December 2005

Fig.3

Post Infliximab (Remicade) therapy

Fig.

Fig.5

DIAGNOSIS: Cutaneous Sarcoidosis
See July/August 2001 Case of the Month

HISTOPATHOLOGY: Multiple dermal non-caseating granulomas in the superficial and mid-dermis (Fig.3).

LABORATORY FINDINGS: Renal function, liver function, complete blood count, and calcium levels were normal. Chest X-ray revealed small, bilateral calcified nodules within the mediastinum and hila. Ophthalmologic findings included early signs of cataracts, but no uveitis. Serum angiotensin-converting enzyme (ACE) level was 79 U/L (normal 10-55 U/L).

COURSE:
The patient had been given multiple short-term courses (i.e. 3-4 weeks) of prednisone, which did provide temporary relief of her rash and myalgias. Long-term corticosteroid therapy was limited by dramatic weight gain, cataracts, and potential for other toxicities.
Multiple steroid-sparing agents were attempted, but discontinued due either to lack of efficacy, toxicity, or both: minocycline (hyperpigmentation), chloroquine (leukopenia), thalidomide (dyspnea), methotrexate (leukopenia), and allopurinol (lack of efficacy). Topical glucocorticosteroids and topical tacrolimus were also tried, but neither was efficacious as monotherapy.
Intravenous infliximab (Remicade®) was administered at a dose of 5 mg/kg at weeks 0, 2, and 6. A negative PPD was obtained at baseline prior to infliximab therapy. Our patient noted significant improvement in both her cutaneous symptoms (soreness, itching) and muscle aches after 2 weeks of intravenous infliximab. She had experienced 90% clearance by week 6 (Figs.4,5). The patient did not experience any adverse effects during therapy.
The patient's therapy was discontinued given difficulties to obtain continued insurance coverage for infliximab. She was then started on adalimumab (Humira®) SQ 40 mg weekly, and had a similar therapeutic benefit for 6 months, before therapy was discontinued due to a lack of continued insurance coverage.
The patient has most recently been maintained successfully on mycophenolate mofetil (CellCept®) at 1.5 g twice daily.

DISCUSSION
Sarcoidosis is a multi-system disease affecting the lungs, eyes, lymph nodes, skin, gastrointestinal tract, heart, musculoskeletal system, kidneys, and central nervous system. Cutaneous involvement occurs in approximately 25% of patients with sarcoidosis, with lesion morphologies varying widely. Lupus pernio, violaceous papules and plaques, subcutaneous nodules, ichthyosis, alopecia, and verrucous growths may each occur.
It is hypothesized that persistent exposure to a specific, low potency antigen catalyzes the proinflammatory cascade seen in sarcoidosis. The classic noncaseating granulomatous infiltration seen with sarcoidosis is composed primarily of macrophages and CD4+ helper T-lymphocytes. These cells secrete proinflammatory cytokines, such as interleukin-12 (IL-12), interferon gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-_), which direct naïve T-lymphocytes to differentiate into activated Th-1 cells. Therefore, sarcoidosis is maintained by a dominant, polarized Th-1 immune response.
Current treatment options for sarcoidosis focus on inhibition of the proinflammatory cytokines that maintain this response, but are frequently limited in clinical practice due to adverse effects. Oral glucocorticoids, antimalarials, methotrexate, thalidomide, minocycline, allopurinol, and phototherapy are all viable treatment options. Mycophenolate mofetil has a favorable toxicity profile and has been reported to have success in the treatment of cutaneous sarcoidosis. Anti-TNF-_ biologic agents, specifically infliximab and adalimumab, have also been reported to work with considerable success. Such newer agents offer promise, but larger investigations are necessary to confirm their place in our therapeutic armamentarium.

REFERENCES:
1. Moller DR. Treatment of sarcoidosis ­ from a basic science point of view. J Intern Med. 2003;253:31-40.

2. Sharma OP. Sarcoidosis of the skin. In: Freedberg IM, Eisen AZ, editors. Fitzpatrick's Dermatology in General Medicine. Fifth Edition. New York: McGraw-Hill; 1999:2099-2106.

3. Mallbris L, Ljungberg A, Hedblad MA, Larsson P, Stahle-Backdahl M. Progressive cutaneous sarcoidosis responding to anti-tumor necrosis factor-alpha therapy. J Am Acad Dermatol. 2003;48:290-293.

4. Haley H, Cantrell W, Smith K. Infliximab therapy for sarcoidosis (lupus pernio). Br J Dermatol. 2004;150(1):146-9.

5. Heffernan MP, Anadkat MJ. Recalcitrant Cutaneous Sarcoidosis Responding to Infliximab. Arch Dermatol. 2005; 141: 910-911.

This case was presented by Milan Anadkat, MD and Michael Heffernan, MD.