Aiko Okazaki

Intravascular histiocytosis associated with rheumatoid arthritis: report of a case with lymphatic endothelial proliferation

cin: a clue to the pathogenesis of and therapy for scleroderma? Clin Immunol 2002; 102:209–16. 11 Passiu G, Cauli A, Atzeni F et al. Bleomycin-induced scleroderma: report of a case with a chronic course rather than the typical acute ⁄ subacute self-limiting form. Clin Rheumatol 1999; 18:422–4. 12 Berman B, Duncan MR. Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin. Br J Dermatol 1990; 123:339–46.

Identification of thymus and activation-regulated chemokine (TARC/CCL17) as a potential marker for early indication of disease and prediction of disease activity in drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS).

BACKGROUND Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a serious acute drug reaction with fever, cutaneous eruption, lymphadenopathy, and several visceral dysfunctions. Eosinophilia is a common hematological abnormality in DIHS/DRESS suggesting that the Th2-type immune response is involved. Thymus and activation-regulated chemokine (TARC/CCL17) is a family of CC chemokines known to play an important role in Th2-mediated immune-inflammatory processes. OBJECTIVE We investigated the pathogenic role of TARC in patients with DIHS. METHODS Sera were obtained from 8 patients with DIHS, 7 patients with Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN), and 14 patients with drug-induced maculopapular exanthema (MPE). Serum TARC levels were measured by ELISA. TARC levels were then compared with clinical symptoms and various hematological parameters. In addition, a biopsy was taken from the lesional skin of patients with DIHS and stained with anti-TARC Ab and anti-CD11c Ab. RESULTS Serum TARC levels in patients with DIHS were significantly higher than those in patients with SJS/TEN and MPE during the acute phase. Serum TARC levels in DIHS patients correlated with skin eruptions, serum sIL-2R levels, eosinophil counts, and serum IL-5 levels. Immunohistochemical staining revealed that TARC was mainly expressed on CD11c+ dermal dendritic cells in patients with DIHS. CONCLUSION Serum TARC levels may be associated with the initial presentation of DIHS as well as disease activity during the course. Thus, they could be useful as an indicator for early diagnosis and assessment of disease activity in DIHS. CD11c+ dendritic cells may be the main source of TARC in patients with DIHS.

Polymorphisms of HLA-DR and -DQ genes in Japanese patients with bullous pemphigoid.

Bullous pemphigoid (BP), an autoimmune skin disease of the elderly, is mediated by autoantibodies that bind to hemidesmosomes of epidermal basal cells. This study investigated BP‐associated HLA‐DR and ‐DQ genes among Japanese patients. We analyzed HLA‐DR and ‐DQ genes among 23 Japanese BP patients based on the polymerase chain reaction‐restriction fragment length polymorphism. Eighteen of these 23 patients (78%) carried at least one allele of HLA‐DRB1*04 or DRB1*1101, with significant increases in HLA‐DRB1*04 (*0403, *0406)/DQA1*0301/DQB1*0302 and DRB1*1101/DQA1*0505/DQB1*0302 haplotypes as well as the individual alleles DRB1*1101 and DQB1*0302 (corrected p<0.05 for each comparison), when compared to control subjects. These data differ from the accepted DQB1*0301 (DQ7) association with the same disease among Caucasians. These findings indicate that different HLA class II haplotypes genetically influence susceptibility to BP among different ethnic groups. Our findings, together with previous reports on Caucasian patients with the pemphigoid group of bullous diseases, suggest that HLA‐DRB1 molecules might participate in the regulation of autoimmune responses to BP antigens.

Dermatomyositis presenting as erythroderma

Dermatomyositis is a connective tissue disorder characterized by cutaneous and muscle involvement. 1 The characteristic and probably pathognomonic cutaneous features of dermatomyositis are the heliotrope eruption and Gottrons papules. Other features include poikiloderma, malar erythema, nailfold changes, and photosensitivity. We report the first case of dermatomyositis that presented initially as erythroderma.

An inverse correlation of VZV skin-test reaction, but not antibody, with severity of herpes zoster skin symptoms and zoster-associated pain

BACKGROUND Cell-mediated immunity (CMI) has been considered to be related to the development of herpes zoster (HZ). However, there have been no large-scale prospective studies on the relationship between VZV-specific CMI and severity of HZ. OBJECTIVE We carried out a large-scale prospective cohort study to clarify the relationship between immunological factors for varicella-zoster virus (VZV) and the clinical severity of HZ. METHODS We carried out a cohort study on VZV immunity in a population living on an island cluster, Shozu County in Japan, and examined the people who developed HZ during a median follow-up period of 2 years, with a focus on the relationship between cell-mediated and humoral immunity and the severity of skin lesions and zoster-associated pain. A total of 12,522 people over the age of 50 were enrolled in this study, and 258 registrants were diagnosed as HZ. CMI was measured by VZV skin test, and humoral immunity was assessed with serological tests (neutralization test, immunoadherence hemagglutination test, and gpELISA test) for VZV-specific antibodies. RESULTS CMI to VZV assessed by VZV skin test showed a significant inverse relationship to the severity of HZ skin lesions, and also to the severity of acute and subacute pain. Furthermore, weak response to the VZV skin test was associated with a high risk of post-herpetic neuralgia. In contrast, VZV-specific antibody titer was not associated with the severity of skin lesions and zoster-associated pain. CONCLUSION VZV-specific CMI, but not humoral immunity, may play a key role in controlling the severity of HZ skin lesions and zoster-associated pain.

Bullous Pemphigoid Associated with Shy‐Drager Syndrome

We report a patient with Shy‐Drager syndrome who developed multiple tense blisters mainly on the extremities. Circulating anti‐basement membrane zone autoantibodies were detected by the indirect immunofluorescence method. Immunoblot analysis using normal human epidermal extracts demonstrated that this patients serum reacted only with 230 kD bullous pemphigoid antigen (BPAG1). Concerning the pathoetiology of the association of bullous pemphigoid and Shy‐Drager syndrome, we discuss a sequence similarity between BPAG1 and dystonin, a candidate gene for dystonia musculorum.

VZV skin-test reaction, but not antibody, is an important predictive factor for postherpetic neuralgia

BACKGROUND The decline of cell-mediated immunity (CMI) is thought to be related to the risk of postherpetic neuralgia (PHN) as well as herpes zoster (HZ). However, the relationship between immunological condition and the incidence of PHN is still unclear. OBJECTIVE We conducted a large-scale prospective cohort study to clarify the relationship between immunological factors for varicella-zoster virus (VZV) and the incidence of PHN. METHODS We carried out a cohort study on VZV immunity in a population living on an island cluster, Shozu County in Japan, and examined the people who developed HZ during a follow-up period of 3 years, with a focus on the relationship between cell-mediated and humoral immunity and the incidence of PHN. A total of 12,522 people over the age of 50 were enrolled in this study, and 401 registrants were diagnosed with HZ, including 79 PHN cases. We evaluated anatomical location and severity of skin lesion, acute pain severity, presence or absence of abnormal sensations, CMI assessed by VZV skin test, and VZV-specific antibody titer measured by serological tests. RESULTS The incidence of PHN was significantly associated with a weak response to the VZV skin test, as well as facial or lumbosacral localization of skin rash, severe skin lesion, severe acute pain, and presence of abnormal sensations, but not related to VZV-specific antibody titer. CONCLUSION The incidence of PHN is significantly associated with the decline of VZV-specific CMI, but not related to VZV-specific humoral immunity.

CREEPING DISEASE DUE TO LARVA OE SPIRUROID NEMATODA

A 31‐year‐old man visited our hospital in May 1991, com‐plaining of an abdominal serpiginous eruption with pruritus (Fig. 1). He had eaten raw “firefly squid” (Watasenia scintil‐lans) 2 weeks before the onset of the disease, and the erup‐tion had grown to about 30 cm in length in 2 weeks. The laboratory findings included a leukocyte count of 6100/mm3 with 10% eosinophils and a serum IgE level of 134 U/mL (normal < 303 U/mL). The front of the eruption was excised. Seven parasitic sections were observed in the dermis (Fig. 2). The diameter of the sections were about 0.08 mm. The mus‐cle layer was of the polymyarian coelomyarian type. In the body cavity of the parasite, there was a glandular part of the esophagus composed of vacuolated cells with many nuclei and a narrow esophageal lumen. Well‐developed lateral nerve chords were also visible in these sections. Two of the parasitic sections showed intestine composed of cuboidal cells with a round lumen and lateral nerve chords of both sides touching each other in the center of body cavity.

Adult case of staphylococcal scalded skin syndrome differentiated from toxic epidermal necrolysis with the aid of dermoscopy.

Dear Editor, A 77-year-old man presented with subcutaneous masses in the right groin arising from the lymph nodes (LN), which were subsequently biopsied and diagnosed as diffuse large B-cell lymphoma. Due to pain at the biopsy site, the patient was administrated celecoxib on day 7 after biopsy. Five days later, he was hospitalized because of a fever of 37.7°C and erythroderma. He was initially diagnosed with drug eruption caused by celecoxib, and was i.v. administrated 125 mg/day of methylprednisolone sodium succinate for 3 days. However, the skin lesion rapidly extended to all over the body, followed by exfoliation. At this time, toxic epidermal necrolysis (TEN) was suspected and he was transferred to our hospital 5 days after the onset. On admission, he had diffuse erythema and exfoliation with a positive Nikolsky’s sign (Fig. 1a). Desquamation and a crust were present on the perioral region (Fig. 1b). The mucous membrane was not affected. Dermoscopy showed a fresh exfoliation site on the trunk that still had an epidermis with less leachate, suggesting subcorneal detachment (Fig. 1c). A skin biopsy specimen from the erythematous lesion of the trunk revealed subcorneal cleavage without epidermal necrosis (Fig. 1d). These findings were incompatible with TEN, but were consistent with late staphylococcal scalded skin syndrome (SSSS). His right groin was red and swollen. Computed tomography showed turbid adipose tissue around the inguinal LN from which methicillin-susceptible Staphylococcus aureus (MSSA) was isolated, suggestive of an abscess. We started the i.v. administration of vancomycin hydrochloride (2 g/day) and meropenem hydrate (1 g/day) on the day of admission. Seven days later, he had recovered well with improved skin findings. He was diagnosed with SSSS induced by MSSA infection in the right groin. The term “SSSS” was introduced in 1970 by Melish and Glasgow, who showed that it was caused by an infection with ET (exfoliative toxin)-producing strains of Staphylococcus aureus. A previous study reported that mortality was higher in adults (40%) than in infants. Therefore, it is important to