SAN DIEGO – While it’s well known that sarcoidosis commonly affects pulmonary function, it’s perhaps less known that the disorder can be detrimental to cardiac function in approximately 5% of cases.
"A common way that patients present with cardiac sarcoidosis is with sudden cardiac death," Dr. Misha Rosenbach said at the annual meeting of the American Academy of Dermatology. "This is a terrible way to present to your doctor with a problem."
Dr. Misha Rosenbach
A multisystem disorder of unknown cause, sarcoidosis commonly affects young and middle-aged adults and frequently presents with bilateral hilar lymphadenopathy, pulmonary infiltration, and ocular and skin lesions. Other organs may be involved. The diagnosis is established when clinicoradiologic findings are supported by histologic evidence of noncaseating epithelioid cell granulomas.
"Sarcoidosis is primarily a pulmonary disease, but patients can also present with profound systemic symptoms," said Dr. Rosenbach of the departments of dermatology and internal medicine at the University of Pennsylvania, Philadelphia. "When you’re evaluating a patient with cutaneous sarcoidosis, and making a diagnosis of granulomatous disease of the skin, and looking for extracutaneous involvement, it’s important to know what else can be affected."
Although pulmonary function is affected in more than 90% of cases, other commonly affected sites include the eyes (25%-50% of cases), lymph nodes (about 33% of cases), musculoskeletal system (25%-40% of cases), endocrine system (10%-25% of cases), and liver (20%-50% of cases). The initial evaluation should consist of history and physical exam; chest x-ray; pulmonary function tests (including carbon monoxide diffusing capacity); ophthalmologic examination; complete blood count and serum chemistries (including calcium); urinalysis; EKG (plus additional testing if there is a history of palpitations); tuberculin skin test (TST) or interferon (IFN)–gamma release assay; and thyroid and vitamin D testing.
Images courtesy Dr. Misha Rosenbach
A sarcoidosis case on a patient’s arm.
"Patients with sarcoidosis often have low levels of 25-hydroxyvitamin D, but elevated levels of 1,25-dihydroxyvitamin D3," Dr. Rosenbach said. "Inappropriate supplementation can lead to hypercalcemia."
For latent tuberculosis testing, he pointed out that the IFN-gamma release assay (IGRA) is thought to be more accurate than the TST. "IGRA significantly reduces false-positive results" in bacille Calmette-Guérin–vaccinated patients, said Dr. Rosenbach, who is also director of the cutaneous sarcoidosis clinic at the University of Pennsylvania. "Cost-benefit analyses suggest that IGRA [is] cost equivalent to TST, and the Centers for Disease Control and Prevention recommends that IGRA may be used in all circumstances in which the TST is currently used. However, both TST and IGRA have decreased responsiveness and lower sensitivity in patients with impaired immune systems."
In terms of the impact of sarcoidosis on the thyroid gland, a recent analysis of a large database in the United Kingdom found that hyper- and hypothyroidism were twice as common in patients with sarcoidosis, compared with a control population (Postgrad. Med. J. 2009;85:233-7).
A more recent study of 50 patients with cutaneous sarcoidosis conducted by Dr. Rosenbach and his colleagues found that 25% of patients had abnormal thyroid laboratory test results (J. Am. Acad. Dermatol. 2012;66:167-8).
The precise association between sarcoidosis and malignancy remains unclear, he said, but the best available studies suggest that the incidence of lymphoproliferative disorder may be increased in patients with sarcoidosis. Other granulomatous dermatitides may be associated with hematologic abnormalities. Authors of one review found that granulomatous dermatitides may be the first sign of underlying myelodysplastic syndrome (MDS), and recommended that clinicians consider looking for underlying MDS in patients with unexplained or atypical granulomatous skin eruptions (Arch. Dermatol. 2011;147:331-5).
Images courtesy Dr. Misha Rosenbach
A sarcoidosis case on a patient’s nose.
A common stepwise approach for treating patients, Dr. Rosenbach said, begins with skin-directed therapies in the form of steroids or injections. The second step involves the use of antimalarials and tetracycline-class antibiotics; the third step involves methotrexate and/or prednisone, and the fourth step involves consideration for treatment with infliximab or adalimumab. "At this point, etanercept should probably not be used," Dr. Rosenbach said. "It appears to be less effective, and in a few reports has been associated with worsening of disease."
The data are strongest for infliximab, he said, at a recommended dosage of 5 mg/kg at 0, 2, and 6 weeks, and then with maintenance therapy every 6-8 weeks. Adalimumab appeared to work best at 40 mg every week, he said, "but the addition of low-dose methotrexate is sometimes necessary to either regimen."
Dr. Rosenbach disclosed that he was an investigator for a clinical trial sponsored by Centocor and Johnson & Johnson to investigate biologics for chronic/refractory sarcoidosis.