Answer: C

Sarcoidosis is a noninfectious granulomatous disease that can affect any organ system, although it has a particularly strong predilection for the lungs, lymph nodes, and skin.  Cutaneous lesions, which may be the presenting sign or develop later in the disease, occur in 25% to 30% of patients.1 Cutaneous lesions, however, are rarely the only manifestation of this disease. When present, cutaneous sarcoidosis lesions are most often red-to-brown to violaceous papules and plaques. Of note, sarcoidosis has a unique propensity to develop in areas of trauma, so plaques are common on the knees, elbows, and within tattoos.2 However, sarcoidosis can develop anywhere in and on the skin and lesion morphology is protean.1

Lesions on the face are often symmetrically distributed affecting periocular and nasal areas. The term lupus pernio is used to describe a characteristic presentation with indurated violaceous papulonodules and/or plaques that develop on the nose, cheeks, and ears.  Identifying lupus pernio is important as it strongly suggests lung and upper respiratory tract involvement.

Continue Reading

The age of onset of sarcoidosis is bimodal, occurring most commonly between the ages of 25 to 35 years and then between 45 and 65 years. Blacks are at a higher risk of developing the disease, with an estimated incidence of 39 per 100,000 compared with an incidence of 5 per 100,000 in whites. In addition, blacks are more severely affected, with an age-adjusted mortality rate 12 times higher than that seen in whites.3

There is a strong genetic component, with an 80-fold increase in risk demonstrated in monozygotic twins.4 The pathogenesis of sarcoidosis involves a genetic susceptibility to characteristic granuloma formation triggered by exposure to currently unknown antigens. Identification of specific T-cell clones from tissue samples supports the theory of an antigenic trigger; however, it is unclear whether the antigens are of an autoimmune, infectious, or foreign body etiology.

Sarcoidal granuloma formation is similar to other granulomatous disorders, involving T-helper 1 (Th1) cells that produce various cytokines including interleukin (IL)-2, IL-12, IL-18 and interferon gamma, which act to recruit macrophages. Tumor necrosis factor (TNF) alpha production within the granuloma guides the fusion of epithelioid histiocytes, forming the classic multinucleated giant cells.5 Of interest, sarcoidal granulomas also incorporate the innate immune system and Th17 cell subtypes into their pathogenesis.6

Sarcoidosis is the great imitator and may resemble many other types of lesions including annular, psoriasiform, ichthyosiform, ulcerative, hypopigmented, subcutaneous, and erythrodermic lesions.2,7 Sarcoidosis, therefore, is a diagnosis that relies on a combination of clinical and laboratory evidence. Histologic exam will show the classic noncaseating granulomas throughout the dermis with epithelioid cells and fused multinucleated giant cells. These epithelioid tubercles and the paucity of a lymphocytic infiltrate help to differentiate sarcoidal granulomas from other granulomatous disorders. Asteroid and Schaumann bodies are inclusions sometimes found within the giant cells, but are not specific for sarcoidosis. It is important that the tissue evaluation include a variety of other studies to exclude other causes of granulomatous disease. 

The clinical differential diagnosis of cutaneous sarcoidosis is vast and variable depending upon lesion morphology. Fortunately, the finding of granulomas histologically helps narrow the possibilities. Noninfectious granulomatous disorders to be considered include granuloma annulare, necrobiosis lipoidica, annular elastocytic giant cell granuloma, cutaneous Crohn disease, palisading neutrophilic and granulomatous dermatitis, and rheumatoid nodules. Foreign body reactions from exposure to beryllium, silica, zirconium, and tattoo ink should also be part of the differential diagnosis. Infectious granulomatous disease can be due to mycobacterium or fungal organisms. Because these other disorders must be excluded, special stains, polymerase chain reaction, tissue cultures, and polarization are needed; sarcoidosis can be considered a “diagnosis of exclusion.”1

Recognition of both the cutaneous and extracutaneous manifestations is important in the management of patients with sarcoidosis, as any organ system can be affected. Pulmonary involvement is the most common, occurring in 90% of patients, and is associated with symptoms such as cough, dyspnea, and wheezing. In addition, all patients should be screened for signs and symptoms associated with other conditions including uveitis, cardiac abnormalities, cranial neuropathies, hepatic disease, endocrine dysfunction, renal disease, and musculoskeletal disorders. As mentioned, cutaneous disease is highly variable, but identification of skin lesions can readily aid in the diagnosis as a skin biopsy is more easily performed than biopsies of other organ systems.7 Therefore, coordination between specialists is necessary for diagnosis and management. A complete investigation should include chest x-ray, pulmonary function testing, ophthalmologic evaluation, electrocardiogram, tuberculin skin testing, and laboratory tests including thyroid function, complete blood count, and comprehensive metabolic panel including calcium and vitamin D levels.1

Treatment is dictated by the organ(s) involved and disease severity. Since systemic disease is usually present, systemic therapy is usually needed; the most commonly used agents include prednisone, as well as various steroid-sparing immune modulators such as methotrexate and TNF inhibitors.1,8 Cutaneous lesions may respond to systemic therapy.  However, skin-directed therapy may be needed either in combination with systemic therapy or as monotherapy if systemic therapy is not indicated. All classes of topical steroids, as well as intralesional injection of triamcinolone, are commonly used for various lesions in different anatomic sites. Antimalarial therapy, most commonly with hydroxychloroquine can also be useful; beneficial effects are usually not seen for 2 to 3 months. 

Evaluation of the patient revealed significant pulmonary disease. Skin biopsy showed “naked” epithelioid granulomas in the dermis with only a few surrounding lymphocytes and some peripheral fibrosis. Special stains and tissue cultures were negative for organisms, supporting the diagnosis of sarcoidosis. The chest x-ray showed bilateral hilar lymphadenopathy with some interstitial changes, which is also consistent with a diagnosis of sarcoidosis. His cutaneous lesions improved with the use of prednisone for his pulmonary disease and judiciously applied topical alclometasone cream.

Click to the next page for Case 2.