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  • Christine Ahn MD
    Carl Allen DDS, MSD
    Brandon Ayres MD
    Howard P. Baden MD
    Robert Baran MD
    Keira Barr MD
    Gregory J. Basura MD, Ph.D
    Donald Belsito MD
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Contributors: Paritosh Prasad MD, Belinda Tan MD, PhD, Noah Craft MD, PhD
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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 (autoimmune vs. infectious vs. environmental). The disease affects all ages, ethnicities, and both sexes, with peak incidence demonstrating a bimodal age distribution: ages 25-35 and 45-65. It is most commonly observed in black women in their fourth decade.

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, nervous system, 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. Less common manifestations include sarcoid lesions with epidermal change such as scale, hypopigmentation, subcutaneous nodules, cicatricial alopecia, ulceration, and scar. May occur in tattoos.

Mortality is most commonly due to significant granulomatous disease in the lungs and heart, leading to respiratory failure, cardiac arrhythmias, and heart failure. Central nervous system (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 IL-2.

  • Löfgren syndrome – Erythema nodosum with fever, hilar adenopathy, anterior uveitis, and migrating polyarthritis.
  • Lupus pernio – Violaceous papules and plaques that are most commonly found on areas affected by the cold (hence, the name pernio): nose, ears, cheeks. Approximately 75% of patients with lupus pernio have chronic sarcoidosis of the lungs, and approximately 50% of patients will have upper respiratory tract involvement. Cystic lesions in the distal portion of the phalanges can be seen. In contrast to other cutaneous sarcoid lesions, lupus pernio can result in scarring.
  • Darier-Roussy disease – Also known as subcutaneous nodular sarcoidosis, this disease is characterized by asymptomatic, firm, mobile subcutaneous nodules without epidermal involvement.
  • Heerfordt syndrome – Fever, uveitis, parotid gland enlargement, and cranial nerve palsies. The facial nerve is often affected.
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 re-activation of pre-existing 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 with some success. 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 males 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.


D86.3 – Sarcoidosis of skin

31541009 – Sarcoidosis

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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, nervous system, gastrointestinal system, and renal system, and as such the differential diagnosis is protean.

Pediatric Patient Differential Diagnosis:
Polyarticular juvenile rheumatoid 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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Last Reviewed: 11/18/2016
Last Updated: 10/26/2017
Copyright © 2018 VisualDx®. All rights reserved.
See also in: External and Internal Eye,Hair and Scalp,Oral Mucosal Lesion
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Sarcoidosis : Cough, Rash, ACE elevated, Face, Hilar lymphadenopathy, Erythema nodosum, Anorexia, Arthralgia, Dyspnea, Firm papules
Clinical image of Sarcoidosis
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