Case Report: Autoimmune Pemphigus Vulgaris in a Patient Treated With Cemiplimab for Multiple Locally Advanced Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Pemphigus vulgaris (PV) is a rare and severe autoimmune blistering disorder affecting the skin and mucous membranes, characterized by the production of autoantibodies against two desmosomal adhesion proteins, desmoglein 1 and 3. In patients with advanced squamous cell carcinoma of the skin unfit for surgery and radiotherapy, immune check-point inhibitors, including the anti-Programmed Death-1 (PD-1) agent cemiplimab have been successfully employed proving relevant clinical outcomes. Cemiplimab is a monoclonal antibody capable of inhibiting PD-1 signalling that has recently been approved for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinoma. Although the peculiar setting of advanced CSCC involving elderly patients, rare and unusual skin immune-related adverse events such as PV could be observed in cemiplimab treated patients. CASE REPORT: A 95-year-old man without a history of autoimmune disease was treated with cemiplimab for multiple and advanced squamous cell carcinomas of the head obtaining a complete response to therapy. After seven cycles of cemiplimab administered every 21 days, the patient developed a mucocutaneous blistering eruption. Clinical diagnosis of PV was suspected on the basis of the diffuse involvement of trunk and extremities with large blisters and necrotic eschar. It was carried out an ELISA test, that showed high level of circulating antibodies against desmoglein 1, thus confirming the diagnosis of PV. For this reason, cemiplimab infusion was discontinued and complete resolution of skin lesions was obtained using oral prednisone 0,8 mg/kg/daily for four weeks. Once remission was achieved, a maintenance dose of 10 mg/day was administered, observing a good control of bullous disease and low value of desmoglein 1. Response to CSCC persisted also during cemiplimab discontinuation, until obtaining a complete remission still persisting at 9 months after the last cycle of therapy. CONCLUSION: The case we observed is the first description of PV revealed from cemiplimab therapy, thus suggesting that cemiplimab could allow the arise of underlying autoimmune PV, through a mechanism both T and B-cell-mediated.

Therapeutic hotline: Re-induction may be useful to manage psoriasis relapse during long-term maintenance treatment with infliximab: a retrospective analysis.

Infliximab is an anti-tumor necrosis factor-alpha monoclonal antibody that is highly effective for the treatment of psoriatic disease. During maintenance treatment, some patients may experience a disease relapse, and, in such circumstances, dose intensification is frequently used to regain efficacy. We report our cumulative experience on the use of infliximab re-induction in patients whose psoriasis relapsed during long-term maintenance treatment with infliximab. From September 2005 to January 2009, 22 patients required re-induction because of a relapse of their psoriasis. Re-induction was effective in restoring response in most patients and was well tolerated in all cases, without occurrence of serious or unexpected adverse events.

An overview of delayed pressure urticaria with special emphasis on pathogenesis and treatment.

Delayed pressure urticaria (DPU) is a physical urticaria characterized by the development of deep swellings at sites of pressure application on the skin. Etiopathogenesis of DPU is still unknown, although the available evidence suggests the involvement of mast cells through non-immunologic mechanisms and the role of several mediators beyond histamine, such as proinflammatory cytokines. The management of DPU is complex, also considering that prevention is very difficult and DPU frequently coexists with chronic "idiopathic" urticaria. Moreover, H1-antihistamines, which are the mainstay of treatment for common urticaria, usually provide less satisfactory results as compared with other urticarias. Therefore, numerous treatment alternatives have been proposed for severe refractory cases, such as oral or topical corticosteroids and various drugs with anti-inflammatory effects.

Anti-NuMA antibodies in a psoriatic patient: considerations about clinical relevance and effect of infliximab treatment.

Antibodies against the nuclear mitotic spindle apparatus protein (NuMA) are infrequently detected during antinuclear antibodies testing on HEp-2 cells. In a series of 428 psoriatic patients anti-NuMA antibodies were found only in a patient, at a titer of 1:640, without any apparent clinical relevance. The significance of anti-NuMA is not yet known and is briefly reviewed, also in consideration of potential therapeutic implications. Although biologic drugs targeting tumor necrosis factor-alpha have been associated with the development of non-organ specific autoantibodies and rare reports of autoimmune phenomena, infliximab was well tolerated in this patient and caused no changes in autoantibody titers.

Cutaneous lupus erythematosus: clinico-pathologic correlation.

Cutaneous lupus erythematosus (CLE) is a chronic-relapsing disease. It is defined as a LE localized to the skin without any significant systemic symptoms. Its annual incidence is of 4 cases per 100,000 persons with a prevalence of 73 cases per 100,000 persons. The etiology is unknown but it is considered as a prototype of autoimmune disease in which genetic factors (HLA), environmental factors (photo exposure and cigarette smoking) and pharmacological agents play an important role. The most accepted classification includes three clinical variants: acute (ACLE), subacute (SCLE) and chronic (CCLE). A fourth variety is the intermittent form (ICLE) also called "lupus tumidus" (LET) which is considered by some authors a distinct form from CCLE. The skin lesions are subdivided into LE specific and LE non-specific. The latter have a considerable importance as a symptom of evolution of the disease towards a systemic form of lupus (SLE). The histopathology of CLE is characterized by an interface dermatitis with vacuolization of the basal layer, a predominantly lymphocytic, perivascular and periadnexal infiltrate, epidermal and follicular hyperkeratosis, deposit of positive PAS material at the dermo-epidermal junction leading to atrophic-cicatricial evolution. Depending on the clinical variants, these microscopic features are more or less evident and are associated with peculiarities such as deposits of mucin (SCLE and LET), involvement of the panniculus in LE panniculitis, disappearance of the adnexa (cicatricial alopecia). The relationship between SLE/CLE is still under study: the progression of CLE in SLE is reported in a variable percentage of cases ranging from 12 to 18%. CLE therapy is aimed at preventing recurrences and scarring outcomes. Photoprotection with clothing, chemical and physical sunscreens active on UVA and UVB radiations is very important. Topical therapy is based on the use of steroids and calcineurin inhibitors, while the systemic therapy includes hydroxychloroquine as the first drug of choice.