SK.Sarcoidosis: a journey through 50 years. Indian J Chest Dis Allied
Sci. 2002 Oct-Dec;44(4):247-53.
.



The frequency of cardiac involvement was
2.3% in USA and 1% in our study group.
The frequency of cardiac involvement
presented as atrioventricolar block was 10%
in Japon
Sipahi S,İlerigelen B,Bilir M,Tavşanoğlu S,Uçak D,Karayel T. Sarkoidozda sol ventrikül
fonksiyonlarının ekokardiyogafi doppler yöntemiyle değerlendirilmesi. Türkiye Klinik
Kardiyoloji(Türkish Klin Cardiol) 1999;12:123-126.
Gurkan O U, Celik,Kumbasar O,Kaya A,Doganay A. Sarcoidosis in
Turkey:1954-2004.Annals of Saudi Medicine 24(1):36-39 Jan-Feb 2004.
Yoshida Y, Morimoto S, Hiramitsu S,Incidence of cardiac sarcoidosis in Japanese patients with
high-degree atrioventricular block. Am Heart J. 1997 Sep;134(3):382-6.
Conclusions


Among skin lesions, EN was the most
frequently observed manifestation in
patients with extrapulmonary
involvement.
Although the various diagnostic methods
used in our study, transbronchial biopsy
was the method most frequently used to
diagnose sarcoidosis at onset.