Could Anakinra Cause Sarcoidosis?
A 55-year-old white woman with rheumatoid arthritis (RA) for more than 10 years developed typical cutaneous sarcoidosis and erythema nodosum. Histologic examination and chest x-ray proved sarcoidosis. Until June 2002, her therapy for RA was corticosteroids in varying doses. Since July 2002, the patient has received anakinra. Could the anakinra have caused sarcoidosis?

Burkhard Bratzke, MD

Transition from well-defined connective tissue disorders such as rheumatoid arthritis and systemic lupus and histologically defined sarcoidosis is well described, as are the reverse "conversions." Whether this represents a clear genetically defined and/or antigenically triggered movement from one disorder to another or is simply a different disease phenotype that evolves in a given patient is unknown. Whichever the direction of disease change, the therapy is usually guided by and responsive to the dominant clinical features.

A noncaseating granuloma is quite a nonspecific pathologic entity and can be seen in many inflammatory, allergic, infectious, and neoplastic disorders. Its formation is dependent on the presence of a specific combination of immune cells and cytokines. Similarly, erythema nodosum is quite a nonspecific histologic (septal panniculitis) and clinical finding and can be seen in the setting of or activated by infections such as tuberculosis and streptococci, drug reactions to oral contraceptives and sulfa drugs, inflammatory bowel disease, and neoplasms. At times, an erythema nodosum lesion due to various (nonsarcoid) causes can show noncaseating granulomatous changes. When it is seen in the context of a periarthritis about the ankles and hilar adenopathy, it is called Lofgren's syndrome, a benign form of sarcoid that is quite sensitive to a short course of low-dose steroids. The diagnosis of sarcoidosis is dependent on the finding of such a granuloma and the ruling out of the above-mentioned disorders on clinical, laboratory, radiologic, and pathologic grounds.

Anakinra is a recombinant human interleukin-1 (IL-1) receptor antagonist that has been approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis, a disorder with inflammatory and tissue-damage features mediated by the cytokine IL-1. The fact is that the body is a finely tuned organism that, in health, is kept in equilibrium by a careful balance between pro- and anti-inflammatory chemicals. A drug-related "shift in the force" and balance of these cytokines could lead to a new immunologic set point and new clinical features. Tumor necrosis factor alpha blockers have been quite effective in RA but rare cases of drug-induced systemic lupus erythematosus have been reported in patients who had initially had RA for many years. Also, various drugs can lead to erythema nodosum without hilar adenopathy.

Thus, it is likely that the anakinra did play a role in the "switch" from RA to sarcoidosis and should be avoided.