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Background: Congenital ichthyoses (CIs) adversely affect quality of life (QOL) in patients. However, the effects of CIs on patient QOL have not been studied sufficiently. Objective: To investigate the association between disease severity and QOL in patients with harlequin ichthyosis (HI) and ichthyosis: syndromic forms (ISFs) Methods: Clinical information of patients with HI and ISFs from 2010 to 2015 were obtained from 100 dermatology departments/divisions of principal institutes/hospitals throughout Japan. We examined the relationship between disease severity and QOL in patients with HI and ISFs. Patients who were aged 8 years or older and participated in a multicenter retrospective questionnaire survey in Japan were assessed by dermatology life quality index (DLQI, range of 0–30) and clinical ichthyosis score (range of 0–100). Results: Netherton syndrome patients had a significantly higher risk of allergy to food or environmental allergens than patients with other phenotypes. Keratitis-ichthyosis-deafness (KID) syndrome patients showed a significantly higher risk of skin infections than patients with other phenotypes. Complete data on DLQI were obtained from 13 patients, whose median age was 21 (8–71) years. Nine patients were male, and 4 were female. Systemic retinoids were administrated to 2 of the 3 HI patients. The Spearman’s correlation coefficient between the clinical ichthyosis score and DLQI was 0.611 (P, ファイル公開：2019-11-01

Linear immunoglobulin (Ig)A/G bullous dermatosis (LAGBD) is an autoimmune bullous disease characterized by formation of subepidermal blisters and linear deposition of IgA and IgG antibodies along the basement membrane zone (BMZ). The association between linear IgA bullous dermatosis and ulcerative colitis (UC) is well recognized, but reports of UC-associated LAGBD are lacking. We have reported a 24-year-old man suffering from LAGBD associated with UC, which occurred before exacerbations of skin rash. A skin biopsy indicated a subepidermal blister with an infiltration of primarily neutrophils and eosinophils in the dermis. Direct immunofluorescence (IF) studies showed a linear deposition of IgA, IgG and C3c. Indirect IF of human skin revealed IgA and IgG anti-BMZ autoantibodies. Indirect IF of 1 M NaCl-split human skin demonstrated reactivity of IgA and IgG antibodies at the epidermal side. Immunoblotting showed that IgG antibodies reacted to the BP180 NC16a domain and 120-kDa linear IgA dermatosis-1, and enzyme-linked immunoassay detected IgG anti-BP230 antibodies. Administration of prednisolone and diaminodiphenyl sulfone (DDS) via the p.o. route improved skin lesions and bowel conditions. These results suggest that the bowel inflammation observed in UC may have a causative effect of initiation of the immune response to the skin and development of the bullous skin lesions in LAGBD. A combination of DDS and corticosteroid could be a recommended therapeutic option for patients with LAGBD with UC.

We herein report the case of a patient with adult-onset Satoyoshi syndrome. Alopecia was detected on the patient's head, left leg and abdomen, with pigmentation on the left thigh and abdomen. Painful muscle spasms were also noted in the abdomen and left upper and lower extremities, and a sensory disturbance was present in the left thigh. A skin biopsy of this field showed lymphocyte infiltration, and the patient was found to be positive for antinuclear antibodies and rheumatoid factor. These clinical findings were atypical, as they were lateralized. This case is the first report of Satoyoshi syndrome associated with a sensory disturbance. The patient's histological findings and positivity for autoantibodies indicated the presence of immunological abnormalities in this case of Satoyoshi syndrome.

Here, we describe a patient with disseminated systemic nocardiosis. He had a history of systemic lupus erythematosus and had received oral prednisolone for 7 months. Nocardia farcinica was isolated from the pus. There were neither clinical nor radiologic features of pulmonary nocardiosis. The patient was treated with oral trimethoprim/sulfamethoxazole, intravenous imipenem and surgical drainage with a good clinical response, and there has been no recurrence of the infection.

Background Recent reports have shown a correlation between extensive Mongolian spots and mucopolysaccharidosis type II (Hunter syndrome). However, a statistical survey of the incidence and natural history of extensive Mongolian spots among the patients with Hunter syndrome is lacking. Objectives To determine the prevalence of extensive Mongolian spots, to determine the natural course of the spots according to age in Japanese patients with Hunter syndrome, and to compare them with the results obtained from the patients’ brothers who did not have Hunter syndrome. Patients/Methods Fifty-two males with Hunter syndrome aged 3 to 40 years were studied. Twenty-five patients were examined in two clinics to determine the existence and characteristics of the spots. We interviewed their families about the spots in their neonates and the natural course of the spots according to their ages. The same survey was done among another 27 patients using a mailed questionnaire to their families. As control, we investigated 21 brothers of the patients by a mailed questionnaire to their families. Results The extensive Mongolian spots are identified in almost all the infants with Hunter syndrome and disappear extremely later in their life. The lesions had a high incidence of deep-blue hyperpigmentation. Regardless of age, the overall incidence was 78%. All of the brothers who did not have Hunter syndrome had common-type Mongolian spots in neonates, which regressed during their childhood. Conclusion Our results confirm a strong correlation between extensive Mongolian spots and Hunter syndrome for the Japanese population. The presence of extensive Mongolian blue spots should alert the physician to the possibility of Hunter syndrome.

Background: Werner’s syndrome, a rare autosomal recessive disorder, is characterized by features of premature aging. Seventy-five percent of the alleles of Japanese patients with Werner’s syndrome have one of three major mutations. Objective: To determine the genotype of a patient with Werner’s syndrome. Methods: We diagnosed Werner’s syndrome in a 47-year-old Japanese man who had juvenile cataracts, skin sclerosis and hyperpigmentation of the feet, a high-pitched voice, characteristic bird-like appearance of the face with a beak-shaped nose, thinning of the skin over the whole body and hyperkeratoses on the soles of the feet, hyperlipidemia, and diabetes mellitus. None of his immediate family had entered into a consanguineous marriage. He had undergone surgery to treat duodenal perforation. We screened his family for three major mutations (mutations 1, 4, 6) in the WRN gene by polymerase chain reaction-restriction fragment length polymorphism. Automated DNA sequencing fluorescence-labeled dideoxy terminators proceeded for abnormally migrating bands. Results: The patient and his mother had mutation 1 (nonsense mutation) in one chromosome. Although mutations 4 and 6 were undetectable, screening for mutation 4 revealed an abnormally migrating band. Consequently, we discovered a novel 4-bp deletion in exon 25 only in the patient. This mutation was not detected in any other family member. Conclusion: This is the first description of a patient with Werner’s syndrome who has a compound heterozygote of mutation 1 and a novel deletion mutation.

We report a rare autopsy case of disseminated strongyloidiasis combined with cytomegalovirus co-infection involving a 68-year-old man, who was originally from Okinawa Prefecture in southern Japan, where strongyloidiasis occurs sporadically among the elderly. This patient was admitted with a diagnosis of drug eruption and hypereosinophilic syndrome. He was administered steroid therapy, but suffered complications of fever, respiratory distress, and pulmonary hemorrhaging. The autopsy findings showed disseminated strongyloidiasis in the alveolar spaces and the intestine and cytomegalovirus inclusion body foci in the lungs.

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and life-threatening cutaneous adverse drug reactions. While there is no established therapy for SJS/TEN, systemic corticosteroids, plasma exchange and i.v. immunoglobulin (IVIG) have been used as treatment. The efficacy of IVIG is still controversial because total doses of IVIG used vary greatly from one study to another. The aim of this study was to evaluate the efficacy of IVIG, administrated for 5 days consecutively, in an open-label, multicenter, single-arm study in patients with SJS or TEN. IVIG (400 mg/kg per day) administrated for 5 days consecutively was performed as an additional therapy to systemic steroids in adult patients with SJS or TEN. Efficacy on day 7 of IVIG was evaluated. Parameters to assess clinical outcome were enanthema including ophthalmic and oral lesions, cutaneous lesions and general condition. These parameters were scored and recorded before and after IVIG. We enrolled five patients with SJS and three patients with TEN who did not respond sufficiently to systemic steroids before IVIG administration. All of the patients survived and the efficacy on day 7 of the IVIG was 87.5% (7/8 patients). Prompt amelioration was observed in skin lesions and enanthema in the patients in whom IVIG therapy was effective. Serious side-effects from the use of IVIG were not observed. IVIG (400 mg/kg per day) administrated for 5 days consecutively seems to be effective in patients with SJS or TEN. IVIG administrated together with steroids should be considered as a treatment modality for patients with refractory SJS/TEN. Further studies are needed to define the therapeutic efficacy of IVIG.

Ulcerative colitis (UC) is a clinical form of inflammatory bowel disease. The association of pyoderma gangrenosum or erythema nodosum with UC is well known. In addition, pustular eruption has been reported in UC. We describe a patient with UC who exhibited subcutaneous abscesses, as well as pustular eruption with a clinical course paralleling that of UC exacerbation.

Dendritic cells (DC) play a crucial role in the pathogenesis of oral lichen planus (OLP) with respect to antigens presented to T cells. We performed immunohistochemical analysis to elucidate the process of activation of DC in OLP.Thirty biopsy specimens were obtained from the patients with OLP. The expressions of CD1a, Langerin, S-100, fascin, chemokine receptor-7 (CCR-7), D2-40, cyclooxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) in DC from OLP and disease free control were investigated using specific antibodies. The distribution and number (1 mm(2)) of DC were assessed in the intra-epithelium and the submucosa specimens. Correlation between the number of DC and epithelium thickness was also determined.Immature DC (Langerin(+), CD1a(+), and S-100(+)) were identified in the epithelia from OLP patients and control, though the numbers of Langerin(+) and CD1a(+) positive cells were decreased in the OLP samples as compared to the control. Mature DC (fascin(+)) were identified in the submucosa specimens, not found in the epithelium from OLP or control. Double immunostaining revealed DC positive for fascin and CCR-7 in the submucosa, which had migrated into D2-40(+) lymph vessels. Furthermore, keratinocytes expressed both Prostaglandin E(2) (PGE(2)) converting enzymes, COX-2, and mPGES-1, indicating PGE(2) synthesis in the epithelial layer of the OLP specimens.Our results indicate that DC change from immature to mature in the epithelium and are then drawn out to the submucosa. We demonstrate that mature DC localized in the submucosa, it consequently migrates into lymph vessels. This maturation process of DC is an important immunopathological feature of OLP.

We report a case of a 69-year-old man with Schonlein-Henoch purpura who developed diffuse pulmonary hemorrhage. He complained of dyspnea and hemoptysis while he was treated with steroids for gastroenteropathy associated with Schonlein-Henoch purpura. The drop in his hemoglobin levels and diffuse ground-glass opacity at all levels of the lung fields on chest computed tomography were a significant clue to diagnosis. Despite pulse therapy, no clinical improvement of the lung was achieved, and he died on the 36th day after the admission. Although the combination of the corticosteroid and immunosuppressive agents is normally recommended, diffuse pulmonary hemorrhage could become a fatal complication in elderly Schonlein-Henoch patients.

For an evaluation of the preoperative assessment of subungual glomus tumours, a non-invasive examination of the lesion is desirable. Previous studies, however, have not clearly demonstrated these findings. We examined two cases of subungual glomus tumours and applied the approximately 5-14 MHz broadband B-mode and C-mode ultrasound imaging methods combined with Color Doppler imaging (CDI) and B-flow imaging (BFI) to clarify the significance of the preoperative assessment. We confirmed the tumour's localization, size and depth, using B-mode and C-mode imaging; and tumour vascularity using CDI and BFI. BFI is a newly developed ultrasound technique that enhances the B-mode imaging quality of the blood flow, including high-frame-rate and high-spatial-resolution imagings. BFI revealed the exact fine blood vessels within the subungual small tumour with no blooming compared to CDI. Our results indicate that these ultrasound scanning imagings are non-invasive and nonionizing evaluation methods, and that an accurate preoperative diagnosis using these methods will result in more effective surgical excision and relief.

Psoriatic onycho-pachydermo-periostitis (POPP) is a rare manifestation of psoriatic arthritis that is often misdiagnosed as a nail infection. The treatment for POPP has not yet been established.We present a case of a 67-year-old man who had no psoriatic skin lesions with POPP, characterized by psoriatic nail changes, painful swelling of the distal soft tissues on the great toes and fingers, and enthesopathies of the involved terminal phalanges. The clinical nail and arthritic changes were improved with methotrexate treatment 4 mg weekly for 6 months.Methotrexate can be recommended as the first-choice therapeutic agent for patients with POPP.

Buschke-Ollendorff syndrome is an autosomal dominant disease characterized by disseminated connective tissue nevi of elastic type and osteopoikilosis. We report a 6-year-old Japanese boy with connective tissue nevi that showed slightly grouped yellowish or skin-colored papules and nodules, distributed from birth over his right thigh, right buttock, and back. Radiologic skeletal survey revealed osteopoikilosis. A skin biopsy specimen obtained from a papule showed that collagen bundles in the dermis were thickened and homogenized. The elastic fibers were not increased but were coarse and clumped. The boy's father, at age 34, has had osteopoikilosis and similar papules and nodules on his left buttock and back for the preceding 18 years. We studied the paternal grandfather, aged 65. He had osteopoikilosis and similar skin lesions on his lumbar region. None of the three had a history of hearing loss or malignant tumor. To our knowledge, this is the first report of three generations of Buschke-Ollendorf syndrome in a Japanese family.

Hematopoietic stem cell transplant (HSCT) has been performed on patients with Hunter's syndrome. If applied, evaluation of recovery in various organs is needed for long-term follow-up. However, it remains unclear whether HSCT is effective against the neurological involvement in Hunter's syndrome, and morphological evaluation of recovery is inconsistent. We observed the degree of cutaneous nerve involvement in patients with Hunter's syndrome ultrastructurally before and after HSCT. Electron microscopic studies revealed that membrane-bound clear vacuoles were still observed in the cytoplasm of endoneurial fibroblasts and Schwann cells 2 months and 2 years, respectively, after HSCT. On the other hand, only a few vacuoles were present in dermal fibroblasts at 2 months after HSCT, and these disappeared within 2 years. These results suggest that the persistence of clear vacuoles in endoneurial fibroblasts and Schwann cells indicates a disturbed internal condition in the endoneurium 2 years after HSCT. Skin biopsies can be used in patients with Hunter's syndrome to study peripheral nerves for long-term follow-up to evaluate morphological efficacy.

Summary Background Hunter's syndrome is associated with several cutaneous findings. For instance, papules with ‘pebbly’ appearance are a specific marker for the disease. However, it remains uncertain whether they disappear after haematopoietic stem cell transplant (HSCT). Objectives To investigate the papules with ‘pebbly’ appearance before and after HSCT in infants with Hunter's syndrome, and to clarify the effect of HSCT on papules. Patients We observed five Japanese boys with Hunter's syndrome who had received HSCT at 4–11 years of age. Results The post-HSCT physical examinations revealed that papules disappeared completely within 35 days after the transplant with progressive reduction of cutaneous tightness in all the patients. Histochemical findings showed that papules contained a large amount of hyaluronic acid in the extracellular materials of the dermis and sulphated acid mucopolysaccharides in dermal fibroblasts before HSCT. Conclusions These results suggest that papules with a ‘pebbly’ appearance fade away through the digestion of a large amount of hyaluronic acid in cutaneous tissues by normal tissue histiocytes or enzymes of donor origin at an early stage after HSCT.

SummaryBackground The importance of early diagnosis in infants with a mild form of Hunter's syndrome should be emphasized. If applied sufficiently early, haematopoietic stem cell transplantation (HSCT) or recombinant enzyme therapy may improve the prognosis. At present, however, diagnosis of the mild form of Hunter's syndrome tends to be delayed, especially in infants with relatively normal intelligence. Objectives To investigate the occurrence of Mongolian spots in infants with Hunter's syndrome, and to clarify the relationship between the Mongolian spots and Hunter's syndrome clinically and histopathologically. Methods Seven Japanese boys with Hunter's syndrome who had received HSCT at ages 4–11 years were observed. The cutaneous manifestations of Mongolian spots before HSCT were evaluated, and compared with those after HSCT. In two patients, the hyperpigmentation from the Mongolian spots was examined by light and electron microscopy. Results Pre-HSCT observation revealed that all the patients had an extensive Mongolian spot. These were present at birth and have shown no signs of resolution during the post-HSCT period. Electron microscopic findings showed that pigment-bearing dermal melanocytes contained many free melanosomes in stage IV. These were surrounded by extracellular sheaths and encircled by elastic fibres. Conclusions Our results indicate a strong clinical correlation between the extensive Mongolian spots and Hunter's syndrome. Ultrastructural findings also clearly suggest that the hyperpigmentation is a long-lasting symptom. The recognition of the extensive Mongolian spots is essential as it may lead to early diagnosis in patients with a mild form of Hunter's syndrome.