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Sarcoidosis

See also in: External and Internal Eye,Hair and Scalp,Oral Mucosal Lesion
Contributors: Jeffrey M. Cohen MD, Paritosh Prasad MD, Belinda Tan MD, PhD, Susan Burgin MD, Noah Craft MD, PhD
Other Resources UpToDate PubMed

Synopsis

Sarcoidosis is an immune-mediated systemic disorder typified by granuloma formation of the lung parenchyma and the skin, but it can affect many other organs. The inciting immune activating agent remains unknown (hypotheses include autoimmune, infectious, and environmental triggers). The disease affects all ages and ethnicities and both sexes, with peak incidence demonstrating a bimodal age distribution: ages 25-35 and 45-65. It is most commonly observed in women. Cutaneous disease is often the first sign of systemic sarcoidosis.

Sarcoidosis commonly presents with abnormalities identified incidentally on chest radiography. Although the disease can affect different organs, systemic symptoms such as fever, night sweats, and weight loss are common. Sarcoidosis can affect the lungs, peripheral lymph nodes, heart, kidneys, gastrointestinal tract, central nervous system (CNS), liver, spleen, bone, muscle, and endocrine glands. Approximately 90% of patients will have lung involvement. Pulmonary fibrosis and bronchiolectasis result in "honeycombing" of the lung and represent end-stage lung disease due to chronic granulomatous inflammation. Hilar lymphadenopathy is asymptomatic and affects 90% of patients. Approximately 10% of patients have hypercalcemia.

Ten to thirty percent of patients will present with Löfgren syndrome with arthritis, erythema nodosum, and bilateral hilar adenopathy. Women more commonly have erythema nodosum, and men more commonly have ankle periarticular inflammation or arthritis. Two-thirds of patients achieve remission within a decade with few consequences, with the majority within 3 years. The remaining one-third have progressive disease with significant organ impairment.

Approximately 25% of patients will have cutaneous involvement and, commonly, many patients have skin-limited disease. Asymptomatic red-brown dermal papules and/or plaques that favor the face, neck, upper extremities, and upper trunk are the most common specific cutaneous sarcoid lesions. There are several other morphologic variants of cutaneous sarcoidosis:
  • Lupus pernio – Violaceous papules and plaques that are most commonly found on areas affected by the cold (hence, the name pernio), such as the nose, ears, and cheeks. In contrast to other cutaneous sarcoid lesions, lupus pernio can result in scarring.
  • Verrucous lupus – Presents as verrucous lesions that are easily misdiagnosed as warts or squamous cell carcinoma.
  • Angiolupoid sarcoidosis – Presents as erythematous to violaceous papules or nodules on the lateral nose and near the medial canthus. These lesions can have surrounding telangiectasia.
  • Psoriasiform sarcoidosis – Rare variant that presents with plaques that look like psoriasis.
  • Tattoo sarcoidosis – Sarcoid papules and nodules can present within tattoos. This can also occur within other scars.
  • Atrophic sarcoidosis – Presents as hypopigmented, shiny, or wrinkly plaques.
  • Hypopigmented sarcoidosis – Characterized by hypopigmented, well-demarcated plaques.
Another clinical variant is Darier-Roussy sarcoidosis, also known as subcutaneous nodular sarcoidosis, which is characterized by asymptomatic, firm, mobile subcutaneous nodules without epidermal involvement. This is often associated with systemic sarcoidosis.

Mortality is most commonly due to significant granulomatous disease in the lungs and heart, leading to respiratory failure, cardiac arrhythmias, and heart failure. CNS, liver, and renal diseases are also well-known causes of morbidity and mortality.

The pathogenesis of sarcoidosis is poorly understood. However, it is characterized by noncaseating epithelioid granulomas made up mostly of CD4+ helper T-cells, a predominantly Th1 type immune response, and elevated levels of interferon (IFN)-gamma and interleukin (IL)-2.

Some drugs and exposures have been associated with the development of sarcoidosis and sarcoid-like granulomatosis. Patients undergoing antiviral therapy for chronic hepatitis C – both monotherapy with IFN-alpha and combination therapy with IFN-alpha and ribavirin – have developed new-onset sarcoidosis or experienced reactivation of preexisting sarcoidosis during or shortly after treatment. The disease typically manifests as pulmonary and/or cutaneous sarcoidosis and follows a benign course, resolving spontaneously or within months after antiviral treatment is completed. More complicated multisystem cases, eg, involving the CNS, have been reported. The use of systemic corticosteroids to treat sarcoidosis in such patients should be considered with caution due to their adverse effects on viral loads. In addition, there have been an increasing number of reports of new-onset sarcoidosis manifesting in patients who are receiving anti-tumor necrosis factor (TNF)-alpha therapy (etanercept, infliximab, adalimumab), eg, for a rheumatologic diagnosis. This is paradoxical, because TNF-alpha inhibitors have been used to treat sarcoidosis. Disease typically resolves with discontinuation of the drug and steroid therapy. It has been reported that exposure to moderate to high levels of silica increases the risk for sarcoidosis. This association is more common in men due to occupational exposure.

Pediatric Patient Considerations:
Sarcoidosis is an uncommon disease in pediatric patients and is extremely rare in children younger than 6 years. When sarcoidosis presents in children younger than 6 years, it is characterized by a triad of skin rash, uveitis, and arthritis without intrathoracic involvement. In adolescents, the cutaneous manifestations of sarcoidosis are similar to those seen in adults, with the exception of lupus pernio and erythema nodosum, which are rare in that age group.

Codes

ICD10CM:
D86.3 – Sarcoidosis of skin

SNOMEDCT:
31541009 – Sarcoidosis

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

Sarcoidosis is a diagnosis of exclusion, on a clinical and histologic level. Clinically, sarcoid papules, nodules, and plaques are not unique, and a histologic evaluation is often required. The histologic differential is broad, and detailed histologic findings are beyond the scope of this text. Special stains for acid-fast and fungal organisms and tissue cultures should be obtained when necessary.

The following is a clinical differential of sarcoidosis:

Granulomatous lung disease:
Sarcoidosis can involve multiple other organs including the heart, eyes, CNS, gastrointestinal system, and renal system, and as such the differential diagnosis is protean.

Papules:
Nodules:
Plaques:
Pediatric Patient Differential Diagnosis:
Polyarticular juvenile idiopathic arthritis must be considered in the differential, given the combination of skin, eye, and joint manifestations in children younger than 6 years.

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Therapy

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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References

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Last Reviewed:07/22/2020
Last Updated:07/29/2020
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Sarcoidosis
See also in: External and Internal Eye,Hair and Scalp,Oral Mucosal Lesion
Sarcoidosis (Common Skin Lesions) : Face, Neck, Arms
Clinical image of Sarcoidosis
A close-up of a cluster of smooth reddish-brown papules arranged in an annulus.
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