[Pansclerotic porphyria cutanea tarda after chronic exposure to organic solvents]. / Pansklerotische Skleroporphyrie nach langjähriger Exposition gegenüber organischen Lösungsmitteln.

A 63 year old man developed generalized scleroderma with massive sclerotic areas, particularly in the abdominal region, four years after being diagnosed with porphyria cutanea tarda (PCT). He had almost daily exposure to organic solvents (benzene, trichlorethylene) for many years. The cutaneous fibrosis progressed dramatically leading to a pansclerosis, even though the uroporphyrin levels were borderline and the liver enzyme values were normal. Organic solvents are among those substances which can cause a cutaneous fibrosis. The unusually complicated clinical development in our patient was a combination of the two initial factors, the PCT and the long term exposure to organic solvents. The pansclerotic PCT was differentiated from a systemic sclerosis, a disabling pansclerotic morphea and a generalized morphea by means of histological examinations, the absence of a Raynaud phenomenon and the non-involvement of additional organs. Auto-antibodies typical for systemic sclerosis were negative. Using a medium dosage of UVA1 phototherapy and intensive physiotherapy, the progression of the skin disease was stopped and the sclerosis improved.

Lower relapse rate of botulinum toxin A therapy for axillary hyperhidrosis by dose increase.

BACKGROUND: Primary focal hyperhidrosis is a common condition that gives rise to functional and emotional problems and may disturb professional and social life. Recently, low-dose intracutaneous injections of botulinum toxin A have been shown to induce a temporary anhidrosis, with relapses occurring usually after 4 to 6 months. OBJECTIVE: To evaluate the short- and long-term effectiveness and possible adverse effects of high-dose botulinum toxin therapy in the treatment of axillary hyperhidrosis. DESIGN: In an open study, patients with focal hyperhidrosis were treated with intracutaneous injections of botulinum toxin A (Botox; Allergan Inc, Irvine, Calif). A total dose of 200 U of botulinum toxin A was used once per axilla. Patients were observed for up to 15 months. SETTINGS: University medical center. PATIENTS: Twenty-four patients with axillary hyperhidrosis were treated. Their ages ranged from 19 to 58 years (mean +/- SD, 34.8 +/- 12.4 years). MAIN OUTCOME MEASURES: Reduction of sweating as assessed by the Minor iodine-starch test and planimetry of hyperhidrotic areas. Patients were interviewed at the end of follow-up about their satisfaction with this treatment. RESULTS: Within 6 days, all patients reported cessation of excessive sweating. The mean +/- SD area of excessive sweating identified by the Minor iodine-starch test decreased from 19.27 +/- 11.95 cm2 to 0.25 +/- 0.61 cm2 (P<.001). The mean follow-up was 10.0 +/- 2.8 months (range, 5-15 months). Four patients (17%) reported a return of axillary hyperhidrosis after 7 to 10 months. All patients who experienced relapse showed an excellent response to a second treatment. The only adverse effects reported were temporary pain and burning during the injections. No muscular weakness, insensitivity, or systemic reactions were observed. CONCLUSIONS: High-dose botulinum toxin A seems to be as safe as low-dose botulinum toxin A in the treatment of axillary hyperhidrosis. The preliminary data suggest a lower rate of relapse.

Mapping of T-cell epitopes of Phl p 5: evidence for crossreacting and non-crossreacting T-cell epitopes within Phl p 5 isoallergens.

BACKGROUND: Group 5 allergens represent major grass pollen allergens because of their high sensitization indices. The identification of T-cell epitopes of these allergens is a prerequisite for the design of immunotherapeutic strategies based on peptide vaccination or modified allergens with conserved T-cell epitopes. OBJECTIVE: This study was undertaken to determine T-cell epitopes on Phl p 5 major pollen allergen of timothy grass (Phleumn pratense). METHODS: T-cell lines (TCLs) and T-cell clones (TCCs), specific to Phl p 5, were established from the peripheral blood of 18 patients allergic to grass pollen. All TCCs were mapped for epitope specificities using 178 overlapping dodecapeptides representing the primary structures of two isoforms of Phl p 5 (Phl p 5a and Phl p 5b). Phenotype and cytokine production profiles of TCCs were tested. Selected TCCs were analysed for HLA class II restriction. RESULTS: A total of 82 TCCs were isolated. All TCCs displayed the helper cell (TH) phenotype. Their reactivity with two recombinant expressed isoforms of Phl p 5a and Phl p 5b was heterogeneous. The epitope specificity of the TCCs was then revealed. Nineteen T-cell epitopes could be identified on Phl p 5. Eighty-one percent of mapped TCCs recognized three T-cell reactive regions on the Phl p 5 allergen. Some TCCs were reactive with isoepitopes presenting on Phl p 5a as well as Phl p 5b. Allergen-specific stimulation induced a TH0-like type of cytokine production in 25 of 50 TCCs. Almost all TCCs secreted high concentrations of interleukin-13. CONCLUSION: Phl p 5, a major grass pollen allergen, contains several T-cell epitopes. Some epitope regions were recognized by several patients. Epitope recognition pattern could not be correlated with special HLA class II haplotypes. T-cell stimulating isoepitopes were found at corresponding regions of Phl p 5a and Phl p 5b isoforms.

Group 5 allergens of timothy grass (Phl p 5) bear cross-reacting T cell epitopes with group 1 allergens of rye grass (Lol p 1).

Selected human T cell clones reactive with group 5 allergens of timothy grass (Phl p 5) were cross-stimulated in specific proliferation assays with group 1 allergens of rye grass (Lol p 1). Such interspecies cross-reactivities result obviously from structural motifs presented on defined Phl p 5 fragments as shown with recombinant Phl p 5 products.

Analysis of human T cell clones reactive with group V grass pollen allergens.

Twenty-seven T cell clones (TCC) reactive with group V allergens of Phleum pratense (Phlp V) were established from the peripheral blood of 3 patients allergic to grass pollen. Twenty-four TCC showed the helper cell phenotype CD3+, CD4+, CD8-; the remaining clones were CD3+CD4-CD8+. T cell recognition of Phlp V was exclusively HLA-DR restricted. Many of the Phlp V reactive TCC (19 of 27; 70%) were stimulated additionally by other group V allergens isolated from Lolium perenne, Poa pratensis, and Dactylis glomerata. These data indicate the existence of cross-reacting T cell epitopes among group V allergens of different grasses. The Phlp V triggered cytokine production demonstrated in 13 out of 24 CD4+ TCC a Th2-like pattern (high interleukin 4/gamma-interferon ratios) suggesting group V allergens as important targets of grass pollen specific IgE.