Special Issue "Molecular Studies of Dermatitis: From Mechanism to Therapy".

Dermatitis (eczema) represents a group of inflammatory cutaneous diseases [...].

A step-by-step approach for assessing acute oral toxicity without animal testing for additives of quasi-drugs and cosmetic ingredients.

Animal testing of cosmetic ingredients and products has been banned in the European Union since 2013. However, in Japan, the application of new quasi-drugs requires the generation of data on acute oral toxicity through animal testing. A weight of evidence approach for assessing oral toxicity was challenged. This approach used a combination of safety data, including a neutral red uptake cytotoxicity assay using BALB/c3T3 cells (3T3-NRU cytotoxicity assay), which can assess the acute oral toxicity of quasi-drugs or cosmetic ingredients. We conclude that the step-by-step approach can be used to assess test substances that cause low acute oral toxicity, such as the median lethal dose (LD 50) > 2000 mg/kg, thereby avoiding animal testing.

Sarcoidosis and sarcoidal foreign body reaction after permanent eye makeup application: Analysis by immunohistochemistry with commercially available antibodies specific to Cutibacterium acnes and Mycobacteria.

We report two cases of eyebrow granulomas in patients who underwent a permanent eye makeup procedure. A rash was observed 16 months after the procedure in Case 1, and 10 years after the procedure in Case 2. Histopathologically, both patients exhibited noncaseating epithelioid cell granulomas. In Case 1, most of the black-brown granules of the permanent makeup were not present in the granulomas but were localized in the upper dermis. In contrast, in Case 2, some of the black-brown granules were phagocytized in the granulomas, preferentially within the giant cells. Based on systemic examinations, the patients from Cases 1 and 2 were diagnosed with sarcoidosis and sarcoidal foreign body reaction, respectively. To clarify the pathogenesis of our cases, we performed immunohistochemistry using commercially available monoclonal antibodies specific to Cutibacterium acnes, previously Propionibacterium acnes (PAB), and Mycobacteria (LAM antibody). PAB antibody results were positive in granulomas only in Case 1, and the LAM antibody results were negative in both cases. Immunohistochemical detection of C. acnes in granulomas could provide useful information for differentiating between cutaneous sarcoidosis and sarcoidal foreign body reactions.

Patch testing with the Japanese baseline series 2015: A 4-year experience.

BACKGROUND: The Japanese baseline series (JBS), established in 1994, was updated in 2008 and 2015. The JBS 2015 is a modification of the thin-layer rapid-use epicutaneous (TRUE) test (SmartPractice Denmark, Hillerød, Denmark). No nationwide studies concerning the TRUE test have previously been reported. OBJECTIVES: To determine the prevalence of sensitizations to JBS 2015 allergens from 2015 to 2018. METHODS: We investigated JBS 2015 patch test results using the web-registered Skin Safety Care Information Network (SSCI-Net) from April 2015 to March 2019. RESULTS: Patch test results of 5865 patients were registered from 63 facilities. The five allergens with the highest positivity rates were gold sodium thiosulfate (GST; 25.7%), nickel sulfate (24.5%), urushiol (9.1%), p-phenylenediamine (PPD; 8.9%), and cobalt chloride (8.4%). The five allergens with the lowest positivity rates were mercaptobenzothiazole (0.8%), formaldehyde (0.9%), paraben mix (1.1%), mercapto mix (1.1%), and PPD black rubber mix (1.4%). CONCLUSIONS: Nickel sulfate and GST had the highest positivity rates. The JBS 2015, including a modified TRUE test, is suitable for baseline series patch testing.

The efficacy of a multidisciplinary team approach in critical limb ischemia.

The aim of the present study was to clarify the characteristics of Japanese critical limb ischemia (CLI) patients and analyze the rates of real-world mortality and amputation-free survival (AFS) in all patients with Fontaine stage IV CLI who were treated with/without revascularization therapy by an intra-hospital multidisciplinary care team. All consecutive patients who presented with CLI at Showa University Fujigaoka Hospital between April 2008 and March 2014 were prospectively registered. The intra-hospital committee consisted of cardiologists, plastic surgeons, dermatologists, diabetologists, nephrologists, cardiovascular surgeons, and vascular technologists. The primary endpoint of this study was all-cause mortality and AFS during the follow-up period. The present study included 145 patients with Fontaine stage IV CLI. The mean age was 76.5 ± 10.2 years. The all-cause mortality rate during the follow-up period (15.5 ± 16.1 months) was 21.4 %. The AFS rate during the follow-up period (14.1 ± 16.4 months) was 58.6 %. A multivariate Cox proportional hazards regression analysis found that age >75 years and hemodialysis were significantly associated with all-cause mortality; and that age >75 years, Rutherford 6, and wound infection were significantly associated with AFS. A multidisciplinary approach and comprehensive care may improve the outcomes and optimize the collaborative treatment of CLI patients. However, all-cause mortality remained high in patients with Fontaine stage IV CLI and early referral to a hospital that can provide specialized treatment for CLI, before the occurrence of major tissue loss or infection, is necessary to avoid primary amputation.

A case of subepidermal blistering disease with autoantibodies to multiple laminin subunits who developed later autoantibodies to alpha-5 chain of type IV collagen associated with membranous glomerulonephropathy.

We report a 68-year-old Japanese female patient with subepidermal blistering disease with autoantibodies to multiple laminins, who subsequently developed membranous glomerulonephropathy. At skin disease stage, immunofluorescence demonstrated IgG anti-basement membrane zone antibodies reactive with dermal side of NaCl-split skin. Immunoblotting of human dermal extract, purified laminin-332, hemidesmosome-rich fraction and laminin-521 trimer recombinant protein (RP) detected laminin γ-1 and α-3 and γ-2 subunits of laminin-332. Three years after skin lesions disappeared, nephrotic symptoms developed. Antibodies to α-3 chain of type IV collagen (COL4A3) were negative, thus excluding the diagnosis of Goodpasture syndrome. All anti-laminin antibodies disappeared. Additional IB and ELISA studies of RPs of various COL4 chains revealed reactivity with COL4A5, but not with COL4A6 or COL4A3. Although diagnosis of anti-laminin γ-1 (p200) pemphigoid or anti-laminin-332-type mucous membrane pemphigoid could not be made, this case was similar to previous cases with autoantibodies to COL4A5 and/or COL4A6.

Metal patch test results from 1990-2009.

Although metals are common contact allergens, clinical findings of metal contact dermatitis have varied. Such patients have subsequently become rare in Japan as gold dermatitis caused by ear piercing or baboon syndrome by broken thermometers. To evaluate such clinical findings and to determine the frequency of metal allergy, we analyzed the results of patch testing with 18 metals from 1990-2009. Nine hundred and thirty-one patients (189 men and 742 women, mean age 39.0years [standard deviation±17.8]) were tested. Metals were applied on the back for 2days, and the results read with the International Contact Dermatitis Research Group (ICDRG) scoring system 3days after application. Reactions of + to +++ were regarded as positive. Differences of positive rates between men and women, and patients from 1990-1999 and those from 2000-2009 were analyzed with the χ(2) -test. Differences were considered significant at P<0.05. The metal to which the most patients reacted was 5% nickel sulfate (27.2%), irrespective of sex and phase. Significantly more women reacted to nickel sulfate (P<0.01), mercuric chloride (P<0.05) and gold chloride (P<0.01) than men. Significantly more patients in the 1990s reacted to palladium chloride, mercuric chloride and gold chloride (all P<0.01) than from 2000-2009. Nickel has been the most common metal allergen and mercury-sensitivity has decreased over 19years in Japan.

Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis: frozen-section diagnosis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may be fatal. Although classified by body surface area skin detachment, initial stages of both may present with erythema multiforme (EM)-like lesions. To diagnose and predict disease activity adequately as early as possible for patients revealing EM-like lesions, we performed frozen-section diagnosis. Thirty-five patients clinically diagnosed as EM, SJS or TEN were biopsied to diagnose and predict disease progression within the initial-visit day. Half of a histological section taken from a lesion was snap-frozen and immediately cryostat-sectioned, acetone-fixed and stained with hematoxylin-eosin. Specimens were examined with light microscopy for presence of epidermal necrosis. A section from unaffected sites was also examined for 11 patients. Specimens were examined with light microscopy for presence of graft-versus-host reaction (GVHR)-like findings: apoptotic keratinocytes and satellite cell necrosis. Epidermal necrosis was seen in nine patients. Initial diagnosis of the nine was one of overlap SJS-TEN, four of SJS and four of EM, and final diagnosis of those was one of TEN, one of overlap SJS-TEN, four of SJS and three of EM. Dissociation between initial and final diagnosis was seen in three cases. GVHR-like findings in the epidermis were observed in two patients finally diagnosed as overlap SJS-TEN and TEN. Frozen sections are useful not only to make a diagnosis of erythema multiforme but to assess a potential to exhibit more aggressive clinical behaviors (SJS or TEN).