Continuing Medical EducationSarcoidosis☆,☆☆,★
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
References (271)
- et al.
Sarcoidosis in Caucasians, Blacks and Asians in London
Br J Dis Chest
(1985) - et al.
Global epidemiology of sarcoidosis: what story do prevalence and incidence tell us?
Clin Chest Med
(1997) - et al.
Sarcoidosis: an updated review
J Am Acad Dermatol
(1984) - et al.
The influence of diagnostic access bias on the epidemiology of sarcoidosis: a population-based study in Rochester, Minnesota, 1935-1984
J Clin Epidemiol
(1988) - et al.
Sarcoidosis news: immunologic frontiers for new immunosuppressive strategies
Clin Immunol Immunopathol
(1998) - et al.
Enhanced expression of human metalloelastase (MMP-12) in cutaneous granulomas and macrophage migration
J Invest Dermatol
(1999) - et al.
Presence of mycobacterial DNA in sarcoidosis
Hum Pathol
(1997) - et al.
Human herpesvirus 8 in sarcoid tissues
Lancet
(1997) - et al.
Sarcoidosis in a patient with AIDS: a manifestation of immune restoration syndrome
J Am Acad Dermatol
(1999) - et al.
Cutaneous sarcoidosis in Caucasians
J Am Acad Dermatol
(1987)
Morpheaform sarcoidosis: report of three cases
J Am Acad Dermatol
Cutaneous sarcoidosis: definitions and types of lesions
Clin Dermatol
Granulomatous cheilitis in two children with sarcoidosis
J Am Acad Dermatol
Sarcoidosis with subcutaneous nodules
Am J Med
Acquired ichthyosiform erythroderma and sarcoidosis
J Am Acad Dermatol
Unilateral lower extremity edema caused by infiltrative sarcoidosis
J Am Acad Dermatol
Sarcoidosis of the vulva: a rare cutaneous manifestation
J Am Acad Dermatol
Ocular sarcoidosis
Clin Dermatol
Enigmas in sarcoidosis
West J Med
Sarcoidosis
Alternatives to corticosteriods in the treatment of sarcoidosis
Sarcoidosis Vasc Diffuse Lung Dis
Epidemiology of sarcoidosis in Catalonia: 1979-1989
Sarcoidosis Vasc Diffuse Lung Dis
Sarcoidosis: epidemiology and prognosis. A 15-year European study
Am Rev Respir Dis
Epidemiology of sarcoidosis
Sarcoidosis
Sarcoidosis
Incidence of clinically identified sarcoidosis in a northwest United States population
Sarcoidosis Vasc Diffuse Lung Dis
Racial Differences in sarcoidosis incidence: a 5-year study in a health maintenance organization
Am J Epidemiol
Sarcoidosis
N Engl J Med
The clinical management of sarcoidosis: a 50-year experience at the Johns Hopkins Hospital
Medicine
T-cell receptor variable region gene usage by CD4+ and CD8+ T cells in bronchoalveolar lavage fluid and peripheral blood of sarcoidosis patients
Proc Natl Acad Sci U S A
Update on sarcoidosis
Curr Opin Rheumatol
The riddle of sarcoidosis: have novel techniques brought any new insights as to the causative agent?
J Intern Med
Multiple benign sarcoid of the skin
Arch Dermatol
Interstitial lung diseases of unknown cause: disorders characterized by chronic inflammation of the lower respiratory tract
N Engl J Med
Circulating adhesion molecules in sarcoidosis
Clin Exp Immunol
Release of prostaglandin E2 and leukotriene B4 by alveolar macrophages from patients with sarcoidosis
Thorax
An assessment of peripheral immunity in patients with sarcoidosis using measurements of serum vitamin D3, cytokines and soluble CD23
Clin Exp Immunol
Heterogeneity of familial risk in sarcoidosis
Genet Epidemiol
Epidemiology, demographics and genetics of sarcoidosis
Semin Respir Infect
Genetic influences on sarcoidosis
Eye
The sarcoidosis map: a joint survey of clinical and immunogenetic findings in two European countries
Am J Respir Crit Care Med
HLA class II genotyping of sarcoidosis patients in Hokkaido by PCR-RFLP
Jpn J Ophthalmol
Deletion polymorphism in angiotensin I converting enzyme (ACE) gene as a genetic risk factor for sarcoidosis
Thorax
Analysis of allelic variation of TAP2 gene in sarcoidosis
Tissue Antigens
HLA-DPB polymorphisms: Glu 69 association with sarcoidosis
Eur J Immunogenet
Orosomucoid and haptoglobin types in patients with sarcoidosis
Exp Clin Immunogenet
Possible transmission of sarcoidosis via allogeneic bone marrow transplantation
Bone Marrow Transplant
Sarcoidosis: chest radiograph screening of familial contacts
Respiration
Mycobacteria and sarcoidosis
Thorax
Identification of Mycobacterium avium complex in sarcoidosis
J Clin Microbiol
Cited by (273)
Ultrasound in diagnosis of cutaneous sarcoidosis
2024, Joint Bone SpineRecalcitrant Lower Leg Ulcer
2024, American Journal of MedicineSarcoidosis: A great imitator
2019, Clinics in DermatologySarcoidosis of the Skin as an Interdisciplinary Problem
2024, Vestnik Rossiiskoi Akademii Meditsinskikh NaukJanus-kinase inhibitors in dermatology: A review of their use in psoriasis, vitiligo, systemic lupus erythematosus, hidradenitis suppurativa, dermatomyositis, lichen planus, lichen planopilaris, sarcoidosis and graft-versus-host disease
2024, Indian Journal of Dermatology, Venereology and Leprology
- ☆
No funds were received for the preparation of this article and none of the authors have any competing interests to disclose.
- ☆☆
Reprints not available from authors.
- ★
J Am Acad Dermatol 2001;44:725-43