Lupus erythematosus panniculitis treated with tacrolimus

ARTICLE

ejd.2012.1650

Auteur(s) : Takashi Ueda¹ ueder@med.kitasato-u.ac.jp, Hiromitsu Eto¹, Kensei Katsuoka¹, Yasuo Takeuchi²

¹ Department of Dermatology,

² Department of Nephrology, Kitasato University School of Medicine, 1-15-1 Kitasato Minami-ku, Sagamihara Kanagawa 252-0375, Japan

Lupus erythematosus panniculitis (LEP) is a rare manifestation of lupus erythematosus, which sometimes appears before or after the onset of cutaneous or systemic lupus erythematosus [1]. LEP typically manifests as indurated nodules and erythema, which may show scaling, follicular plugging, atrophy, dyspigmentation, telangiectasia or ulceration. The panniculitis often resolves leaving depressed, atrophic scars and often recurs.

A 39-year-old Japanese man presented with a 2-month history of erythema and indurated nodules on the right upper arm on a background of systemic lupus erythematosus and lupus nephritis treated with systemic corticosteroids since 2005. The cutaneous symptoms appeared in October 2009, and the erythema gradually enlarged with atrophy, telangiectasia and ulceration (figure 1A). At that time, he was on prednisolone (PSL) at 10 mg/day. There was evidence of an aggravation of his lupus nephritis; his laboratory data showed urine protein of 3+ (urine total protein/creatinine ratio (TP/Cre) was 2.64) with hypoproteinemia (albumin 3.2 g/dL). The platelet count was 10.4 cells/μL. The level of C3 was 53 mg/dL, C4 7 mg/dL and CH50 was 22 U/mL. Other laboratory parameters including serum biochemistry, liver function tests and renal function were within normal limits. Antinuclear antibody titer was greater than 1:40 with a speckled type and antibodies to double-stranded DNA and Sm were negative. A skin biopsy taken from the erythema showed an inflammatory infiltrate around dermal vessels and eccrine coils consisting of lymphocytes, plasma cells, macrophages and foam cells with nuclear fragments. There was fat necrosis with fibrin deposition and hyalinization of adipose lobules (figure 1D, E).

A diagnosis of LEP was made based on the clinical presentation and histology. The PSL was increased to 30 mg/day with the addition of alprostadil (60 μg/day), and the ulcer underwent debridement and topical treatment. However, the lupus nephritis and erythema were unresponsive to treatment with rapid enlargement of the ulcer (figure 1B). In February 2010, tacrolimus was commenced at 3 mg/day for the treatment of the lupus nephritis in addition to the corticosteroids. The erythema reduced after 1 month and both the erythema and ulceration almost completely resolved after 4 months, leaving an atrophic scar (figure 1C). Moreover, the TP/Cre decreased to 0.69 and the hypoproteinemia (albumin 3.9 g/dL) resolved after 4 months. We tapered the dose of PSL to 14 mg/day and tacrolimus to 3 mg/day and there has been no recurrence of the LEP for almost 2 years.

Previous reports showed that the lymphocytes infiltrating the panniculitis lesions were predominantly T helper cells, which may interact with B cells and macrophages. However, the pathogenesis of LEP as well as the mechanism leading to skin ulceration is unknown. Skin ulceration has been reported in approximately 7% [2] and 28% [3] of patients with LEP in past reports.

LEP is usually managed with antimalarials (hydroxychloroquine) and thalidomide is sometimes used. As they are not available in Japan for LEP, diaminodiphenylsulfone has been used mostly in Japan [4]. Other therapies include oral corticosteroids and immunosuppressive agents such as azathioprine, cyclophosphamide, mycophenolate mofetil and cyclosporine.

Although tacrolimus and cyclosporine are both calcineurin inhibitors, to the best of our knowledge, tacrolimus has not been used to treat LEP. Tacrolimus ointment in patients with various forms of cutaneous lupus erythematosus without LEP is known to be effective [5]. In the present case, tacrolimus was effective and safe for maintenance treatment of lupus nephritis. Tacrolimus is a calcineurin inhibitor and macrolide isolated from Streptomyces tsukubaensis. Tacrolimus selectively inhibits the transcription of interleukin-2, interleukin-10 and several other cytokines, mainly in T cells. It does not target B cells directly but works indirectly by interfering with T cell help [6].

Disclosure

Financial support: none. Conflict of interest: none.

References

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