Aya Nishizawa

Psoriasiform drug eruption due to abatacept.

A 59-year-old woman presented with a 4-month history of erythematous plaques on her palms and extremities. The patient had a long-term history of using methotrexate (8 mg/week) and oral prednisolone (10 mg/day) as therapy for RA, which had been diagnosed at the age of 37. Laboratory findings were as follows: white blood cell count 10,300 /μl; C-reactive protein 1.27 mg/ dl (normal < 0.3 mg/dl); anti-nuclear antibody × 40; rheumatoid factor 68 IU/ml (normal < 20 IU/ml); rheumatoid arthritis particle agglutination × 320 (normal < × 40); autoantibody to galactose-deficient IgG 74.9 AU/ml (normal < 6 AU/ml); and matrix metalloproteinase-3 195 ng/ml (normal 17.3–59.1 ng/ ml). Three years previously, the patient had enrolled in a clinical trial to study the effects of abatacept (750 mg/day, once every 4 weeks). The patient’s clinical symptoms of RA were well-controlled with abatacept, and thus oral prednisolone was ceased approximately 4 months before her admission to our department. Physical examination revealed that erythematous plaques of various sizes with scales were present on the patient’s extremities, palms and soles (Fig. 1). Microscopically, there was a parakeratotic hyperkeratosis with irregular acanthosis and a localized thinning of the granular layer (Fig. 2A). Cellular infiltrate comprising mononuclear cells and a few neutrophils was found around perivascular areas in the upper dermis. Inflammatory cells infiltrated into the epidermis and an accumulation of neutrophils in the cornified layer was found (Fig. 2B). The patient had no medical or family history of psoriasis. The eruptions were initially resistant to topical corticosteroids, but gradually improved within a few weeks. Skin patch-testing with abatacept (10% and 20%) was negative. After the remission of skin symptoms, abatacept was re-administered, resulting in the recurrence of skin symptoms within a few days. The patient is being controlled with reduced doses of abatacept (less than 500 mg/day) together with occasional use of topical corticosteroids.

Syringoid eccrine carcinoma with apparently aggressive transformation: case report and review of the literature

A 65‐year‐old man presented with a 20‐year history of a lesion on his lower abdomen. The lesion had started as an indolent papule that slowly developed to form an extensive plaque. Physical examination revealed a flat‐topped, elevated, well‐demarcated, erythematous plaque measuring 7 cm × 5 cm in diameter ( Fig. 1 ). The lesion had an elastic, hard induration beneath the plaque and was fixed to the underlying tissue. Inguinal lymphadenopathy was present. Hematologic and biochemical investigations were all within the normal ranges. The patient underwent incision biopsy.

A de novo missense mutation in the keratin 13 gene in oral white sponge naevus

White sponge naevus (WSN; OMIM 193900) is a rare autosomal dominant disorder characterized by variable, and at times extensive, leucokeratosis of the oral mucosa. In some cases, the nasal, oesophageal and anogenital mucosa may be similarly affected. Histologically, involved mucosa shows a characteristic basket-weave or cell-within-cell appearance. Recent study has shown that keratin 4 (K4) and keratin 13 (K13) gene mutations are associated with WSN. Thus far, four pathogenic mutations have been identified in K4 and five in K13 in patients with WSN, and all these mutations were identified in familial cases of WSN. Clinically, oral manifestations seen in WSN resemble those found in mucosal disorders such as lichen planus and candidiasis. Therefore, it is not always easy to diagnose a patient with sporadic WSN with no family history of the disorder. Here we report a novel de novo missense mutation in KRT13 identified in a sporadic case of WSN.

Cowden syndrome: a novel mutation and overlooked glycogenic acanthosis in gingiva

Cowden syndrome (CS; OMIM 158350) is a rare genetic disorder that is characterized by multiple hamartomas (affecting various organs derived from all three germ layers) and an increased risk of some cancers, in particular thyroid and breast cancers. The lifetime risks for thyroid and breast cancer are estimated to be 3–10% and 25–50%, respectively. Characteristic mucocutaneous manifestations include multiple facial trichilemmomas, oral mucosal papillomatoses and acral keratoses. These clinical findings, as well as other hamartomatous or carcinomatous lesions, usually become evident in adulthood. CS is caused by mutations in the PTEN gene (phosphatase and tensin homologue deleted from chromosome 10), which encodes a dual phosphatase that signals down the phosphoinositol3-kinase ⁄Akt pathway and exerts G1 cell cycle arrest and apoptosis. PTEN mutations also cause a subset of Bannayan– Riley–Ruvalcaba syndrome (BRRS; OMIM 153480). BRRS has not been associated with malignant lesions. It was proposed that CS and BRRS result from germline mutations in a common gene (PTEN), and thus should be classified as PTEN hamartoma tumour syndromes (PHTS). The genetic mechanism by which mutations in a single gene cause such a diverse number of phenotypes is largely unknown. Here, we report a novel single nucleotide duplication in the PTEN gene in a de novo case of CS, in which mutational analysis was helpful in confirming the clinical diagnosis. Interestingly, in this case, the histopathological findings of mucosal papillomatosis contrasted with those that are generally recognized in cases of CS.

Haber’s syndrome may be a clinical entity different from Dowling–Degos disease

cytosis in adults: report from the International Registry of the Histiocyte Society. Eur J Cancer 2003; 39:2341–8. 10 Allen CE, McClain KL. Langerhans cell histiocytosis: a review of past, current and future therapies. Drugs Today (Barc) 2007; 43:627–43. 11 Lahey ME. Histiocytosis X: comparison of three treatment regimens. J Pediatr 1975; 87:179–83. 12 Aricò M, Colella R, Conter V et al. Cyclosporine therapy for refractory Langerhans cell histiocytosis. Med Pediatr Oncol 1995; 25:12–16. 13 Rodriguez-Galindo C, Kelly P, Jeng M et al. Treatment of children with Langerhans cell histiocytosis with 2-chlorodeoxyadenosine. Am J Hematol 2002; 69:179–84. 14 Dufresne AG Jr, Malcomb AW, Salhany KE, King LE Jr. Histiocytosis X mimicking the follicular occlusion syndrome: response to local therapy. J Am Acad Dermatol 1987; 16:385–6.

Anti-tumor effects of inactivated Sendai virus particles with an IL-2 gene on angiosarcoma

Cutaneous angiosarcoma is a life-threatening tumor that is resistant to conventional therapies. The therapeutic effects of Sendai virus particles (hemagglutinating virus of Japan envelope: HVJ-E) carrying IL-2 gene (HVJ-E/IL-2) were examined in a mouse model of angiosarcoma. Intra-tumoral injection of HVJ-E/IL-2 effectively inhibited the growth of angiosarcoma cells (ISOS-1) inoculated in mice and improved tumor-free rates. HVJ-E/IL-2 stimulated local accumulation of CD8 (+) T cells and NK cells and reduced regulatory T cells in regional lymph nodes. Notably, the prevalence of myeloid-derived suppressor cells was lower in HVJ-E/IL-2-treated mice than in HVJ-E-treated mice. HVJ-E/IL-2 treatment promoted IFN-γ production from CD8 (+) T cells in response to tumor cells, more significantly than HVJ-E treatment. Greatly improved tumor-free rates were obtained when sunitinib, a tyrosine kinase inhibitor, was administered in combination with HVJ-E/IL-2. Immunogene therapy with HVJ-E/IL-2 with or without sunitinib could be a promising therapeutic option for cutaneous angiosarcoma.

Hydroa vacciniforme with mucosal involvement and recalcitrant periodontitis and multiple virus re-activators after sun-exposure.

An 8-year-old boy presented with hydroa vacciniforme with recurrent oral mucosal ulcers and treatment-resistant gingivitis/periodontitis. Symptoms of oral mucosal involvement and gingivitis/periodontitis mirrored the severity of the skin lesions in sun-exposed areas. Although Epstein-Barr virus was negative in the skin lesions, Epstein-Barr virus DNA was detected in the gingival lesions when skin disease activity increased. Human herpes viruses-6 and -7 were also positive in the gingival lesions. Notably, human parvovirus B19 DNA was detected in both skin and gingival lesions. Impairment of systemic immunity was not detected. This report describes a rare case of hydroa vacciniforme with mucosal involvement and periodontal disease accompanied by multiple local virus re-activation.

Close association between metal allergy and nail lichen planus: detection of causative metals in nail lesions

Background  Lichen planus (LP) is a common skin disorder of unknown aetiology that affects the skin, mucous membranes and nails. Although metal allergies have been implicated in the development of oral LP (OLP), the contribution of these allergies to nail LP (NLP) has yet to be studied in detail.

Erythrodermic Psoriasis Improved by Panitumumab, But Not Bevacizumab

Psoriasis is considered to be a disease mediated by Th17/Th1 immunity, with the production of interleukin (IL)-17, IL-22, and interferon (IFN)-γ. Previous evidence has also demonstrated the possible involvement of epidermal growth factor receptor (EGFR) ligands and vascular en-dothelial growth factor (VEGF) (1–5). Panitumumab is a human monoclonal antibody targeting EGFR. On the other hand, bevacizumab is a humanized monoclonal antibody that binds VEGF. Here, we observed clinical effects of these antibodies administered for rectal cancer in a patient with psoriasis.CASE REPORTA 77-year-old man presented with a 35-year history of psoriasis, which was diagnosed at the age of 41 years. The patient had been treated with topical cor-ticosteroids, activated vitamin D3 analogue ointment, oral etretinate, and psoralen plus ultraviolet A (PUVA) therapy, which resulted in only partial and transient improvement. At the age of 65 years, the skin symptoms worsened and became erythrodermic (Fig. 1A–C). At the age of 67 years, he developed rectal cancer that was treated surgically. However, due to subsequent multiple metastases to the lung and lymph nodes, mFOLFOX6 therapy (modified combination therapy of folinic acid and fluorouracil with oxaliplatin) in combination with bevacizumab (anti-vascular endothelial growth factor (anti-VEGF) antibody, 290 mg/day, 2-week intervals) was initiated and continued for 20 months, but it failed to inhibit tumour progression. Treatment with CPT-11 (irinotecan) in combination with bevacizumab for an additional year was also ineffective. Subsequently, chemotherapy was changed to CPT-11 and panitu-mumab (anti-EGFR antibody, 290 mg/day, 2-week intervals). Notably, when panitumumab was first given, the erythrodermic eruption showed dramatic impro-vement within approximately 10 days after treatment (Fig. 1D), despite the fact that bevacizumab had been ineffective for skin symptoms. Although a few small psoriatic lesions recurred periodically within 2 weeks, subsequent administration of panitumumab cleared the skin lesions, and the skin symptoms are currently well controlled together with the metastatic tumour lesions. Therapeutic effects on skin symptoms lasted at least 6 months after the initiation of panitumumab therapy.DISCUSSIONPsoriasis is a chronic skin disease involving kera-tinocyte proliferation, altered differentiation, and vascularization. EGFR and its endogenous ligands are over-expressed in skin lesions and serum in psoriasis (5, 6), leading to keratinocyte proliferation. Levels of

Four Different Tumors Arising in a Nevus Sebaceous.

Nevus sebaceous is known by its association with one or more secondary tumors, but more than three multiple tumors arising from a nevus sebaceous is extremely rare. A 67-year-old female presented with a light brown plaque on the back of her head that contained a dome-shaped black node and an erosive lesion. Histopathological examination showed atypical basaloid cells in the black node. At the periphery of that node, structures resembling follicular germs extruded from interlacing cords in the upper portion and tumor nests with sebocytes were in the lower portion. In the erosive lesion, papillated structures with an apocrine epithelium were observed. In the light brown plaque, enlargement of sebaceous lobules was noted. From those histopathological features, a diagnosis of syringocystadenoma papilliferum, sebaceoma, trichoblastoma and basal cell carcinoma arising from a nevus sebaceous was made. We discuss the rarity of multiple tumors arising from a nevus sebaceous.