Treatment of refractory adult-onset pityriasis rubra pilaris with TNF-alpha antagonists: a case series.

BACKGROUND: Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long-term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long-term follow-up or comparison between different biological agents. OBJECTIVES: To assess the long-term efficacy and safety of TNF-alpha antagonist, infliximab and etanercept, either in monotherapy or in combination therapy of severe, refractory adult-onset PRP. METHODS: Seven patients of adult-onset PRP, six newly diagnosed type-I and 1 type-II, which were resistant or ineligible to conventional systemic treatment, received a single course of infliximab or etanercept therapy, alone or in combination with low-dose acitretin (>0.25 mg/kg/daily). After complete remission and treatment discontinuation, a follow-up period of 12 months was evaluated for relapses. RESULTS: Six patients obtained complete remission after a single course of anti-TNF-alpha therapy: mean therapy duration was 19.3 weeks (range 6-48 weeks). All patients obtained significant clearing (>75% of body surface area) of skin lesions at week 12. Two patients with marked keratoderma developed localized disease recurrence during treatment. During follow-up, only a single patient, affected by type II PRP, had disease relapse. CONCLUSIONS: Both TNF-alpha antagonists proved successful for the treatment of refractory, adult-onset PRP, yielding complete and persistent clinical responses in type-I PRP. Infliximab was associated with a more rapid onset of action, while treatment duration was comparable with etanercept. PRP type II warranted long-term therapy and showed relapse after drug discontinuation.

Factor VIII complex in progressive systemic sclerosis.

Factor VIII complex and its related activities (Coagulant, Antigen and Ristocetin Cofactor) have been investigated in 23 patients with Progressive Systemic Sclerosis (PSS) divided into two groups: acrosclerosis and diffuse sclerosis. All Factor VIII-related activities were higher in PSS patients than in normal subjects. No difference in F. VIII-related Antigen (F. VIIIR:Ag), F. VIII-related Ristocetin Cofactor (F. VIIIR:Co) and F. VIII Coagulant activity (F. VIII:C) was found comparing the patient groups. F. VIII:C was increased significantly less than F. VIIIR:Ag and F. VIIIR:Co in both patient groups. Some hypotheses about the pathogenesis of this increase are discussed.

An evaluation of some inflammatory, coagulative and immune factors in progressive systemic sclerosis.

Thirty-five patients affected by Progressive System Sclerosis (PSS) (20 acrosclerosis and 15 diffuse sclerosis) were subjected to the following laboratory tests: Beta 2 microglobulin (B2m), Fibronectin, C3c, C4, Fibrinogen, Factor VIII Coagulant (F. VIII:C), Factor VIII related Antigen (F. VIII:Ag), IgG, ESR, Antithrombin III (AT III), alpha 1 Antitrypsin (alpha 1AT) and alpha 2 Macroglobulin (alpha 2M). The results showed that no difference was observed between the normal group and the groups of PSS patients with respect to alpha 1AT, alpha 2M, and AT III. In contrast the B2m, ESR, IgG, F. VIII:Ag results were significantly higher in the PSS patients, while Fibrinogen and C3c results were slightly higher, but no high enough to be of statistical significance. The two PSS patient subgroups did not produce significant results, only the C4 values were lower in the Diffuse Sclerosis subgroup. From these results it seem that the tests used are not very useful indifferentiating the two subgroups of the PSS patients.

Two cases of toxic epidermal necrolysis caused by delayed hypersensitivity to beta-lactam antibiotics.

The authors describe two cases of toxic epidermal necrolysis (TEN) caused by delayed hypersensitivity to semisynthetic penicillins. The first patient developed erythema of the lower limbs following an i.m. injection of ampicillin, which progressed to TEN as therapy was continued. Fever and eosinophilic leukocytosis were also present. In the second case, TEN developed following oral amoxicillin therapy, and was preceded by a diffuse, maculopapular eruption. In both cases, symptoms resolved with the prompt administration of steroids. Both patients underwent allergological testing: prick test and, if results were negative, intradermal tests with penicilloyl-polylysine (PPL), minor determinant mixture (MDM), penicillin, amoxicillin and ampicillin. Patch testing with penicillin, ampicillin and amoxicillin was also performed. Both patients developed positive reactions to the intradermal tests after 6 h, and to patch tests after 48-72 h (for ampicillin, amoxicillin and penicillin in the first case, and for ampicillin and amoxicillin in the second). The lymphocyte transformation test (LTT), performed only in the first case, was positive for ampicillin. As these cases demonstrate, delayed hypersensitivity should be suspected in cases of drug-related TEN. Patch testing is a simple and useful allergological test for these types of cases.

Serum beta 2-microglobulin in systemic sclerosis.

The role of beta 2 microglobulin (beta 2-m) in Systemic Sclerosis (SS) has been evaluated. Twenty-four female patients have been examined: 15 of them were affected by acrosclerosis (Group 1) and 9 of them by diffuse sclerosis (Group 2). 46.6% of Group 1 and 44.4% of Group 2 had values significantly higher than normal controls. (P less than 0.01 and P less than 0.005 respectively). The authors deal with the validity of the use of B2-m as index of inflammatory activity of the disease.

Vasculitic purpura in vinyl chloride disease: a case report.

Vinyl chloride (VC), a volatile substance mostly used for polyvinyl chloride (PVC) synthesis, is a systemic toxicant particularly noxious to endothelium. Angiosarcoma of the liver, Raynaud's phenomenon, scleroderma-like lesions, acroosteolysis and neuritis are known to be typical vinyl chloride-associated manifestations (VC disease). A so far unknown feature of the disease is purpura. This was first observed by the authors in a worker of a PVC-producing plant. The skin eruption was characterized by small purpuric maculae with tiny, palpable spots and papulae, mostly concentrated on the lower part of the legs, changing into bullae, pustules and crusts and tending to spontaneous regression after withdrawal from VC exposure. A skin biopsy revealed marked inflammatory reaction with a mostly lymphocytic and histiocytic infiltration around and in the walls of dermal arterioles. The finding of increased circulating immune complexes and anti-smooth muscle autoantibodies strengthens the hypothesis that immunologic changes play a role in the appearance of "vinylic purpura."

[Ultrastructural observations on amastigote forms of Leishmania donovani in a case of laryngeal leishmaniasis]. / Osservazioni ultrastrutturali sull'amastigote di Leishmania donovani in un caso di leishmaniosi laringea

An ultrastructural study on the amastigote stage of Leishmania donovani, in a rare case of laringeal involvement, was carried out. Many details of the fine morphology of this protozoon were observed under the electron microscope, i.e.: the outer membrane of host origin, periplast, subpellicular microtubules, kinetoplast, flagellum, flagellar pocket, multivesicular bodies. A presence of a new organelle (4 microtubules structure close to and running parallel to the flagellar pocket), previously not described in Leishmania donovani's species, was demonstrated in this indigenous strain (from Central Italy). The Authors found a limited number of subpellicular microtubules in this strain, i.e.: 72 microtubules. Differences in size and number of microtubules between strains must be investigated in more rigorous morphometric studies. It's possible that the number of the subpellicular microtubules represents a new taxonomic character.

[Ophthalmoplegia in dermatomyositis]. / Oftalmoplegia in dermatomiosite

A case in which apparently myasthenic ophthalmoplegia had been observed more than six years prior to the onset of dermatomyositis is reported. The clinical picture is described and the possibility of a partially common pathogenesis for both forms is mooted. It is suggested that initial local disturbance of neuromuscular transmission was eventually followed by "aggression" against the muscle fibres.

[The blood coagulation system in progressive systemic scleroderma]. / Il sistema emocoagulativo nella sclerodermia sistemica progressiva.

Twenty-five scleroderma patients have been studied to evaluate blood coagulative and fibrinolytic parameters. An increase in FVIII related activities and a reduction in fibrinolytic activity was observed. These changes may be related to the endothelial damage present scleroderma patients I the consequent "in loco" activation of blood coagulation may cause the microthrombosis that is very often observed in the earliest phases of the disease.

[Presence of clusters of Langerhans cells and lymphoid cells in the peritumoral infiltrate of a case of basal cell naevus syndrome. Ultrastructural study (author's transl)]. / Sur la présence d'agrégats constitués de cellules de Langerhans et cellules lymphoïdes dans l'infiltrat péri-tumoral dans un cas de naevomatose baso-cellulaire. Etude ultrastructurale.

A case of naevoid basal cell carcinoma syndrome with clusters of Langerhans' and lymphoid cells in the inflammatory peritumoral infiltrate, is reported. Electron microscopy shows intercellular contacts between eight to ten lymphoid cells and a single Langerhans' cell. These contacts occur over limited areas of the cell membranes by means of zones of high electron density on the outer edge of the cytoplasm. The functional significance of this finding is discussed, bearing in mind that recent observations have established certain analogies between Langerhans' and interdigitating reticulum cells. The latter might, within the thymus-dependent region of the lymph nodes, contribute to the formation of a micro-environment favourable to certain immunological activities of T-lymphocyte populations.