Nail squamous cell carcinoma: A hidden high-risk human papillomavirus reservoir for sexually transmitted infections.

Human papillomavirus (HPV) causes cervical cancer, anal cancer, vulvar cancer, vaginal cancer, penile cancer, and oropharyngeal cancer. Squamous cell carcinoma (SCC) in the genital region in particular is recognized to be caused by HPV infection, and intraepithelial lesions of the penis and vulva are termed penile intraepithelial neoplasia and vulvar intraepithelial neoplasia, respectively. Although SCC of the nail apparatus is recognized as being associated with high-risk HPVs, it is not well-known in general medicine, and its analysis has been insufficient. In this article, we reviewed 136 cases of HPV-associated nail SCC and SCC in situ and delineated their clinical characteristics. We found that half of the cases were high-risk HPV-associated. Almost all of the types were high-risk α-HPVs. This disease had a male dominance and left hand digit 3 and right hand digits 1-3 were typically affected. In this review, 24% of the cases of nail SCC had a history of other HPV-associated diseases, suggesting the possibility of genitodigital transmission. We propose that nail SCC is a hidden high-risk HPV-associated reservoir and should be recognized as a sexually transmitted infection.

Lichenoid drug eruption with palmoplantar hyperkeratosis due to imatinib mesylate: a case report and a review of the literature.

Cutaneous adverse effects of imatinib mesylate (Glivec) are common and various types of skin eruptions have been reported. We report here a 57-year-old man who presented with lichen planus-like lesions on his extremities and palmoplantar hyperkeratosis due to the use of imatinib mesylate for chronic myeloid leukaemia. The skin lesions improved after discontinuation of imatinib mesylate but re-administration of the drug at a lower dose provoked a mild recurrence. He could, however, continue to take the drug at the lower dose and his skin lesions were well-controlled by topical corticosteroid treatment. The literature on lichenoid drug eruption due to imatinib mesylate is reviewed.

Digital gangrene in systemic lupus erythematosus.

Digital ulcers and gangrene are common skin manifestations of connective tissue diseases, especially systemic sclerosis, although they are relatively rare in systemic lupus erythematosus. We describe here three patients with digital gangrene and systemic lupus erythematosus. None of the patients showed high disease activity of systemic lupus erythematosus at the time the digital gangrene developed. Two patients were positive for anti-RNP antibodies; however, no symptoms of other collagen diseases were present. One patient had anti-phosphatidylserine/prothrombin complex antibodies, and the other had anti-cardiolipin beta2 glycoprotein I antibodies and lupus anticoagulant at low titre. All patients showed narrowing or occlusion of radial and/or ulnar arteries in addition to digital arteries. Although a complication of anti-phospholipid syndrome is considered to be a possible cause, there may be unidentified causes other than thrombosis, atherosclerosis, overlap syndrome and vasculitis.

Cutaneous manifestations and histological features of microscopic polyangiitis.

Purpura and livedo are common cutaneous manifestations of microscopic polyangiitis (MPA); however, only a few clinical analyses focusing on the relationship between clinical symptoms and the affected vessels in the skin have been reported. We herein report the cutaneous manifestations and histological features of four patients with MPA. In two patients, a Henoch-Shönlein purpura-like eruption developed with necrotizing vasculitis localized in the upper dermis. The other two patients presented with livedo racemosa; with histological findings of necrotizing vasculitis of the small vessels around the muscle fibers or from the deep dermis to subcutaneous tissue. Two patients' cases were complicated by systemic sclerosis and had poor prognoses. MPA can present with various cutaneous manifestations. Additional research is required to ascertain the relationship between the prognosis and the affected vessels.

Eosinophilic fasciitis: report of two cases and a systematic review of the literature dealing with clinical variables that predict outcome.

We reported two patients with refractory eosinophilic fasciitis (EF) and provided a systematic review of the literature to determine the clinical variables associated with prognosis of EF. We enrolled 88 cases, whose clinical characteristics were analyzed by separating the patients into two or three groups based on outcome. The incidence of certain clinical and pathological features differed among the groups. In particular, the incidence of morphea-like skin lesions in patients with refractory fibrosis was significantly higher than in patients without refractory fibrosis (p = 0.003). Patients with morphea-like skin lesions were 1.9 times more likely to develop persistent fibrosis than patients without these lesions (95% confidence intervals, 1.5-2.5). A younger age (under 12 years) at onset was associated with a 1.6 times greater risk of residual fibrosis (95% confidence interval, 1.1-2.2). Trunk involvement was associated with a 1.4 times greater risk of residual fibrosis (95% confidence interval, 1.0-2.0). Histopathologically, the presence of dermal fibrosclerosis was associated with a 1.4 times greater risk of refractory fibrosis (95% confidence interval, 1.0-2.1). We consider these clinical characteristics, notably the presence of morphea-like skin lesions may be an important risk factor for developing residual fibrosis in EF patients.

Effects of an Alkaline Diet on EGFR-TKI Therapy in EGFR Mutation-positive NSCLC.

BACKGROUND: The acidic tumor microenvironment is associated with progression of cancers. The purpose of this study was to investigate the association between an alkaline diet and the effect of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Eleven advanced or recurrent NSCLC patients with EGFR mutations treated with EGFR-TKI after being instructed to follow an alkaline diet were retrospectively evaluated. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 19.5 (range=3.1-33.8) and 28.5 (range=15.4-46.6) months. The average dosage of EGFR-TKI was 56±22% of the standard dosage. Urine pH was significantly increased after the alkaline diet (6.00±0.38 vs. 6.95±0.55; p<0.05). CONCLUSION: An alkaline diet may enhance the effect of EGFR-TKI treatment in NSCLC patients with EGFR mutations.

Preventive effects of topical washing with miconazole nitrate-containing soap to diaper candidiasis in hospitalized elderly patients: A prospective, double-blind, placebo-controlled study.

The objective of the present randomized, double-blind trial was to evaluate the efficacy and safety of daily washing with miconazole nitrate-containing soap for candidiasis at diaper-covered sites in elderly subjects under long-term inpatient care. To confirm the onset and disappearance of candidiasis, we microscopically evaluated the existence of the pseudohyphae and/or blastoconidia of Candida spp. We enrolled 75 elderly patients who wore diapers all day in the hospital or nursing home. Patients were randomly assigned to receive treatment with either miconazole soap or miconazole-free placebo soap, and 28 patients in the miconazole group and 27 patients in the placebo group were followed for 4 weeks. Although washing with miconazole soap did not affect the frequency of pseudohyphae/blastoconidia-positive patients, it significantly inhibited the positive conversion of pseudohyphae/blastoconidia compared with the placebo group. As a result, the frequency of patients positive for pseudohyphae/blastoconidia was significantly lower in the miconazole group than in the control group at 4 weeks (17.9% vs 44.4%). Clinically apparent diaper candidiasis did not develop in either group. Washing with miconazole soap was a significant independent factor for reducing the cases positive for pseudohyphae/blastoconidia, while diarrhea and heart failure were significant factors associated with an increase in the positive rate at the end-point. Severe adverse effects were not found in any patients. Thus, washing with miconazole soap is well-tolerated and can inhibit the positive conversion of Candida in patients wearing diapers. Therefore, maintenance of genital hygiene using this soap may prophylactically decrease the overall prevalence of patients with diaper candidiasis.

Daily versus intermittent application of high-concentration tacalcitol ointment in combination with low-dose cyclosporin for psoriasis vulgaris.

In this study, we aimed to compare the clinical effectiveness of highly-concentrated tacalcitol ointment daily versus intermittent application in patients with psoriasis vulgaris who simultaneously took a low dose of cyclosporin. All the patients in both groups showed significant improvements, and the patients in the intermittent application group obtained more patient satisfaction in cost performance. The treatment cost of low-dose cyclosporin and intermittent application of highly-concentrated tacalcitol ointment was less than half of that of high-dose cyclosporin and daily application of highly-concentrated tacalcitol ointment. This preliminary study suggests that the combination therapy with low-dose cyclosporin administration and intermittent application of highly-concentrated tacalcitol is effective, safe and provides acceptable costs for the treatment.

Adult-onset Still's disease with prurigo pigmentosa-like skin eruption.

A 34-year-old woman with adult-onset Still's disease (AOSD) developed prurigo pigmentosa-like lesions on her chest and upper back in addition to the typical rash of AOSD. A biopsy specimen taken from the upper back showed characteristic features of prurigo pigmentosa. The eruption and fever subsided immediately after the administration of 40 mg/day prednisolone, but arthralgia persisted even after intravenous pulse methylprednisolone therapy in combination with immunosuppressive drugs. Various atypical skin rashes, including prurigo pigmentosa-like lesions, have been reported in association with AOSD. Therefore, one should carefully follow the clinical course of a patient in order not to overlook these atypical cutaneous manifestations of AOSD.

The antipsoriatic effect of thiamazole is not accompanied either by significant changes in blood lymphocyte subsets nor by serum concentration of TNF-alpha.

It has been reported that the antithyroid thiourethylenes, propylthiouracil and methimazole can bring about significant clinical improvement in patients with psoriasis vulgaris. In this paper, we reconfirmed the clinical usefulness of the antithyroid drug thiamazole, which is similar to methimazole, in Japanese patients with psoriasis vulgaris. We further asked whether the clinical improvement was linked to the changes in some immunological parameters or not. To answer this question, we analyzed peripheral blood lymphocyte subsets and measured serum concentrations of TNF-alpha and IL-1beta in 13 patients with psoriasis vulgaris before and during thiamazole administration. The mean percentage of CD4+ HLA-DR+ lymphocytes in the patients was constantly elevated before and 12 weeks after the administration. The patients treated with thiamazole showed a significant increase in the ratio of CD4+/CD8+ at the 4th week, though it declined at the 8th and 12th week. Other lymphocyte subsets showed no significant change during the treatment. The concentrations of serum TNF-alpha exhibited no significant change during thiamazole administration. Serum concentration of IL-1beta was under the detection level. These results indicate that thiamazole may improve the psoriatic lesion via other immune mechanisms, or the effects can not be reflected by the peripheral lymphocyte subsets and cytokine which we investigated.

Clinical usefulness of a long-term treatment with an antithyroid drug for psoriasis vulgaris.

We have previously reported that an antithyroid thiourethylene, thiamazole, can bring about significant clinical improvement in patients with psoriasis vulgaris. Although the efficacy of antithyroid thiourethylenes had been reported earlier, few studies have evaluated the safety of its long-term use. In this study, we aimed to study whether or not long-term thiamazole administration is complicated by any adverse effects. Eight patients with psoriasis vulgaris were enrolled in this study after informed consent was obtained. Each patient was administered thiamazole orally at 30 mg/day for 12 weeks. Two patients achieved complete clearance of psoriatic lesions. Four patients showed a significant improvement, and two patients did not reach satisfactory improvement. Some adverse effects developed in five patients; serum TSH levels elevated above the normal range in three patients and fell below the normal range in one patient. However, serum free-T3 and free-T4 levels remained within normal ranges during the treatment in all patients, and none of the patients developed clinical hypothyroidism. This preliminary study suggests that thiamazole administration is an effective and relatively safe treatment for patients with psoriasis vulgaris.

Clinical analysis of leg ulcers and gangrene in rheumatoid arthritis.

Leg ulcers are often complicated in patients with rheumatoid arthritis (RA), however, the etiology is multifactorial. We examined the cases of leg ulceration or gangrene in seven RA patients who were hospitalized over the past 3 years. One patient was diagnosed as having pyoderma gangrenosum. Although vasculitis was suspected in three patients, no histological evidence was obtained from the skin specimens. In these patients, angiography revealed the stenosis or occlusion of digital arteries. In the remaining three patients, leg ulcers were considered to be due to venous insufficiency. Treatment should be chosen depending on the causes of leg ulcers.

Clinical follow-up study of adult-onset Still's disease.

Eighteen patients with adult-onset Still's disease have been followed up for 3-22 years in our department. Initial manifestations were fever with skin rash in 14 patients, fever, skin rash and sore throat in two, skin rash in one and arthralgia in one. During the follow-up period, typical skin rash was seen in all patients, of them five patients (29%) revealed atypical skin rash simultaneously. Atypical rash included persistent erythema with pigmentation in two, persistent plaques and papules with linear erythema in two and edema of the eyelids mimicking dermatomyositis in one. Persistent papules and plaques revealed histologically characteristic features, such as dyskeratotic keratinocyte and liquefaction degeneration as well as a sparse superficial dermal infiltrate containing scattered neutrophils. In patients of chronic articular type and polycyclic systemic type, atypical skin rash, lymphadenopathy and hyperferritinemia were noted to be significantly higher than those of monocyclic type. These factors might be prognostic factors of adult-onset Still's disease in our study.

Bosentan for digital ulcers in patients with systemic sclerosis.

Recurrent digital ulcers are manifestations of vascular disease in patients with systemic sclerosis (SSc). We report six patients with severe digital ulcers who were treated with bosentan administered p.o., 62.5-125 mg daily. The mean duration from the diagnosis of SSc to the initiation of bosentan was 9.5 years, and the observation period after bosentan administration was from 7 months to 4.5 years. In case 1, neither new digital ulcers nor Raynaud's phenomenon developed for 4.5 years. In case 2, digital ulcers recurred after the discontinuation of bosentan; however, re-administration of bosentan lead to the improvement. In cases 3-5 with recurrent digital ulcers, no new lesions have developed. In these five patients, pain evaluated by visual analog scale was significantly reduced. In three patients, bosentan was discontinued because of severe liver dysfunction. These results suggest that bosentan is an effective treatment for refractory digital ulcers associated with SSc; however, liver function should be carefully monitored. Compared to the doses of bosentan used to treat pulmonary hypertension, relatively lower doses may effectively control painful digital ulcer/gangrene in patients with SSc.

Clinical usefulness of a supplementary cyclosporin administration with a topical application of maxacalcitol ointment for patients with moderate psoriasis vulgaris.

In this study, we aimed at confirming the clinical usefulness of a supplementary additional cyclosporin microemulsion preconcentrate (CyA MEPC) administration in 15 patients with psoriasis vulgaris whose disease activity had been unchanged or exacerbated with topical maxacalcitol treatment. Each patient took a supplementary CyA MEPC administration, 2.5 mg/kg per day in addition to maxacalcitol ointment therapy. When the Psoriasis Area and Severity Index (PASI) score revealed over a 75% decrease against the initial value, the administration of CyA MEPC was tapered off, and a topical application of maxacalcitol ointment was continued for the maintenance phase. All patients could obtain improvement within 12 weeks. In 12 patients whose PASI score reduced over 75%, CyA MEPC was tapered off. Of those, five patients remained in remission by maxacalcitol ointment for over 12 months and three patients for 6 months. In conclusion, this preliminary study may suggest that supplementary therapy of short-term CyA MEPC administration in combination with topical vitamin D3 treatment may be worth trying for patients with moderate psoriasis vulgaris.

Association of antiphosphatidylserine/prothrombin antibodies with neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE) are well-recognized symptoms although the pathophysiology of neuropsychiatric SLE (NPSLE) is unclear. Since an association with antiphospholipid antibodies has been reported, we examined the prevalence of antiphosphatidylserine-prothrombin antibodies (anti-PS/PT Abs), lupus anticoagulant (LA), anticardiolipin/beta2-glycoprotein I antibodies (anti-beta2-GPI Abs), and antiribosomal P protein antibodies (antiribosomal P Abs) in 68 SLE patients and analyzed their associations with neuropsychiatric manifestations. The prevalence of LA was significantly higher in the patients with neuropsychiatric (NP) features than those without NP features (P < 0.02). The levels of anti-PS/PT antibody were also significantly higher in the patients with NP features than those without NP features (P < 0.01). The results indicate that LA positivity and higher levels of anti-PS/PT antibody can be predictive markers for NPSLE.