Efficacy of anifrolumab in long-term intractable alopecia due to discoid lupus erythematosus.

Alopecia associated with lupus erythematosus is broadly classified into reversible nonscarring alopecia seen in the acute phase, such as worsening of systemic lupus erythematosus (SLE) and cicatricial alopecia seen in chronic cutaneous lupus erythematosus represented by discoid lupus erythematosus (DLE). In DLE-induced alopecia, early therapeutic intervention before developing scarring alopecia is important, but the condition is often resistant to conventional treatment. Anifrolumab (ANI), a novel therapeutic agent for SLE that inhibits Type I interferon activity, has been shown to be effective against acute skin lesions, including alopecia, in patients with SLE. However, there are very few reports on the effect of ANI on alopecia due to DLE. We report on a 27-year-old Japanese woman with SLE whose alopecia due to chronic DLE was refractory to topical therapy and systemic therapy with oral glucocorticoid, multiple immunosuppressants, and belimumab for ∼8 years after onset and whose alopecia improved with ANI. ANI can be considered to be an effective treatment option in lupus patients presenting with alopecia due to DLE, even in the chronic refractory stage.

Single-cell RNA sequencing of mycosis fungoides reveals a cluster of actively proliferating lymphocytes.

A 70-year-old man's chronic erythematous skin lesion in the extremity had developed into a tumour one year before his first visit at our hospital. A biopsy showed atypical lymphocyte-like cells, and immunostaining identified atypical cells as CD3+, CD4+, CD5+ and FOXP3+. Single-cell RNA sequencing (scRNA-seq) analysis using BD Rhapsody revealed the higher expression of CD3, CD4, CD5 and FOXP3 genes in a group of cells that highly expressed genes, such as PCNA, in the S/M phase, which is in agreement with immunofluorescence staining results. The use of scRNA-seq analysis data is expected to promote personalised medicine for cutaneous lymphoma.

Effectiveness and safety of tacrolimus ointment combined with dupilumab for patients with atopic dermatitis in real-world clinical practice.

Atopic dermatitis (AD) is the most common inflammatory skin disease affecting people of all age groups worldwide. To our knowledge, there are currently no studies estimating the effectiveness of tacrolimus ointment and dupilumab as a combination therapy for AD. Thus, here we describe the effectiveness and safety of tacrolimus ointment in combination with dupilumab for facial rashes in patients with AD. Overall, we included 109 patients who newly received dupilumab from April 2018 to July 2020 in the Dermatology Department of Hyogo College of Medicine Hospital. Of them, 60 patients were treated with tacrolimus ointment. Specifically, of the 60 patients, 40 were treated with dupilumab in combination with tacrolimus ointment and topical steroids, whereas the remaining 20 were prescribed tacrolimus ointment alone and were further analyzed. The analysis showed that the combination does not cause serious side-effects at high frequency. The patients showed rapid improvement of facial dermatitis along with systemic dermatitis, and the rate of improvement of head/neck Eczema Area and Severity Index (EASI) score significantly correlated with the rate of improvement of overall EASI score. In addition, there was no complication of herpes simplex observed in these 20 patients. Thus, tacrolimus ointment combined with dupilumab is an effective and safe treatment option for facial AD.

Tick bites in Japan.

Ticks are blood-sucking ectoparasites belonging to the order Acarina, class Arachnida. In Japan, eight genera and 46 species are known. Tick bite patients frequently present to dermatology clinics. The main causative species of human tick bites are Ixodes persulcatus and Ixodes ovatus in northern to central Japan, and Amblyomma testudinarium and Haemaphysalis longicornis in western Japan. Tick bites often occur from April to September, particularly in May through July, consistent with the active period for ticks. Although erythema usually does not develop at the tick bite site, a small area of erythema may be seen in some cases. Occasionally, an erythema larger than 50 mm in diameter are formed at the bite site, known as tick-associated rash illness. It is thought that the erythema is a delayed-type allergic reaction to the substances in tick saliva. Repeated tick bites induce immunoglobulin E production against galactose-1,3-α-galactose, one of the substances in tick saliva, which may trigger an immediate allergic reaction. The most reliable method to remove a tick sucking blood is en bloc resection of the tick and surrounding skin under local anesthesia. Insect repellent spray containing icaridin or DEET are effective to prevent ticks from attaching and tick-borne infections. It is important to educate not only dermatologists but also the general public regarding tick bites.

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.

[Cutaneous necrotizing vasculitis in a patient with Behcet's disease; mimicking polyarteritis nodosa].

A 25-year-old-man was referred with an approximately 1-year history of recurrent fever, tonsillitis, testicular pain and testicular swelling in June 2009. He also complained of visual disturbance, some erythema nodosum (EN) like lesions on his lower extremities and oral aphthous ulcerations for 5 months. Opthalmological consultation confirmed retinochoroiditis, and ultrasonography revealed epididymitis. A biopsy of the EN like lesion showed a necrotizing vasculitis of the small and medium-sized vessels with septal panniculitis in the subcutis. The laboratory findings revealed an elevation of CRP and positive HLA-B51. He was diagnosed with incomplete Behcet's disease according to the Japanese criteria (1987). After the initiation of the therapy with 10 mg/day of prednisolone, his symptoms promptly ameliorated. In our case, although epididymitis as well as the histopathological findings suggested polyarteritis nodosa (PN), a diagnosis of BD was established on the basis of other contemporaneous findings. Necrotizing vasculitis as a cutaneous manifestation in patients with BD has been rarely reported. However, BD and PN, including cutaneous PN, have rarely described in conjunction. Therefore, we propose that PN-like necrotizing vasculitis might be the subtype of BD.

Prevalence of kdr-like mutations associated with pyrethroid resistance in human head louse populations in Japan.

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 alpha-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.

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

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. OBJECTIVES: To investigate the potential role of superantigens in chronic dermatitis, we investigated the effect of staphylococcal enterotoxin B (SEB) on the skin reaction, the proliferative response and the cytokine production of local lymph node cells in the mouse model of contact hypersensitivity reaction. METHODS: Sensitized BALB/c mice were repeatedly challenged with dinitrofluorobenzene (DNFB), and intravenously injected with SEB and dinitrobenzne sulfonic acid sodium salt (DNBS). The ear swelling response was measured after DNBS injection. Cervical lymph node cells of those mice were cultured with DNBS in vitro. Their proliferative responses and the production of cytokines were assessed. RESULTS: SEB markedly enhanced the flare-up reaction of ear swelling induced by DNBS, the proliferative response of lymph node cells and the production of IFN-gamma. In contrast, the production of IL-5 was decreased. CONCLUSIONS: The present study may provide some clues for elucidating the mechanism involved in the exacerbation of dermatitis associated with staphylococcal infection.

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.

Antigenicity and irritancy tests of leukocyte-reduction filters using animal models.

We experienced a patient who showed severe allergic symptoms immediately after blood transfusion using a filter for removal of leukocytes. To investigate the cause of this incident, we conducted a maximization test on the antigenicity of substances extracted from filters used for leukocyte removal. The tests were performed in guinea pigs. Acetone extracts were obtained from filters made by three manufacturers (A, B and C) and sensitization and evocation were tested at 10% concentration. It was confirmed that extracts from one filter (B) induced sensitization in guinea pigs. Sensitization of the extracts was also tested at 1%, 0.1% and 0.01%, and was induced at 1% but not at 0.1% and 0.01%. Next, skin irritation and sensitization of the substances were tested using mice. 5%-ethanol extracts were prepared from filters made by 2 manufacturers (A and B) and the extracts (5% or 0.5% concentrations) were injected intradermally into the auricle and the ear swelling was observed 1, 24 and 48 hours and 7 days after injection. Significant ear swelling was induced by the extracts from B-filters. In the skin sensitization test, 5% extracts were injected subcutaneously into the back of mice for 3 continuous days for sensitization, and 0.5% extracts were injected intradermally into the auricle of mice to evoke a response, after which changes in ear swelling were observed. Biphasic ear swelling observed 1 hour (immediate response) and 24 hours (delayed response) after challenge was induced by the extracts from B-filters. In conclusion, our study showed that filters used for leukocyte removal may contain substances that cause skin irritation and sensitization and that antigenicity and irritancy tests of the filters might prevent the adverse reactions after blood transfusion.

[Three cases of centipede allergy--analysis of cross reactivity with bee allergy].

BACKGROUND: We experienced three cases of patients who suffered from systemic urticaria and systemic symptoms such as general fatigue and dyspnea which occurred just after the sting of centipede. The result of prick test by centipede venom revealed positive reaction in all three patients, so we diagnosed the symptoms of them as immediate type allergic reaction against centipede venom. And more there have been some reports documented the relationship between centipede allergy and bee allergy, so we added the examination about bee allergy on these three patients. METHODS: The measurement of bee venom specific IgE was practiced on all three patients and intradermal skin test about bee venom was done only on one patient. Moreover we also practiced prick test of centipede venom against another three patients who were diagnosed as having bee allergy. RESULTS: All patients of centipede allergy showed positive reaction for the specific IgE antibody of Wasp and/or Honeybee and one patient who was practiced skin test also reacted positively against Wasp and Yellow Jacket venom. But none of three patients of bee allergy showed positive reaction against centipede venom. CONCLUSION: According to these results we suspected that there lies some relationship between centipede allergy and bee allergy. But it is supposed that only little involvement of centipede allergy was concerned among the patients of bee allergy. Until now there have been only a few reports as to the centipede allergy. But actually we guess it may be the phenomenon that could occur frequently.

Extracorporeal monocyte granulocytapheresis was effective for a patient of erythema nodosum concomitant with ulcerative colitis.

We report an erythema nodosum (EN) patient whose condition became apparent during the clinical course of ulcerative colitis (UC). The patient relapsed frequently in spite of taking a high dose adrenocortical steroid during his morbidity period of UC. Monocyte-granulocytapheresis (M-GCAP) was combined with 5-aminosalicylic acid 2250 mg/day peroral and once a day of steroid enema. Monocyte-granulocytapheresis was performed once a week for 5 weeks, and succeeded in inducing clinical remission for both UC and EN. The immunological and clinical connections between UC and EN have never been fully elucidated. In this case, because the symptoms of UC and EN revealed parallel improvement after his inflammatory reaction had been brought under control by combining M-GCAP therapy, we hypothesize that the onset of EN appeared as a result of the patient's long-term, treatment-resistant immuno-disturbance, which first appeared as symptoms of UC. Immunomodulative effects induced by M-GCAP might help to control other chronic non-specific inflammations not concerned with targeted organ(s).

Distinction between well-differentiated liposarcoma and intramuscular lipoma by power Doppler ultrasonography.

BACKGROUND: This study evaluates the feasibility of ultrasonography in the distinction between well-differentiated liposarcoma (WDLS) and intramuscular lipoma (IL). MATERIALS AND METHODS: Three WDLSs and 9 ILs were included. Gray scale images were assessed for echogenicity, textural pattern and margins. Power Doppler ultrasonography was used to assess the number of detectable flow velocity signals in a 3 x 3 cm area. Furthermore, the ratio of the area occupied by colour flow signals relative to the selected area was determined. RESULTS: Gray scale images showed no differences between WDLSs and ILs. However, power Doppler showed more than 2 flow velocity signals in all WDLSs, whereas only 11% of the ILs had 2 signals. In all WDLSs, colour flow signals occupied more than 30% of the selected area. In contrast, ILs were characterized by a low color-dot ratio. Histologically, increased vascularity was found close to malignant cell invasions. CONCLUSION: Power Doppler ultrasonography is feasible to evaluate increased vascularity and thus differentiate WDLSs from ILs.

Flare-up reaction on murine contact hypersensitivity. III. Effect of staphylococcal enterotoxin B.

Staphylococcal enterotoxin B (SEB), a bacterial superantigen, is known as an immunomodulator because it activates an extremely large number of T-cells, and induces the production of large amounts of cytokines. In this study, we examined the effects of SEB on the contact hypersensitivity reaction (CHR). BALB/c mice were first sensitized through haptens applied to the back, and CHR was then induced through challenge to the left ear using the same haptens. SEB was administered intravenously 4 weeks later, causing a flare-up, peaking at 24 h post-administration, in the left ear that had previously exhibited CHR. This flare-up reaction was hapten non-specific, and was inhibited by anti-mouse tumor necrosis factor (TNF)-alpha antibodies. The flare-up was also suppressed by the oral administration of cyclosporin A prior to the administration of SEB. These results suggest that SEB induces a flare-up of CHR via the production of TNF-alpha.