[EVALUATION OF DRUG ERUPTION RELATED HELICOBACTER PYLORI ERADICATION THERAPY].

OBJECTIVES AND METHODS: The number of patients who undergo Helicobacter pylori (HP) eradication therapy has been increasing since it became covered by insurance in Japan. As such, an increasing number of patients develop drug eruption as a result of HP eradication therapy. In the present study, we describe the clinical course of 28 patients who were treated at our hospital for drug eruption following HP eradication therapy between April 2008 and March 2016. RESULTS AND DISCUSSION: The majority of the patients were women (21 women, 7 men). The average length of time from the start of treatment to the onset of eruption was 7.6 days. A drug-induced lymphocyte stimulation test (DLST) was performed in 10 patients. Amoxicillin was the most common cause of eruption, with 6 patients testing positive. Patients who were considered likely to have developed sensitivity prior to the treatment required the systemic administration of steroids. On the other hand, symptoms were relieved with topical steroids in some of the patients who were considered likely to have developed sensitivity during the course of treatment. CONCLUSION: Since penicillin antibiotics have long been used, some patients may have become sensitized without being aware of this. Our findings highlight the need for the careful management of patients developing sensitivity prior to treatment as they require the systemic administration of steroids.

Factors involved in the development of diaper-area granuloma of the aged.

An infant skin disease with clusters of nodules in the diaper contact area was reported as granuloma gluteale infantum. Recently, the number of elderly patients with this condition has increased, and it has been reported as diaper-area granuloma of the aged. These lesions are presumably caused by irritation from feces and urine. We observed similar cutaneous symptoms in six elderly patients, five of whom revealed clusters of nodules arranged in a circular pattern in the gluteal region presenting a peculiar clinical picture. They were all bedridden and wore cloth diapers. We speculate that wearing a cloth diaper seems to be a major factor behind this condition. Another factor was sitting during the day. A subject had lesions with nodules on the scrotum. The distribution of nodules appeared to be related to the body position and vigorous movement of the patient. In all cases, topical steroid therapies were not effective. They were all positive for bacteriuria. Chronic urinary tract infection further irritates the skin. It is necessary to reduce urine contact and keep the lesion clean.

Successful treatment for recurrence of primary cutaneous anaplastic large-cell lymphoma in elderly patient with etoposide, mitoxantrone, cyclophosphamide, vincristine, prednisolone and bleomycin (VNCOP-B) therapy.

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a malignant lymphoma with a relatively good prognosis, consisting of CD30-positive, undifferentiated, large cells. We report an elderly patient with C-ALCL which recurred after cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) therapy, but was effectively treated with the third-generation etoposide, mitoxantrone, cyclophosphamide, vincristine, prednisolone and bleomycin (VNCOP-B) regimen. It is characterized by the completion of treatment in 8 weeks, its applicability on an outpatient basis, and a low incidence of cardiotoxicity and mucosal symptoms. Although our patient had no side-effects during chemotherapy, patients should be carefully monitored for side-effects, especially infection. In conclusion, the VNCOP-B regimen might be an effective treatment for elderly patients with good performance status, CHOP-resistant patients or patients with aggressive non-Hodgkin's lymphoma.

Properties and histochemical application of a novel antibody against trichohyalin granules.

We obtained an antibody, anti-inner root sheath cells antibody (anti-IRSC Ab), that reacted with the inner root sheath (IRS) cells especially trichohyalin granules (THG). In order to compare the properties of anti-IRSC Ab and AE15, which is a specific monoclonal antibody against THG, histochemical and biochemical examinations were performed. In vivo localization with anti-IRSC Ab and AE15 indicated that both antibodies reacted with THG, but anti-IRSC Ab reacted with THG in the suprabulbar region of the Huxley layer, whereas AE15 reacted with THG in the suprabulbar region and upper bulbar portion of the Huxley layer, as shown by immunohistochemical and immunoelectron microscopic analyses. The results of immunoblot analysis showed that anti-IRSC Ab reacted with a protein spot at 45 kDa, pI 6.5, but AE15 reacted with high molecular weight proteins at pI 5.5. Furthermore, anti-IRSC Ab reacted with specimens of squamous cell carcinoma (SCC) but did not react with those of basal cell carcinoma (BCC). In contrast, AE15 reacted with neither SCC nor BCC. These findings suggest that anti-IRSC Ab and AE 15 recognized different component proteins in THG, and therefore indicated that THG, like as keratohyalin granules, might consist of several proteins. It is the novel finding that the anti-IRSC Ab positive substance in THG in the normal hair and SCC cells.

The presence of tryptase-positive and bikunin-negative mast cells in psoriatic skin lesions.

Human mast cells are well known to produce a serine protease, tryptase, which appears to play a pathogenic role in various skin inflammations. It was previously reported that a rat homologue of bikunin may inhibit tryptase activity. Various type of cells (i.e. keratinocytes) are able to produce this protein inhibitor, it still remains unclear if bikunin is present in dermal inflammatory milieu, in which mast cells, through secretion of tryptase, play an inflammatory role. Therefore, the purpose of the present study was to exploit expression and production of bikunin in dermis and dermal constituents. We first compared the dermal mast cells in psoriatic lesions with those in lesional skin of atopic dermatitis or of chronic eczema by use of immunoelectron microscopy and immunohistochemical analyses using antibodies to bikunin and tryptase. Then, we tested what kinds of cytokines may regulate the de novo synthesis of bikunin. To do so, RNA was extracted from a human mastocytic cell line, HMC-1, reverse-transcribed, and semiquantitative RT-PCR was performed using primers specific for bikunin. With immunoelectron microscopy, bikunin was found to localize on the cell membrane, while tryptase was in the secretary granules of the mast cells. In psoriatic lesions, around 70% of dermal mast cells were positive for both tryptase and bikunin, and the remaining was mostly positive for tryptase, but the expression of bikunin was under the detection limit of the experimental setting. This observation was seen in only psoriatic lesions, even in almost cured lesions, while in atopic dermatitis or chronic eczema only mast cells doubly positive for bikunin and tryptase were seen. In HMC-1, bikunin was constitutively expressed at an mRNA level, which was upregulated by stimulation with interleukine-4, but was suppressed by interferon-gamma. Bearing in mind the concept that in psoriasis local cytokine milieu is shifted toward a Th1 pattern (predominant secretion of interferon-gamma), tryptase-positive, bikunin-negative mast cells may be induced.

The receptor for erythropoietin is present on cutaneous mast cells.

Skin samples from patients with extra-mammary Paget disease, Bowen's disease, atopic dermatitis, psoriasis and non-lesional skin of nevus pigmentosus were immunohistochemically examined with an anti-soluble erythropoietin receptor antibody (anti-sEPOR antibody), and only the dermal mast cells positively stained in all skin samples were examined. These positively stained dermal cells were proved to be mast cells by double staining with anti-sEPOR antibody and either with anti-bikunin antibody or anti-tryptase antibody. Immunoelectron microscopically these EPOR were found in the secretory granules of the dermal mast cells. Further, EPOR in the mast cells may be consisting of only the extracellular domain of erythropoietin receptor molecule as the mast cells were immunohistochemically not reacted with an antibody to the C-terminal peptide of EPOR. Human mast cell line, HMC-1 cells has immunohistochemically the erythropoietin receptor, which was consisting of a 43 kDa major protein and a 20 kDa minor protein in the immunoelectrophoresis. These data may indicate that EPOR in the mast cells may not be the whole molecule, but probably the soluble one of EPOR.

A case of herpetiform pemphigus with anti-desmoglein 3 IgG autoantibodies.

Herpetiform pemphigus (HP) is a rare variant of pemphigus characterized by a unique clinical phenotype of erythematous or urticarial plaques and vesicles that present in a herpetiform arrangement. Most HP cases have circulating anti-desmoglein 1 (Dsg1) IgG autoantibodies, but some HP cases have anti-desmoglein 3 (Dsg3) IgG. A 92-year-old Japanese woman presented with severely pruritic annular erythema and vesicles in a herpetiform arrangement on the trunk. No oral mucosal lesions were present. Histopathologically, these vesicles showed eosinophilic spongiosis as well as suprabasilar acantholysis. Direct immunofluorescence showed in vivo IgG deposition on keratinocyte cell surfaces, and indirect immunofluorescence showed circulating IgG autoantibodies against keratinocyte cell surfaces at a titer of 1:30. Enzyme-linked immunosorbent assay using recombinant Dsg1 and Dsg3 revealed the presence of anti-Dsg3 IgG but no anti-Dsg1 IgG autoantibodies. The lack of oral mucosal involvement and the unique clinical features favored the diagnosis of HP. It remains to be clarified why the anti-Dsg3 IgG autoantibodies in this patient induced this unique features of HP, rather than the mucosal dominant type of pemphigus vulgaris.

Successful treatment of pulmonary metastasis and local recurrence of angiosarcoma with docetaxel.

Angiosarcoma of the face and scalp of the elderly frequently recurs locally, metastasizes early despite various treatments, and has a poor prognosis. We describe a patient who had angiosarcoma of the scalp with pulmonary metastasis. Local recurrence occurred after excision and local and arterial administration of IL-2. A weekly administration method of docetaxel was therefore selected, resulting in complete remission of the pulmonary metastasis and a partial response of the local recurrence. This favorable clinical outcome in our case suggests that docetaxel therapy may be an option for the treatment of angiosarcoma of the scalp with pulmonary metastasis.

Myoepithelioma possibly originating from the accessory parotid gland.

Myoepithelioma originates almost exclusively from myoepithelial cells of the salivary, prostate and mammary glands. The skin is a very rare site where myoepithelioma occurs. We describe a patient with a myoepithelioma on the right cheek seen as a subcutaneous nodule that was separated from the parotid gland at surgical resection. Histopathological findings were consistent with those of a myoepithelioma that had originated from the parotid gland, suggesting that this tumor may have developed from the accessory parotid gland.

Quantitative analysis of bikunin-laden mast cells in follicular eruptions and chronic skin lesions of atopic dermatitis.

Bikunin, an inhibitor of serine proteases, is widely distributed in human tissues, including the skin, and may inhibit tryptase and modulate allergic inflammation. The purpose of the present study was to compare follicular eruptions (FE), so-called atopic skin or perifollicular accentuation, with atopic dermatitis (AD) lesions (ADL) by immunohistochemical analysis using antibodies to bikunin and tryptase. Immunohistochemically, bikunin was colocalized with tryptase in dermal mast cells, and a small quantity of bikunin was also deposited in the intercellular spaces in FE and ADL. The number of bikunin-laden mast cells per 0.78 mm(2) of skin was 78.1+/-7.1 (mean+/-SEM, n=14) in FE, 25.4+/-2.3 (n=10) in normal skin from children and infants, 91.3+/-11.8 (n=10) in ADL, 25.6+/-4.8 (n=5) in nonlesional skin of AD, and 27.8+/-2.0 (n=13) in normal adult skin. The difference between FE and normal control skin from children and infants, between FE and nonlesional skin of AD, and between lesional and nonlesional skin of AD were significant. Based on the above findings and the occasional presence of spongiosis and lymphocyte infiltration, in FE moderate inflammation is apparent histopathologically even though little inflammation is apparent clinically.