High local interleukin 5 production in granuloma faciale (eosinophilicum): role of clonally expanded skin-specific CD4+ cells

Abstract

that GPs find it difficult to recognize skin cancer and prioritize referrals. Limited urgent capacity is filled with routine referrals at the expense of delaying detection of skin cancer from nonurgent referrals. Dermatologists must therefore pay particular attention to nonurgent referrals to ensure that these referrals are assigned equal priority.In summary, skin cancers are referred urgently and nonurgently by GPs. The urgency assigned to the referral influences the waiting time. Administrative streamlining helps to meet the 2-week target for urgent referrals but further resources are needed so that nonurgent referrals can be seen more quickly. SIR, Granuloma faciale (eosinophilicum) is a rare granulomatous inflammation of the skin usually presenting as infiltrated multiloculated reddish nodes of the face, although there have been several reports of similar lesions in extrafacial localizations. 1-3 The aetiopathogenesis of this condition is not clear, and several hypotheses including cutaneous vasculitis have been proposed. 4 A histological hallmark of the disease is the infiltration of numerous eosinophilic granulocytes together with macrophages and lymphocytes in a typical granulomatous pattern. 5 We have analysed the cellular infiltrate and cytokine production in two patients presenting with granuloma faciale (eosinophilicum).Patient 1 was a 44-year-old white man who described slowly progressive dark red papules and plaques arising at the cheeks and ear lobes for at least 10 years (Fig. 1A). He had undergone several treatments including local steroid injections, cryosurgery and dapsone before being transferred to our department. After informed consent was obtained, a biopsy was taken from an untreated newly developing lesion at his left ear lobe.Patient 2 was a 67-year-old white woman who presented with a 5-year history of continuously growing firm red plaques at both cheeks and the forehead. The skin lesions were painless and had inconstantly increased in size. At initial presentation we saw multiple painless red nodules of 1-2 cm diameter with a tender consistency located at the forehead and both cheeks (Fig. 1E). After informed consent was obtained, two biopsies were taken from different skin lesions and were split for (immuno)histology and molecular biology.Routine haematoxylin and eosin staining in both patients showed subcutaneous granuloma formation with multinucleated giant cells surrounded by lymphocytes and a prominent infiltration of granulocytes among which eosinophils clearly dominated (Fig. 1B,F). The histological picture and the clinical appearance were consistent with facial granuloma.Immunohistochemistry showed a dominant recruitment of CD4+ T cells among the infiltrating lymphocytes (Fig. 1C,G) and only a weak staining for CD8 (data not shown), a result which confirmed previous investigations 6 (all antibodies from Dako, Hamburg, Germany).We next searched for an explanation for the parallel infiltration of CD4+ T cells and the infiltration of numerous eosinophils into the skin. A major cyto...

Granuloma faciale with extrafacial involvement and response to tacrolimus

“…[10] In addition, an increased production of IL-5, probably induced by the clonal expansion of a locally recruited T-cell population may enhance the attraction of eosinophils into the lesions of GF. [11] Therefore, a possible mechanism of action of topical tacrolimus in this condition may be the inhibition of IFN-gamma and IL-5 production and release, induced by the down-regulation of the T-cell activity, primarily involving the calcineurin binding and inactivation. However, we did observe eosinophils in skin biopsy in our case, probably since the biopsy was taken after one year of oral dapsone.…”

Successful Treatment of Granuloma Faciale with Topical Tacrolimus: A Case Report and Immunohistochemical Study

“…Interestingly, a previous report also suggested that topical administration of tacrolimus ointment increased the number of IL-10 producing cells and enhanced the production of TGF-β [11]. Regarding GF, Gauger et al [12] previously reported that increased levels of IL-5 in the lesional skin might contribute to the pathogenesis of GF. In our present case, indeed, the eruption diminished after 2 months of topical administration of 0.1% tacrolimus.…”

Eosinophilia in Dermatologic Disorders

“…58 A local IL-5 production by T cells most likely contributes to eosinophil infiltration. 59 Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)…”