Combination of skin-directed therapy and oral etoposide for smoldering adult T-cell leukemia/lymphoma with skin involvement.

Approximately 50% of patients with adult T-cell leukemia/lymphoma (ATLL) have skin involvement, and the smoldering, skin lesion-bearing cases are often treated with various skin-directed therapies, such as phototherapy and radiation therapy. Daily oral administration of etoposide plus prednisolone (EP) is also used for smoldering-type ATLL. However, it remains unclear whether these therapies improve patients' survival. We retrospectively analyzed the prognosis of patients with smoldering, skin lesion-bearing ATLL (n = 62), who were treated, as first therapy, with one skin-directed therapy (n = 29), oral EP alone (n = 14) or a combination of skin-directed therapy and oral EP (n = 19). Multivariate analysis revealed that the hazard ratios (HRs) for the overall survival (OS) and progression-free survival (PFS) with the combination therapy were significantly lower than those with the skin-directed therapy (HR 0.1, p = 0.001; HR 0.2, p = 0.002, respectively). These results suggest that the combination of skin-directed therapy and oral EP improves the clinical outcome of patients with smoldering, skin lesion-bearing ATLL.

[A case of dyshidrosiform pemphigoid].

We report a case of dyshydrosiform pemphigoid. Multiple small bullae were noticed in the bilateral hands and feet of an 85 year old Japanese male about 1 month before admission to hospital, and these lesions gradually worsened and expanded generally. Clinical appearance on the initial examination showed a collection of erosions, bullae, and pustules with haemorrhagic pompholyx. Serum anti-BP180 antibody index was more than 150. Histopathologic appearance of the bullous leision revealed a subepidermal bulla with an inflammatory infiltrate and fibrinous exudate, with aggregated eosinophils, neutrophils, and lymphocytes in the upper dermis. In direct immunofluorescence, the epidermal basement membrane was stained strongly for complement C3 and weakly for IgG. Based on these features, especially from the particular clinical aspects, we finally diagnosed one subtype of bullous pemphigoid, namely dyshidrosiform pemphigoid. Although he got better by orally taking steroids, the eruptions recurred just after tapering off. Thereafter, he died due to worsened general condition partly complicated by pancreatitis.

Type of skin eruption is an independent prognostic indicator for adult T-cell leukemia/lymphoma.

Cutaneous involvement is seen in ~ 50% of adult T-cell leukemia/lymphoma (ATLL) patients. We investigated the association between skin eruption type and prognosis in 119 ATLL patients. ATLL eruptions were categorized into patch (6.7%), plaque (26.9%), multipapular (19.3%), nodulotumoral (38.7%), erythrodermic (4.2%), and purpuric (4.2%) types. When the T stage of the tumor-node-metastasis-blood (TNMB) classification of mycosis fungoides/Sézary syndrome was applied to ATLL staging, 16.0% were T1, 17.7% T2, 38.7% T3, and 4.2% T4, and the remaining 23.5% were of the multipapular and purpuric types. For the patch type, the mean survival time (median survival time could not be estimated) was 188.4 months. The median survival times (in months) for the remaining types were as follows: plaque, 114.9; multipapular, 17.3; nodulotumoral, 17.3; erythrodermic, 3.0; and purpuric, 4.4. Kaplan-Meier curves of overall survival showed that the erythrodermic type had the poorest prognosis, followed by the nodulotumoral and multipapular types. The patch and plaque types were associated with better survival rates. Multivariate analysis demonstrated that the hazard ratios of the erythrodermic and nodulotumoral types were significantly higher than that of the patch type, and that the eruption type is an independent prognostic factor for ATLL. The overall survival was worse as the T stage became more advanced: the multipapular type and T2 were comparable, and the purpuric type had a significantly poorer prognosis than T1.

A case of laryngeal carcinoma in a young adult with dyskeratosis congenita.

Dyskeratosis congenita (DC) is an inherited disorder that is characterized by the triad of skin pigmentation, nail dystrophy, and mucosal leukoplakia. Individuals with DC suffer from premature mortality because of bone marrow failure, pulmonary disease, or malignant transformation within the areas of mucosal leukoplakia, caused by telomerase dysfunction. We present a case of a 31-year-old Japanese man with DC who developed laryngeal cancer (supraglottic T4aN0M0). To avoid the serious risks of accelerating the DC-associated complications by DNA-damaging therapies, he was treated with a total laryngectomy plus right modified neck dissection (levels IB, IIA, III, and IV). A contralateral nodal metastasis appeared 4 months after initial surgery and was salvaged by a left radical neck dissection. Our strategy to spare DNA-damaging therapies has proven effective so far. This is the first reported case of laryngeal cancer in a patient with DC in the English-language medical literature.

Photocontact dermatitis to ketoprofen presenting with erythema multiforme.

A 74-year-old Japanese man developed erythema multiforme on the inner aspect of his left elbow where ketoprofen-containing tape was applied and exposed to sunlight, and the eruption subsequently spread to the four limbs and trunk. The lesions were successfully treated with systemic corticosteroids without recurrence. Lymphocyte stimulation tests with ketoprofen-photomodified peripheral blood mononuclear cells revealed that the patient had circulating lymphocytes reactive with a photohaptenic moiety of ketoprofen. To our knowledge, this is the first case of erythema multiforme induced by photocontact dermatitis. The presence of circulating photoantigen-reactive T cells seemed to induce erythema multiforme as an unusual manifestation in this patient.

T cell populations propagating in the peripheral blood of patients with drug eruptions.

BACKGROUND: In the non-immediate type of drug eruptions, the populations of circulating T cells may be altered as a consequence of T cell responses to a culprit drug. OBJECTIVE: The aim of this study was to investigate differences among the types of drug eruptions in propagating T cell populations of the patients' peripheral blood. METHODS: The type of eruptions were divided into three categories: (1) generalized maculopapular eruption (MPE), (2) erythema multiforme (EM)/Stevens-Johnson syndrome (SJS), and (3) drug-induced hypersensitivity syndrome (DIHS) or drug rash with eosinophilia and systemic symptoms (DRESS). T cell populations were phenotypically analyzed by flow cytometry in the percentage of T helper (Th) 1 (CXCR3+CD4+), Th2 (CCR4+CD4+), Tc1 (CXCR3+CD8+), and Tc2 (CCR4+CD8+) subsets and their activation states as assessed by CD69, CD25 or HLA-DR positivity. RESULTS: Upon occurrence of both MPE and EM/SJS, Th2 cells outnumbered Th1 cells, whereas Tc1 and Tc2 cells differentially predominated in EM/SJS and MPE, respectively. An increase of HLA-DR+CD8+ cells in EM/SJS type provided another supportive evidence for Tc1 stimulation. In DIHS, during the development of the second wave of eruption and/or liver dysfunction associated with anti-HHV6 antibody elevation, CD4+ cells were gradually decreased, but CD8+ cells were inversely increased. Tc1 cells were increased as well as Th1 cells. Finally, in all the three groups, there existed a considerable number of CD25+CTLA-4-CD4+ T cells. CONCLUSION: Our study suggests that Th2/Tc2 and Th2/Tc1 cells mediate MPE and EM/SJS, respectively, and Tc1 cells are involved in the pathogenesis of DIHS at the late stage.

The various effects of four H1-antagonists on serum substance P levels in patients with atopic dermatitis.

Antiallergic drugs have various actions against allergy-associated cells and molecules as well as antihistamic properties. We studied the effects of antiallergics on the serum levels of substance P. Patients with atopic dermatitis were treated with one of four oral H1-antagonists for 14 days, and the serum level of substance P was measured before and after treatment in parallel with several atopic severity markers. Olopatadine significantly decreased the substance P level. This is in accordance with its known downmodulatory effect on tachykinin release. In contrast, cetiridine and fexofenadine unexpectedly increased the substance P level. In patients administered cetiridine, the blood severity markers for atopic dermatitis, including lactate dehydrogenase, eosinophil number, and the soluble forms of IL-2R, E-selectin, VCAM-1 and ICAM-1 were reduced after the treatment. Therefore, the elevation of SP was unrelated to the deterioration of atopic dermatitis but rather associated with improvement. Our study suggests that antiallergics can be divided into substance P-increasing and -decreasing types and raises the possibility that the increment of substance P by the former type is caused by the competitive occupation of substance P receptors.

[Four cases of non-clostridial gas gangrene with diabetes mellitus].

We report four cases of non-clostridial gas gangrene. All cases were associated with diabetes mellitus as the underlying disease. Case 1: a 60-year-old male developed an ulcerative lesion on the dorsum of his left foot. Peptostreptococcus asaccharolyticus, Citrobacter freundii and Staphyrococcus epidermidis were identified in culture from odoriferous pus. Case 2: a 81-year-old female developed a lesion on her vulva spreading to the right lower abdomen. Bacteroides bivius, Peptostreptococcus asaccharolyticus and Streptococcus faecalis were identified in culture of the odoriferous pus. Case 3: a 80-year-old male developed a swollen area with ulcer on the right foot. Bacteroides fragiris, Enterococcus faecalis, Proteus mirabilis, Enterococcus avium and Enterococcus faecalis were identified by culture. Case 4: a 52-year-old female developed swelling of her left groin. Enterococcus faecalis and Streptococcus anginosus were identified in culture from the odoriferous pus. In all patients, a radiological examination revealed the presence of subcutaneous gas in the lesion. Prognosis of non-clostridial gas gangrene is usually poor. These four patients, however, all survived. Once an infectious sign is seen in the diabetic patient, it is important to discover a gas figure by using the radiological examination (plain film or computed tomography). Earlier diagnosis and debridement are the most important for a better prognosis. Because workers with diabetes mellitus are now increasing in number, occupational physicians should always keep in mind that a serious infectious disease like non-clostridial gas gangrene can develop even from minor accidental trauma, and they should control the working environment in the workplace where accidents often happen.