eMedicine Specialties > Dermatology > Reactive & Inflammatory Dermatoses

Sarcoidosis

Author: Karen Podlipsky Gould, MD, Physician, Private Practice
Coauthor(s): Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine
Contributor Information and Disclosures

Updated: Sep 8, 2009

Introduction

Background

Sarcoidosis is characterized by noncaseating epithelioid granulomas that may affect any organ system. Although Jonathan Hutchinson described the first case in 1869, the etiology of the disease is still unknown. The disease most commonly involves granuloma formation in the lungs. Other commonly involved organ systems include the lymph nodes (especially the intrathoracic nodes); the skin; the eyes; the liver; the heart; and the nervous, musculoskeletal, renal, and endocrine systems.

For more information from eMedicine, see Sarcoidosis (pediatric focus) and Sarcoidosis (ophthalmology focus).

Pathophysiology

The etiology of sarcoidosis is unknown, but several immune aberrations have been noted and are thought to play a role in its pathogenesis. Studies have shown an increase in B-cell activity with hypergammaglobulinemia noted in about one half of patients and in nonspecific immune-complex formation. Reduced delayed-type hypersensitivity responses are also found in many patients with sarcoidosis. Cutaneous anergy to tuberculin intradermal testing occurs in two thirds of patients. Immune dysregulation has been theorized to be due to a persistent antigen of low virulence that is poorly cleared by the immune system, leading to a chronic T cell of the Th1 subtype response, which results in granuloma formation. Medications that increase the Th1 response, such as interferon, have been reported to trigger or exacerbate sarcoidosis.¹  The gli -1 oncogene has been found to be highly expressed in persons with granulomatous skin diseases, including sarcoidosis.²

Proposed antigens fall into 3 categories that include infectious, environmental, and autoantigens. The most common infectious agents implicated are Mycobacterium tuberculosis, Mycoplasma species, Corynebacteria species, spirochetes, atypical mycobacteria, Propionibacterium acnes, Borrelia burgdorferi, herpes simplex virus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, coxsackievirus, rubella virus, Histoplasma species, Cryptococcus species, coccidioidomycosis, and sporotrichosis. Environmental antigens implicated include metals (eg, zirconium, aluminum, beryllium), organic dusts (eg, pine, pollen), and inorganic dusts (eg, clay, soil, talc). Heat shock protein has also been implicated.

Frequency

United States

The prevalence of sarcoidosis is 1-40 cases per 100,000 population. In whites, the annual incidence is 10-14 cases per 100,000 population, whereas in African Americans, especially women, the annual incidence is much higher, at 35.5-64 cases per 100,000 population.³

International

Sarcoidosis affects people worldwide. It is found in every country and every race, although the incidence varies dramatically. In Europe, the disease affects whites more commonly than other races, and it affects Western Europeans more than Eastern Europeans. Scandinavians have one of the highest incidence rates at 64 cases per 100,000 population, whereas, in Poland, the incidence is 3 cases per 100,000 population. The disease is rare in Eskimos, Southeast Asians, New Zealand Maoris, and native Canadian populations.

Mortality/Morbidity

The course of sarcoidosis is variable, ranging from self-limited acute disease to a chronic debilitating disease that may result in death. Spontaneous remissions occur in nearly two thirds of patients, but 10-30% of patients have a more chronic or progressive course.

• The mortality rate is 1-6%. Sarcoidosis can lead to death from severe involvement of lung parenchyma leading to pulmonary fibrosis and respiratory failure and from myocardial involvement leading to arrhythmias and cardiac failure.
• Other causes of significant morbidity and mortality include CNS involvement, blindness, pulmonary hemorrhage, renal insufficiency, hypopituitarism, and liver disease.

Race

In the United States, the disease is 10-17 times more common in African Americans than in whites.³ Whites present more commonly with earlier stage disease, usually bilateral hilar adenopathy (see Media File 2); African Americans present at an earlier age with later stage disease.

Sex

Sarcoidosis affects both men and women, but it seems to be most prevalent among African American women. The incidence of sarcoidosis is highest in African American women followed in order by African American men, white women, and white men.

Age

Although sarcoidosis can appear at any age, a bimodal age distribution is seen, which peaks between ages 25-35 and 45-65 years.

Clinical

History

Because sarcoidosis can involve any organ system, the clinical presentation is often variable. Patients most commonly present in winter and early spring, which suggests a possible environmental trigger. The onset is usually insidious, and findings may be discovered on routine chest radiographs. Cutaneous involvement is seen in 25% of patients with sarcoidosis; it usually accompanies systemic involvement but may be the only site of involvement.

• General manifestations: One third of patients have constitutional symptoms, such as fever, fatigue, and weight loss.
• Pulmonary system: The lungs are affected in most patients. Symptoms occur in one third to one half of patients and most commonly include dyspnea, dry cough, and chest tightness or pain. The disease can progress to parenchymal infiltration and, ultimately, irreversible fibrosis.
• Lymphatic system: One third of patients with sarcoidosis have palpable lymph nodes that are moveable and nontender. Right paratracheal lymph node enlargement is most commonly seen, followed next by cervical nodes.
• Ocular involvement: Anterior uveitis is the most common finding, which may be associated with fever and parotid swelling (also called uveoparotid fever). Chronic uveitis, most commonly occurring in African Americans, can lead to adhesions, glaucoma, cataract formation, and blindness. Although uveitis is most common, any part of the eye may be affected.
• Neurosarcoidosis: Involvement of the nervous system occurs in fewer than 10% of patients; it may be lethal. The disease can affect any part of the nervous system. Seventh cranial nerve palsy is the most frequent finding. The pituitary gland and the hypothalamus may be involved.
• Myocardial involvement: Clinically apparent cardiac involvement occurs in 5% of patients in the United States.
• Other organs may be involved: Elevated liver function tests suggestive of hepatic dysfunction, arthritis, proximal muscle weakness, anemia, leukopenia, hypercalcemia, diabetes insipidus, and renal failure may be noted.

Physical

• EN is a hypersensitivity reaction resulting from exposure to a variety of infections or inflammatory disorders.
  • EN is usually an acute, self-limiting process and rarely requires treatment. Recurrences are uncommon. Tender, erythematous nodules are usually present on the extremities, most commonly on the anterior surface of the tibia. EN is more common in European, especially Scandinavian, women of childbearing age than in other people.
  • Löfgren syndrome is EN in conjunction with unilateral or bilateral hilar and/or right paratracheal lymphadenopathy, anterior uveitis, and/or polyarthritis. Other symptoms include fever, periarticular ankle inflammation, arthralgias, and pulmonary involvement. Löfgren syndrome is usually an acute disease with an excellent prognosis, typically resolving spontaneously in 6-8 weeks. Pulmonologists, ophthalmologists, and rheumatologists often define this syndrome differently, describing varying combinations of arthritis, arthralgia, uveitis, EN, hilar adenopathy, and/or other clinical findings.
• Lupus pernio, first described by Besnier in 1889, is a striking manifestation of sarcoidal skin lesions.
  • Lupus pernio is characterized by red-to-purple or violaceous, indurated plaques and nodules that usually affect the nose, the cheeks, the ears, and the lips, but it can appear on the dorsa of the hands, the fingers, the toes, and the forehead.
  • Lupus pernio is usually more common in black women with long-standing systemic, usually pulmonary, sarcoidosis than in other people. It is also commonly seen with chronic uveitis and bone cysts. The course is usually chronic, and severe cosmetic disfigurement may result.
  • Lupus pernio, especially involving the nasal rim, has been associated with granulomatous involvement of the upper respiratory tract (50%) and lungs (75%).⁴
• Macular or papular sarcoidosis is the most common lesion seen in cutaneous sarcoidosis, especially in African American women. Granulomatous acne rosacea may mimic sarcoidosis clinically and histopathologically.
  • Usually, lesions are asymptomatic, red-brown macules and papules commonly involving the face, the periorbital areas, the nasolabial folds, and/or the extensor surfaces.
  • Lesions usually resolve without scarring, although scarring may occur.
  • These lesions may also occur in acute sarcoidosis.
• Plaque sarcoidosis is characterized by round-to-oval, red-brown to purple infiltrated plaques; the center of the plaque may be atrophic (see Media File 5).

• Some plaques may even appear scaly and can be confused with lesions of psoriasis or lichen planus.
• They most commonly occur on the extremities, the face, the scalp, the back, and the buttocks, and they may have an annular appearance. The distribution is usually symmetric.
• Angiolupoid sarcoidosis is a subtype that has a similar appearance but has large telangiectatic vessels in addition to the characteristics mentioned above.
• This form of cutaneous involvement is usually chronic; most patients have the disease for more than 2 years. Lesions can heal with scarring, and, if plaques involve the scalp, they may lead to alopecia. Patients with plaque lesions usually have more severe systemic involvement.
• Subcutaneous nodular sarcoidosis is also called Darier-Roussy sarcoidosis.
  • Lesions are usually nontender, firm, oval, flesh-colored or violaceous nodules that are 0.5-2 cm in diameter. They are commonly found on the extremities or the trunk.
  • These lesions usually appear in the beginning of the disease. These patients often have nonsevere systemic disease. In some patients, the nodules resolve spontaneously.
• Infiltration of scars may occur (see Media File 9). Scars from previous trauma, surgery, venipuncture, or tattoo may become infiltrated and show a red or purple color. These lesions may be tender.
• Sarcoidosis is called the "great imitator" because it can have almost any morphology.⁵ Other rare lesions of cutaneous sarcoidosis are ichthyosiform,⁶ lichenoid, vasculitic,⁷ psoriasiform, erythrodermic, verrucous, papillomatous, and ulcerative lesions.

Causes

The exact etiology of sarcoidosis has not been clearly defined. Genetic as well as environmental factors are thought to play a role in the disease process. Sarcoidosis is thought to result from exposure of a genetically susceptible host to specific environmental agents that the immune system is unable to clear effectively.

• Environmental influence
  • Numerous geographically localized outbreaks have been reported and suggest the possibility of an infectious agent or shared environmental exposure as the causative agents. Infectious organisms, such as mycobacteria, can induce granulomatous inflammation. Many organisms have been linked to sarcoidosis, including Mycoplasma species; Borrelia burgdorferi; Propionibacterium acnes; fungi, such as Histoplasma and Cryptococcus species; viruses, such as Epstein-Barr virus, cytomegalovirus, herpes simplex virus, hepatitis C virus,⁸ and rubella; and numerous other organisms.
  • Noninfectious agents, such as aluminum, zirconium, talc, pine tree pollen, and clay, have also been implicated.
• Genetic factors
  • Familial clustering of cases has been reported. Monozygotic twins are 2-4 times as likely to have the disease as dizygotic twins.⁹
  • Certain HLA associations have been demonstrated; the most common allele found in sarcoidosis is HLA-B8. Other associated alleles include HLA-A1 and HLA-DR3.
  • Two genes that are commonly found in female whites were found to be associated with EN in a study of sarcoidosis patients: a variant in the promoter of TNF and a variant in intron 1 of lymphotoxin-alpha, an adjacent gene.¹⁰

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