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Describes a patient with a subcorneal pustular dermatosis (SPD) type of immunoglobulin A (IgA) pemphigus. Presentation of an associated IgA paraprotein; Subcorneal pustules containing neutrophils with few acantholytic cells; Treatment of the patient with dapsone.

Abstract Ofuji papuloerythrodema is a rare type of dermatosis marked by an erythrodermic manifestation which is intensely pruritic and results from the coalescing of brownish papules which in the main do not involve the great folds. The authors present the case history of a 72-year-old female, whose dermatosis appeared 8 years after the diagnosis of malignant lymphocitic lymphoma. The Authors describe the clinical and histopathological picture, illustrating the laboratory results and stressing the importance of the association of the two pathologies in a possible nosological overview. [ABSTRACT FROM AUTHOR]

Background: Digital mucous cysts (DMCs) are benign, translucent, fluid-filled asymptomatic, slow-growing, dome-shaped nodules overlying a joint or tendon sheath on the distal dorsal side of the fingers or, more rarely, on the toes. They are degenerative in nature and are often associated with interphalangeal joint arthritis. Although DMCs are usually solitary, multiple cysts have been observed to develop simultaneously. They can sometimes be painful, confer a reduction in motility, and cause weakness and deformity in the nails. Spontaneous regression is rare, and intervention using surgical or non-surgical treatment is advisable., Methods: We analyzed 53 DMCs of 51 patients treated in two Italian Dermatology Units between January 2004 and March 2015. The aim of this study was to evaluate the most salient clinical, histopathological and dermoscopic features, in addition to the response to treatment. We then compared the data to assess whether the histological type (ganglion-type or focal dermal mucinosis-type) or immunohistochemical phenotype of DMCs is correlated with the likelihood of relapse. All the patients have been treated with simple surgical excision with a cure rate of 72.6% at a mean recurrence time of 160 days with a mean follow-up of 3.6 years., Results: Histopathological examination, performed in 11 out of the 53 cysts, revealed 7 cases of ganglion-type cysts and 4 cases of focal cutaneous mucinosis-type cysts. No correlation was detected between histopathological type and recurrence., Conclusions: Digital dermoscopy confirmed the pattern recently reported in the literature, providing confidence in the clinical diagnosis and reducing the need for preoperative radiography or ultrasound imaging.

Werner syndrome (WS; MIM#277700) or adult progeria, is a rare disease, associated with mutations of a single gene (RECQL2 or WRN), located on chromosome 8 (8p12). It codes a DNA-helicase, whose defects cause genomic instability. The highest incidences are reported in Japan and Sardinia (Italy). On this major island of the Mediterranean Basin, the WS cases have been observed in the northern areas. The authors describe the apparently first case reported in southern Sardinia, a 51-year-old woman, who was born in and resides in the province of Cagliari. She presented with a 9-year history of an intractable leg ulcer and other characteristic symptoms, including "bird-like" face, high-pitched voice, premature greying, short stature, abdominal obesity in contrast with thin body type, scleroderma-like legs, decreased muscle mass, diabetes, atherosclerosis, and premature menopause. A specialized genetic Institute of Research (IRCCS-IDI, Rome) confirmed the clinical diagnosis. There is no cure or specific treatment and patients must be periodically screened for an increased risk of cardiovascular and cerebrovascular disease and malignancies. Among the many findings, leg ulcers significantly affect the patient's quality of life. This problem may send the patient to the dermatologist, who finally suspects the diagnosis. Poor response to medical treatment may require aggressive repeated surgery, with poor or temporary results.

Mutational analysis of the c-kit gene in a patient with a previously undescribed variant of mast cell disease revealed a germline mutation, Phe522Cys, within the transmembrane portion of the Kit receptor protein. Transfection experiments revealed that the mutation caused ligand-independent autophosphorylation of Kit, which was inhibited by the tyrosine kinase inhibitor imatinib mesylate. The patient's bone marrow biopsy and aspirate displayed unique pathologic features with the presence of excessive numbers of mature-appearing mast cells and absence of aberrant mast cell surface expression of CD2, CD25, and CD35. Therapy with imatinib mesylate resulted in a dramatic improvement in mast cell burden and clinical symptoms. These results highlight the significance of the transmembrane region of Kit in activation of the molecule and its importance in mast cell development and suggest a role for screening for transmembrane c-kit mutations in patients with mastocytosis in association with the decision to use imatinib mesylate.

Mutations in the proto-oncogene c-kit cause constitutive kinase activity of its product, KIT protein, and are associated with human mastocytosis and gastrointestinal stromal tumors (GISTs). Although currently available tyrosine kinase inhibitors are effective in the treatment of GISTs, there has been limited success in the treatment of mastocytosis. 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinoid ansamycin antibiotic, which binds to heat shock protein 90 (hsp90) causes destabilization of various hsp90-dependent kinases important in oncogenesis. Treatment with 17-AAG of the mast cell line HMC-1.2, harboring the Asp816Val and Val560Gly KIT mutations, and the cell line HMC-1.1, harboring a single Val560Gly mutation, causes both the level and activity of KIT and downstream signaling molecules AKT and STAT3 to be down-regulated following drug exposure. These data were validated using Cos-7 cells transfected with wild-type and mutated KIT. 17-AAG promotes cell death of both HMC mast cell lines. In addition, neoplastic mast cells isolated from patients with mastocytosis, incubated with 17-AAG ex vivo, are selectively sensitive to the drug compared to the mononuclear fraction. These data provide compelling evidence that 17-AAG may be effective in the treatment of c-kit-related diseases including mastocytosis, GISTs, mast cell leukemia, subtypes of acute myelogenous leukemia, and testicular cancer.

We report a series of 9 patients, 6 men and 3 women, who presented nail hyperpigmentation arising between 6 and 24 months from the start of hydroxyurea therapy. The most commonly observed clinical pattern was that of longitudinal melanonychia. In only 1 patient, who was affected in all 20 nails, we observed longitudinal melanonychia, diffuse melanonychia, and hyperpigmentation of the skin.

A method to perform site-directed random mutagenesis directly in the yeast chromosomal DNA at the iso-1-cytochrome c-encoding gene locus (CYC1) is described. To test the effectiveness of the random mutagenesis procedure, the heme ligand His18 was mutated to Ala (H18A), rendering cytochrome c (Cyc) nonfunctional. Random mutagenesis was performed by transforming yeast cells with a synthetic oligodeoxyribonucleotide (oligo) that randomizes the codon for His18. The transformed cells were then selected for reversion to a functional Cyc on selective media. Ten functional mutants were recovered, all of which had integrated the synthetic oligo. Sequencing showed that five of the recovered mutants carried the His codon, CAU, and five mutants contained the His codon, CAC. Because Arg had previously been found as a heme ligand, this mutant was produced by standard techniques and integrated into the yeast chromosome. These yeast did not produce a holo cytochrome c that was detectable by low-temperature spectroscopy. To develop a selection for nonfunctional Cyc, competent yeast (which lack the ability to synthesize tryptophan) were cotransformed with a plasmid carrying the TRP1 gene and the random oligo, and were plated on media lacking tryptophan. Of the 1200 colonies that grew, 120 tested negative for the integration of the random oligo, demonstrating that this particular selection for nonfunctional protein is not feasible. A method is thus described for directed, random mutagenesis directly in the yeast chromosome that can be used to probe structure/function relationships in Cyc. Only His can act as a heme ligand at position 18, using the functional selection described here.

In order to evaluate whether lymphokine (LK) release is impaired in patients with lepromatous leprosy (LL), the production of two LKs, namely leukocyte inhibitory factor (LIF) and interleukin-2 (IL-2) from peripheral blood mononuclear cells of LL individuals was investigated. Results show that in eight patients CD4+ cells exhibit a reduced release of LIF, while CD8+ lymphocytes are still able to secrete this LK. In the remaining three patients both CD4+ and CD8+ cells produced LIF as do normal lymphocyte subpopulations. As far as IL-2 release is concerned, all patients fail to produce the above LK either using purified CD4+ or CD8+ lymphocytes. These data emphasize additional defects in immune responsiveness in leprosy.

Twenty three patients with lepromatous leprosy (LL) not in reactional phase and bacteriologically negative were evaluated for their immune status (T cell frequency and interferon gamma production). In six patients with deficits of both immune parameters, a synthetic thymic extract (TP-5) was administered. At the end of the treatment, a full recovery of immune dysfunction was observed. In the light of these results, the efficacy of TP-5 as an immunomodulating agent in LL patients is discussed.