K. Muramatsu

Two cases of erosive oral lichen planus with autoantibodies to desmoglein 3.

Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa of unknown etiology. Clinically, the erosive type of OLP (erosive OLP) can show features similar to those of pemphigus vulgaris (PV), an autoimmune blistering disorder in which desmoglein (Dsg)3 is targeted. In addition to clinical and histopathological findings, immunological studies, including direct immunofluorescence (IF), indirect IF and enzyme‐linked immunosorbent assay (ELISA) that detect autoantibodies to Dsg3, are helpful in differentiating erosive OLP from PV. Here, we show two cases of erosive OLP with autoantibodies to Dsg3. Patient 1 was a 68‐year‐old woman with chronic erosions of the oral mucosa, in which elevated levels of immunoglobulin (Ig)G autoantibodies to Dsg1 and Dsg3 were detected by ELISA. Patient 2 was an 85‐year‐old woman with white striae with erosions on the lateral sides of the buccal mucosa with elevated levels of IgG autoantibodies to Dsg3 detected by ELISA. Histopathological findings from both cases showed lichenoid dermatitis, and both direct and indirect IF showed no tissue‐bound IgG autoantibodies. From these findings, the diagnosis of erosive OLP was made. Immunological assays revealed both cases to have IgG‐directing calcium‐independent linear epitopes on Dsg3, which are suggestive of non‐pathogenic autoantibodies. In addition, autoantibodies to Dsg3 in patient 2 reacted with a prosequence‐possessing precursor form of Dsg3 but not with the mature form of the molecule. The present study suggests that erosive OLP may develop anti‐Dsg3 autoantibodies, which should be carefully assessed.

A severe case of X-linked ichthyosis showing palmar hyperlinearity without FLG mutations.

Editor A 57-year-old Japanese man was referred to us with generalised dry skin and dark brown, adherent scales on the trunk and extremities (Fig. 1a). Plate-like scales were also noted on the shins (Fig. 1b). His cutaneous manifestations had been present since soon after birth. He had a past medical history of squamous cell carcinoma of the gingiva, but was otherwise healthy. His unrelated parents and four sisters were all unaffected. Moreover, none of the male members in the maternal family were affected. A skin biopsy showed compact hyperkeratosis and basal melanosis without parakeratosis and/or acanthosis. Stratum granulosum was neither thickened nor diminished. From these findings, he was suspected of having X-linked ichthyosis (XLI). After obtaining approval for genetic study from the institutional review board and written informed consent from the patient, we performed fluorescence in situ hybridization using his white blood cells, which detected a genomic deletion at the STS locus on Xp22.3 (data not shown); this confirmed the diagnosis of XLI. Notably, he also manifested palmar and plantar hyperlinearity, with the former much more pronounced (Fig. 1c). Taken together with his severe skin conditions for XLI, this led us to suspect an additional mutation in the gene encoding filaggrin (FLG). We performed mutation analysis of the entire coding regions of FLG using the genomic DNA extracted from his peripheral blood as described previously; however, it identified no loss-of-function mutations. Our patient showed severe skin phenotypes for XLI. Liao et al. reported an association between FLG mutations and exacerbation of XLI phenotypes. In their study, two affected brothers showed different phenotypic severity, despite having a same STS genomic deletion. Notably, the more severely affected brother was found to be a heterozygous carrier of the nonsense mutation p.Arg501Ter in FLG, whereas the other was wild-type for the mutation. These findings, together with the fact that about 10% of the Japanese and British populations have loss-offunction mutations in FLG, indicate that FLG mutations can modify or exacerbate phenotypes of genodermatoses including XLI. However, our patient with XLI presented severe phenotypes without FLG mutations. Interestingly, Gruber et al. reported an XLI family in which two affected brothers carrying pathogenic mutations both in STS and FLG presented strikingly variable phenotypic severity, which indicates that hitherto unrecognised genes might contribute to phenotypic severity in XLI. This study provides further evidence for genetic and/or environmental modifiers exacerbating XLI other than FLG mutations. Palmar hyperlinearity is widely accepted as a useful clinical finding for the differential diagnosis of XLI and ichthyosis vulgaris (IV) because it has been reported to be specific to IV and/ or atopic dermatitis (AD). Nevertheless, our XLI patient showed palmar hyperlinearity without FLG mutations. CuevasCovarrubias et al. also reported a case of XLI presenting with palmar hyperlinearity with clinical signs of neither IV nor AD, although mutation analysis of FLG was not performed in their patient. These findings suggest that patients with XLI might exhibit palmar hyperlinearity even without FLG mutationrelated disorders, although a larger case study is warranted to validate this hypothesis.

Thymoma-associated multi-organ autoimmunity: two cases and a review of the literature.

Thymoma-associated multi-organ autoimmunity (TAMA) is defined as a disease of the liver, intestine, and skin, which histopathologically resembles graft-versus-host disease (GVHD).1,2 Several sporadic cases imply that cutaneous manifestations of TAMA are associated with a poor prognosis.2-5 However, it is difficult to examine the association because of the rarity of the disease. Herein we describe two cases of TAMA with cutaneous lesions and fatal courses, and review the literature with a focus on the prognosis. This article is protected by copyright. All rights reserved.

Repeated skin sampling and prolonged incubation period identified cutaneous Mycobacterium chelonae infection on the face in an immunocompetent man

1 Zuberbier T, Asero R, Bindslev-Jensen C, et al. EAACI/GA(2)LEN/ EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy 2009; 64:1417–26. 2 Zuberbier T, Asero R, Bindslev-Jensen C, et al. EAACI/GA(2)LEN/ EDF/WAO guideline: management of urticaria. Allergy 2009; 64:1427–43. 3 Kaplan A, Ledford D, Ashby M, et al. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol 2013; 132:101–9. 4 Maurer M, Ros en K, Hsie HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. New Engl J Med 2013; 368:924–35. 5 Metz M, Altrichter S, Ardelean E, et al. Anti-immunoglobulin E treatment of patients with recalcitrant physical urticaria. Int Arch Allergy Immunol 2011; 154:177–80. 6 Magerl M, Borzova E, Gim enez-Arnau A, et al. The definition and diagnostic testing of physical and cholinergic urticarias – EAACI/ GA2LEN/EDF/UNEV consensus panel recommendations. Allergy 2009; 64:1715–21. 7 Altrichter S, Peter HJ, Pisarevskaja D, et al. IgE mediated autoallergy against thyroid peroxidase – a novel pathomechanism of chronic spontaneous urticaria? PLoS ONE 2011; 6:e14794. 8 Maurer M, Altrichter S, Bieber T, et al. Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyreoperoxidase. J Allergy Clin Immunol 2011; 128:202–9.

Regulatory T-cell dysfunction induces autoantibodies to bullous pemphigoid antigens in mice and human subjects

Background: Regulatory T (Treg) cells play a crucial role in peripheral immune tolerance in multiple organs, including the skin. Thus far, the effect of peripheral immune tolerance failure on autoantibody‐related autoimmune reactions to the skin is unclear. Objective: We sought to elucidate the target autoantigens in the skin under the condition of Treg cell dysfunction caused by forkhead box P3 (Foxp3) gene mutations in scurfy mice and patients with immunodysregulation, polyendocrinopathy, enteropathy, X‐linked (IPEX) syndrome. Methods: Sera and skin from scurfy mice and sera from patients with IPEX syndrome were analyzed to detect target autoantigens by using immunofluorescence studies, ELISAs, and immunoblotting. The pathogenicity of scurfy IgG was examined by using a passive transfer experiment. CD4+ T cells from scurfy mice were transferred to immunodeficient mice to examine their pathogenicity. Signal transducer and activator of transcription 6 (Stat6)−/− scurfy mice were analyzed to further clarify the molecular pathway of autoantibody production. Follicular helper T‐cell counts are measured in Stat6−/− scurfy mice and scurfy mice. Results: Scurfy mice spontaneously generated IgG autoantibodies to the dermal‐epidermal junction, which had been class‐switched from IgM within 12 days after birth. The target autoantigens were murine BP230 and type XVII collagen (COL17). The scurfy polyclonal autoantibodies did not induce skin fragility in neonatal mice. Autoantibody production was induced by CD4+ T cells from scurfy mice and was ameliorated by Stat6 gene knockout in association with a decrease of follicular helper T cells. We also identified autoantibodies to COL17 and BP230 in patients with IPEX syndrome and found an association between production of autoantibodies to COL17 and an eczematous skin phenotype. Conclusions: Dysregulation of Treg cells generates autoantibodies to COL17 and BP230 in vivo. GRAPHICAL ABSTRACT Figure. No caption available.

A possible association between BP230-type bullous pemphigoid and dementia: a report of two cases in elderly patients

Bullous pemphigoid (BP) is the most common autoimmune blistering disease, and it features itchy oedematous erythemas and tense bullae on the whole body most commonly in the elderly. BP180 is the most common autoantigens of BP, and BP230 is the only target of autoantibodies in approximately 8% of patients with BP1 . It has been reported that elderly patients with BP sometimes have comorbidities associated with neurological disease (ND) including dementia2 . BP antigens and their isoforms can be identified in skin as well as in neuronal tissues, suggesting that exposure of the neuronal antigen may lead to an immune reaction against the epithelial isoform3 . Here, we describe two elderly cases of BP with dementia in which the autoantibodies reacted to BP230 but not to BP180 (BP230-BP). This article is protected by copyright. All rights reserved.

Maculopapular drug eruption induced by linagliptin

of other non-scarring alopecia in women. Shedding and hair density improved in an even pattern within 3 months. The response to the treatment resulted in a change in hair colour from reddish-brown to light brown (Fig. 2). The patient did not dye her hair. Oral minoxidil was ceased after 12 months when hair density and length was normal for her age, with a half-dose reduction every 2 weeks. There has been no recurrence of loose anagen hair syndrome after the cessation of minoxidil after 12 months of follow up. The possible mechanisms of action of minoxidil in loose anagen hair syndrome include increased local cutaneous blood flow, prolonged keratinocyte lifespan, increased cell proliferation and DNA synthesis in the follicular and perifollicular keratinocytes. A recent case report suggests that the increase in DNA synthesis and cell proliferation by topical minoxidil modifies the disordered keratinization of the inner root sheath and improves hair anchorage. Our experience of treating non-scarring alopecias with topical and systemic minoxidil in older children (e.g. 12years old) has been generally favourable, with very few patients experiencing intolerable adverse effects. In this case, change in hair colour was used as a clinical indicator of response to treatment. We believe that a change in hair colour can be an indicator of disease resolution; however the mechanism of colour change is unclear.

Lichenoid drug eruption caused by clonazepam

ment. Drug-induced CCLE and the lupus tumidus variant are very rarely reported; the former has been related mainly to fluorouracile, TNF-alpha inhibitors and anti-inflammatory drugs, while the latter (just five cases of lupus tumidus published so far) has been linked to bortezomib, ACE-inhibitors and TNFalpha inhibitors as well. CCLE is a clinical entity characterized by classic discoid skin lesions with a photosensitive distribution on the face, upper trunk and arms, lacking of systemic manifestations. The laboratory panel includes a positivity of ANA in 66% of the cases, while anti-ENA, anti-dsDNA and anti-histone antibodies are usually absent. The onset of CCLE lesions ranges from 1 week to 8 months after drug exposure; the symptoms tend to resolve within a few months after drug withdrawal, with a parallel slower decrease in ANA titres. The temporal relationship in our case mirrors previously reported CCLE cases, although its resolution was slower compared to cases of CCLE induced by TNF-alpha inhibitors. This could be due to the absence, in our patient, of any other systemic treatment (as hydroxychloroquine and steroids) and to different underlying pathogenetic mechanisms, as TNF-alpha inhibitors for instance are known for their higher immunogenicity. As a matter of fact, the pathogenesis of DIL both systemic, subacute and chronic is unclear, but our case reinforces the hypothesis that specific drug classes are likely to evoke individual autoimmune mechanisms probably in the presence of genetic factors. The prognosis of DIL is usually good; hence, it is important to distinguish it from the relative idiopathic forms. In conclusion, our report of a CCLE induced by methimazole draws attention on this potential cutaneous side-effect. Although seemingly rare and milder than systemic DIL, it can worsen the quality of life and dermatologists should be aware of this condition associated to methimazole therapy.

Recurrence of juvenile dermatomyositis 8 years after remission

CDASI: Cutaneous Dermatomyositis Area and Severity Index JDM: juvenile dermatomyositis MTX: methotrexate mPSL: methylprednisolone PSL: prednisolone INTRODUCTION Juvenile dermatomyositis (JDM) is a chronic inflammatory disease characterized by typical skin lesions and muscle weakness, which occurs in children and adolescents younger than 16 years. JDM is classified into 3 clinical types according to the posttreatment course: (1) monocyclic, in which there is one episode with permanent remission within 2 years after diagnosis; (2) polycyclic, with multiple relapses within 2 years; and (3) continuous, with pathologic states persisting for more than 2 years. Early treatment with prednisolone is suggested to limit the disorder to the monocyclic course. Only 2 case reports in which monocyclic JDM recurred more than 3 years after remission have been described in the English-language literature. Of these 2 reported cases, 1 patient had no initial treatment and the other had oral prednisolone (PSL) alone. Recently a well-designed randomized, controlled trial found that aggressive therapeutic approaches, such as PSL plus methotrexate (MTX) after methylprednisolone (mPSL) pulse therapy, outperform PSL monotherapy after mPSL pulse therapy with respect to clinical remission, treatment failure, and discontinuation of PSL. Here we present a case of monocyclic JDM that recurred 8 years after remission despite initial treatment with PSL plus MTX after mPSL pulse therapy.

Postherpetic abdominal pseudohernia

A 46 year old man presented with a 2 week history of protrusion of the right abdominal wall. He had suffered from herpes zoster in …