Continuing Medical Education
Sarcoidosis,☆☆,

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Abstract

Sarcoidosis is a systemic noncaseating granulomatous disorder of unknown origin. The cutaneous manifestations of sarcoidosis often enable the dermatologist to be the first physician to make the diagnosis. This article reviews essential sarcoidosis pathophysiology, clinical polymorphisms, systemic evaluation, and treatment modalities for cutaneous sarcoidosis to further enhance the dermatologist's understanding of this disease entity. (J Am Acad Dermatol 2001;44:725-43.) Learning objective: At the conclusion of this learning activity, participants should be familiar with the theories of the pathogenesis of sarcoidosis, its cutaneous manifestations, its various syndromes and associations, and its presentation in children. Participants should also be more knowledgeable about diagnostic evaluation, measurement of disease progression, treatment modalities, and the prognosis and mortality data of sarcoidosis.

Section snippets

Definition

In Greek, sarcoidosis means a fleshlike condition (sarco means “flesh,” eidos means “like,” and osis means “condition.”)1 In contemporary times, sarcoidosis is a multisystem disorder of unknown origin, characterized by the accumulation of lymphocytes and mononuclear phagocytes that induce the formation of noncaseating epithelioid granulomas with secondary derangement of normal tissue or organ anatomy and function. Evidence of sarcoidosis lasting longer than 2 years designates it as chronic.2, 3

Epidemiology

Sarcoidosis affects all races, both sexes, and all ages. Most commonly it presents in winter and early spring.4 It usually peaks between the ages of 25 and 35 years; a second peak occurs in women aged 45 to 65 years.1, 5 Cases affecting African Americans have a tendency to be more acute and severe than in other races, whereas cases affecting white persons have a tendency to be asymptomatic with a more favorable prognosis.6

The worldwide incidence of sarcoidosis is reported as follows: Sweden,

Etiology

The origin of sarcoidosis remains unknown.12, 13 Many postulations abound as to whether the cause is multifactorial or due to a single antigen-driven disease that has not yet been determined. The cause has been thought to be elusive because sarcoidosis is a disease with the following characteristic flaws: polymorphic disease presentations, overlap with other diseases, paucity of systematic epidemiologic investigations of cause, diagnostic access bias, misclassification of the disease because of

Cutaneous manifestations

On average, 25% of sarcoidosis cases have cutaneous involvement that can occur at any stage; however, most often cutaneous involvement occurs at onset of the disease.13, 54, 55 In general specific skin lesions have no prognostic significance, do not show any correlation with the extent of systemic involvement, and do not indicate a more serious form of sarcoidosis.55, 56, 57 This is with the exception of erythema nodosum (EN), which has been shown to have a good prognosis because of its

Clinical polymorphisms of systemic sarcoidosis

In patients with sarcoidosis, one third can present with nonspecific constitutional complaints including fever, fatigue, malaise, and weight loss.62 Postsarcoidosis chronic fatigue syndrome may be difficult to separate from low-grade persistent sarcoidosis.100 Sarcoidosis is also in the differential diagnosis of a fever of unknown origin.62 Other symptoms can be associated with the specific organ system affected. Johns and Michelle15 noted that extrathoracic manifestations of sarcoidosis are

Differential diagnosis

The differential diagnosis for systemic sarcoidosis includes foreign body granuloma, infection, autoimmune disorders, and neoplasia.13 Lymphoma,156 Wegener's granulomatosis,157 primary biliary cirrhosis,158 Churg-Strauss syndrome,13 M tuberculosis,13 atypical mycobacteria such as M avium and M leprosum,159 histoplasmosis,68 coccidioidomycosis,68 brucellosis,13 chlamydia,160 tularemia,68 Treponema and Borrelia burgdorferi,161 as well as leishmaniasis13 and toxoplasmosis68 may give similar

Childhood sarcoidosis

Infants and young children (9-15 years) present most frequently with lymph node, skin, joint, and eye involvement without the typical lung disease initially.165 The classic presentation is with the triad of arthritis, skin lesions, and uveitis.166 Spontaneous resolution occurs more often in children, but a significant number of small children have a residual morbidity.165 It affects both sexes equally, and almost all children with sarcoidosis are symptomatic with vague complaints, including

Sarcoidosis syndromes

Because of the many polymorphisms of sarcoidosis, there are several syndromes incorporating specific manifestations of the disease. Löfgren's syndrome, frequent in Irish, Scandinavian, and Puerto Rican female patients, consists of acute sarcoidosis, EN, migratory polyarthritis, fever, and iritis.9, 56, 95, 171 It usually has a good prognosis with a self-limiting course and resolution without therapy.95 Sarcoidosis, Darier-Roussy type, is the presence of subcutaneous nodules of the trunk and

Sarcoidosis associations

Sarcoidosis has been found in association with autoimmune and neoplastic disorders as well as several medications. These disorders may be coincidental or represent true alliances.12 Autoimmune disorders found in association with sarcoidosis are possibly related to the overall immune dysregulation with polyclonal B-cell production of antibodies found in sarcoidosis. The associations reported include autoimmune hemolytic anemia, autoimmune idiopathic thrombocytopenia, and Sjögren's syndrome173;

Diagnostic evaluation

There is no diagnostic test for sarcoidosis; hence it is a diagnosis of exclusion. It is important to obtain a complete history with emphasis on occupational and environmental exposure. The emphasis during physical examination should be placed on the skin, lungs, eyes, nerves, and heart. If there are any abnormal findings suggestive of sarcoidosis, a biopsy (skin, peritracheal nodes, or salivary glands) should be performed to obtain histologic confirmation of noncaseating granulomas,

Measurement of disease progression

ACE is normally produced by endothelial cells in the kidney and in sarcoidosis by T-cell—stimulated epithelioid cells at the periphery of the granulomas. ACE is not specific for sarcoidosis and is elevated in leprosy, alcoholic liver disease (cirrhosis), α1-anti-trypsin deficiency, diabetes mellitus, Kaposi's sarcoma/HIV, Melkersson-Rosenthal syndrome, silicosis, hypersensitivity pneumonitis, Gaucher's syndrome, primary biliary cirrhosis, histoplasmosis, and asbestosis.15, 195, 218, 219 There

Treatment

The indication for treatment of systemic sarcoidosis depends on disabling symptoms, organ derangement or dysfunction, and laboratory and ancillary study results.9 Glucocorticoids are the first-line treatment.13 In chronic disease nonsteroidal immunosuppressive agents are used to avoid long-term corticosteroid-induced side effects.234 The agents most often used are antimalarials, methotrexate, azathioprine, chlorambucil, cyclophosphamide, and cyclosporine.3, 62, 234 The data on immunosuppressive

Prognosis/mortality

Up to 60% of patients with sarcoidosis experience spontaneous resolution, and an additional 10% to 20% of patients have resolution with corticosteroid use.267 Patients with EN and acute inflammatory manifestations of sarcoidosis appear to have a high rate of spontaneous remissions (>80%).58, 60 The prognosis of cutaneous sarcoidosis depends on systemic involvement.55 Relapses as treatment is withdrawn are frequent, especially in African American patients, who tend to have more severe and more

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    No funds were received for the preparation of this article and none of the authors have any competing interests to disclose.

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    J Am Acad Dermatol 2001;44:725-43

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