Masaru Natsuaki

Immediate contact hypersensitivity induced by repeated hapten challenge in mice

An immediate reaction was investigated during repeated challenge testing for contact hypersensitivity to dinitrofluorobenzene ( DNFB) in BALB/c mice. The mice were sensitized to DNFB on back skin and repeatedly challenged with the same hapten on the left ear at 1 week intervals. The ear after the 5th challenge showed biphasic responses which consisted of an immediate and a delayed‐type reaction. The reactions were hapten specific. Mast cell‐deficient WBB6F1 W/WV mice did not show any immediate reaction, while congenic normal mice showed both immediate and delayed‐type reactions. Histologically, numerous dermal mast cells were found in the left ear of repeatedly challenged BALB/c and WBB6F1 normal mice, while there were few mast cells in the ear of WBB6F1 W/WV mice. Anti‐ DNP IgE antibodies were detected in BALB/c, WBB6F1 normal and W/WV mice after repeated challenge with DNFB. Intradermal injection of anti‐IgE antibodies in the repeatedly DNFB‐challenged ear elicited an immediate reaction. These results suggest that immediate contact hypersensitivity develops through the production of anti‐ DNP IgE antibodies and an increase in dermal mast cells after repeated challenge with DNFB.

Prevalence of kdr-like Mutations Associated with Pyrethroid Resistance in Human Head Louse Populations in Japan

ABSTRACT Pyrethroid insecticides play very important roles in the control of pediculosis, which is caused by human head louse (Pediculus humanus capitis De Geer) worldwide. The development of head louse resistance to pyrethroid pediculicides has become a global issue during the last two decades. Pyrethroid resistance is associated with amino acid substitutions in the &agr;-subunit of the para-sodium channel gene; these substitutions are termed kdr-like mutations. The frequencies of four mutations (D11E, M815I, T929I, and L932F) in the sodium channel gene were studied in human head louse colonies collected from Japan by using SNaPshot method. A total of 630 head lice collected from 282 infested people were analyzed, and it was found that 55 lice of 19 colonies homozygously or heterozygously possessed kdr-like genes, in which the four mutations existed concomitantly. This suggested that the quadruple mutant haplotype is a common feature of the kdr genes of pandemic head lice. The frequencies of the occurrence of resistant genes in the total individuals tested and resistant gene-carrying colonies were 8.7 (55/630) and 6.7% (19/263), respectively. Because the resistant gene was detected in the colonies collected from 11 of the 22 prefectures surveyed, it is speculated that resistant head lice are already spread extensively in Japan. This was the first large-scale survey of pyrethroid resistant head lice in Japan.

Non‐anogenital (ectopic) hidradenoma papilliferum with sebaceous differentiation: A case report and review of reported cases

Hidradenoma papilliferum is a benign tumor that usually occurs in the female anogenital region. We present a 52‐year‐old male with a non‐anogenital (ectopic) hidradenoma papilliferum on his face. He had had a subcutaneous tumor on his right eyebrow for 30 years. The histological findings included variously shaped cystic and tubular structures in the tumor. The lumina were surrounded by a double layer of cells and showed active decapitation secretion. The lesion contained sebaceous differentiation, which has not been previously documented in the histopathology of hidradenoma papilliferum. We review the published work of non‐anogenital (ectopic) hidradenoma papilliferum tumors on the head and neck.

Immediate and Delayed‐type Reactions in Caterpillar Dermatitis

The mechanism of dermatitis induced by Euproctis caterpillars has not been fully clarified, although mechanical stimulation by the spicules as well as chemical irritation by venomous components from spicules have been suggested to be involved. In this study, skin tests using venomous spicules and the venomous extract from the caterpillar of E. pseudoconspersa were carried out on a subject. The test site developed both immediate and delayed‐type reactions. Next, the crude extract was separated into 8 fractions (No. 1–8) using gel filtration HPLC, and a skin test using each fraction was performed in the same subject. The result showed that only fraction No. 3 caused reactions similar to those in crude venom extract. Then skin tests using the crude venom and fraction No. 3 were performed in 10 healthy volunteers. The skin reaction caused by crude venom was similar to that caused by fraction No. 3 in each subject. Two volunteers showed neither immediate nor delayed‐type reactions, 4 volunteers showed a delayed‐type reaction, and the other 4 showed both immediate and delayed‐type reactions. These results indicate that allergic reactions against venom released by the spicules play a role in the induction of dermatitis by E. pseudoconspersa caterpillars. Variations in the clinical course of individual patients may be attributable to differences in the state of sensitization to the venomous components.

Cutaneous Eruptions Induced by Granulocyte Colony‐stimulating Factor in Two Cases of Acute Myelogenous Leukemia

Recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) induced cutaneous eruptions in two cases of acute myelogenous leukemia. In both cases, the eruptions appeared during rhG‐CSF therapy for neutropenia induced by the remission‐induction chemotherapy and disappeared rapidly after the discontinuance of rhG‐CSF therapy. Histopathology of those eruptions revealed dermal cell infiltrations consisting of some neutrophils and atypical cells. It was interesting that, although there were no leukemic cells in the peripheral blood or bone marrow, eruptions containing many leukemic cells appeared. The mechanism of the appearance of these eruptions was unclear, but it was considered that a few leukemic cells might have responded to rhG‐CSF and proliferated in the skin.

Extracorporeal Monocyte Granulocytapheresis was Effective for a Patient of Erythema Nodosum Concomitant withUlcerative Colitis

Abstract:  We report an erythema nodosum (EN) patient whose condition becameapparent during the clinical course of ulcerative colitis (UC).The patient relapsed frequently in spite of taking a high dose adrenocorticalsteroid during his morbidity period of UC. Monocyte‐granulocytapheresis(M‐GCAP) was combined with 5‐aminosalicylic acid 2250 mg/dayperoral and once a day of steroid enema. Monocyte‐granulocytapheresiswas performed once a week for 5 weeks, and succeeded in inducingclinical remission for both UC and EN. The immunological and clinical connectionsbetween UC and EN have never been fully elucidated. In this case,because the symptoms of UC and EN revealed parallel improvementafter his inflammatory reaction had been brought under control by combining M‐GCAP therapy, we hypothesize that theonset of EN appeared as a result of the patients long‐term,treatment‐resistant immuno‐disturbance, which first appeared as symptomsof UC. Immunomodulative effects induced by M‐GCAP might help tocontrol other chronic non‐specific inflammations not concerned withtargeted organ(s).

Reactivity and Persistence of Local Immunological Memory on Murine Contact Hypersensitivity

In a rechallenge system examining murine contact hypersensitivity to DNFB in BALB/c mice, the reactivity to the specific antigen at the previously responded site and the persistence of an immunological memory were investigated. Flare‐up reactions were induced 4 weeks after the first challenge only at the previously responded site by local or systemic administrations of minute quantities of a specific antigen. The intensity of ear swelling was dependent on the quantity of applied antigen at the time of the rechallenge. The local hypersensitivity to the specific antigen observed in the previously responded site and the regional lymph node persisted for at least 1 year.

Case of tick-associated rash illness caused by Amblyomma testudinarium

We report a case of tick‐associated rash illness (TARI), a new clinical entity of erythema migrans associated with a tick bite without infection of Lyme borreliosis agent. The patient, a 53‐year‐old man, went hiking in a mountainous area of Minoh City, Osaka Prefecture in October 2012. An erythematous macule with itching and a biting tick was found on his left thigh 2 days later, which gradually expanded. On the first visit to our department at the fifth day after hiking, an erythematous macule of 10 cm was recognized around the bite site. He had no systemic symptoms, and laboratory data were within normal limits. The tick was identified as a nymph of Amblyomma testudinarium. Histopathologically, perivascular infiltrates, mainly consisting of T lymphocytes, were seen in the dermis. The skin rash disappeared within 2 weeks with no treatment. Serum antibody titers against Lyme disease borrelial and rickettsial agents on the first visit and 2 weeks later were negative. These results indicate that the skin lesion of TARI was not associated with borrelial or rickettsial infection but a T‐cell‐mediated allergic reaction to salivary gland substances of the tick.

Optimal patch application time in the evaluation of skin irritation

We investigated the optimum application for evaluating skin irritation response by using samples of irritants commonly used as additives in cosmetics and other common household products. We studied 47 volunteers (16 men and 31 women). We selected three types of surfactant, one moisturizer, one anti‐infective agent and one oil solution. Using Finn chambers on Scanpor tape, we performed the patch test. A total of 0.015 mL of each sample was applied to the Finn chamber. For liquids, circular filter paper was soaked in 0.015 mL of the sample. Samples were placed on the upper back of participants, and closed for 4, 24 or 48 h. A patch application time of 24 h is sufficient to detect primary skin irritation from irritants in cosmetics and other common household products. In addition, we found that skin irritation reactions were strongest at 24 h after patch removal and that the reaction tended to be weaker at 48 h after patch removal. Patch testing to evaluate irritants should be performed by means of a 24‐h patch test with a follow‐up reading at 24 h after patch removal. An application time of 24 h places less of a burden on patients than a 48‐h patch test.

Staphylococcal enterotoxin B enhances a flare-up reaction of murine contact hypersensitivity through up-regulation of interferon-γ

Background:  We often see aggravation of eczematous skin lesions associated with bacterial infection, but the mechanism of this phenomenon is unclear. Staphylococcus aureus is known to colonize on the eczematous lesion and produce some exotoxins, which act as bacterial superantigens.