Application of IFN‐γ releasing assay for the diagnosis of erythema induratum of Bazin

Background Erythema induratum of Bazin (EIB) is regarded to be a hypersensitive reaction to the concomitant tuberculosis. Recently, interferon‐γ releasing assay (IGRA) has been focused as a promising tool in the diagnosis of latent tuberculosis. However, there has been no large scale study to investigate the usefulness of IGRA in the diagnosis of EIB. Objectives To evaluate the diagnostic performance for the detection of EIB. Methods We retrospectively reviewed medical records of all patients with EIB, in the Department of Dermatology, at the Seoul National University Hospital, between April 2009 and September 2011. We analysed clinicopathological features, responses to IGRA and the treatment courses. In addition, we compared positive rate of IGRA in patients with other diseases during the same period. Results All of the 22 patients demonstrated a positive response to IGRA (100%) and showed a good response to anti‐tuberculosis treatment. In contrast, positive rate was 63.64% and 66.67% in patients with psoriasis and other vasculitis respectively. We observed complete resolution of skin lesions in 14 patients. Partial resolution was attained in one patient and the other seven patients are currently on the medication and are showing good responses. Conclusion We verified that IGRA has an excellent diagnostic performance in EIB, through this observational study. It is strongly suggested that if EIB is clinicopathologically suspected, IGRA should be performed.     

Erythema induratum of Bazin and Poncet''s disease – successful treatment with antitubercular drugs

Erythema induratum of Bazin (EIB) is considered a tuberculide reaction and consists of recurrent painful nodules predominantly on the calves. Clinically it has common features with diseases like nodular vasculitis, perniosis, polyarteritis nodosa and erythema nodosum. Poncet's disease is a reactive arthritis that may accompany tuberculosis. We report a case of a young woman in which the simultaneous occurrence of erythema induratum of Bazin and Poncet's disease led to a clinical picture very similar to Löfgren's syndrome. The final diagnosis was obtained by polymerase chain reaction detection of mycobacterial DNA in a skin biopsy. A systemic therapy with tuberculostatic drugs led to the disappearance of symptoms. The presented case shows the usefulness of polymerase chain reaction diagnostics in EIB patients without other clinical signs of tuberculosis and a confusing combination of symptoms, and further confirms the presence of mycobacterial DNA in EIB lesions.     

Erythema induratum of Bazin in an infant after Bacille Calmette-Guerin vaccination

We report the first case of erythema induratum of Bazin (EIB) after Bacille Calmette-Guerin (BCG) vaccination in an infant. The patient developed recurrent multiple erythematous and subcutaneous nodules on his legs 2 months after a BCG vaccination. He had no other symptoms or family history of tuberculosis (TB). Histopathological findings revealed a granulomatous lobular panniculitis. EIB often appears as a chronic, nodular eruptions that frequently occur on the lower legs of females with tuberculin hypersensitivity. To date, only a few cases of infants with EIB have been reported. There have been no clinical reports of EIB after BCG vaccination. Our case suggests that Mycobacterium bovis in the BCG vaccination may have caused EIB.     

Fas‐ligand staining in non‐drug‐ and drug‐induced maculopapular rashes

Background: Morphologically and histopathologically, drug‐ and non‐drug‐induced maculopapular rashes can be almost indistinguishable. It has been postulated that Fas‐ligand (Fas‐L) is involved in the pathogenesis of drug rashes but not in the genesis of rashes, such as viral exanthems, that are not induced by medications. Aim: This study sought to determine if epidermal Fas‐L is a distinguishing feature in the pathology of drug and non‐drug maculopapular rashes. Methods: Archived skin biopsies of patients with a confirmed diagnosis of drug or non‐drug maculopapular rashes (n = 10 each) and positive and negative controls were retrieved for immunohistochemical staining for Fas‐L. The proportion of Fas‐L‐positive skin biopsies were compared. The presence of tissue eosinophilia was also evaluated. Results: Ten percent of non‐drug‐induced rashes were Fas‐L positive compared to 50% of drug rashes (p = 0.05). Twenty percent of non‐drug exanthems had moderate tissue eosinophilia, while 60% from drug rashes had moderate to dense tissue eosinophilia (p = 0.17). Conclusion: There is a trend toward Fas‐L being more prevalent in the epidermis of drug maculopapular rashes, although this did not reach statistical significance. This is possibly because of the small sample size. Wang ECE, Lee JSS, Tan AWH, Tang MBY. Fas‐ligand staining in non‐drug‐ and drug‐induced maculopapular rashes.     

Screening for Sturge‐Weber syndrome: A state‐of‐the‐art review

Infants with a high‐risk distribution of port‐wine stains are commonly screened for Sturge‐Weber syndrome using brain magnetic resonance imaging. There is no consensus about which port‐wine stain phenotypes to screen, optimal timing, screening sensitivity, or whether presymptomatic diagnosis improves neurodevelopmental outcomes. This state‐of‐the‐art review examines the evidence in favor of screening for Sturge‐Weber syndrome, based on its effect on neurodevelopmental outcomes, against the risks and limitations of screening magnetic resonance imaging and electroencephalography. A literature search of PubMed/MEDLINE was conducted between January 2005 and May 2017 using key search terms. Relevant articles published in English were reviewed; 34 articles meeting the search criteria were analyzed according to the following outcome measures: neurodevelopmental outcome benefit of screening, diagnostic yield, financial costs, procedural risks, and limitations of screening magnetic resonance imaging and electroencephalography. There is no evidence that a presymptomatic Sturge‐Weber syndrome diagnosis with magnetic resonance imaging results in better neurodevelopmental outcomes. The utility of electroencephalographic screening is also unestablished. In Sturge‐Weber syndrome, neurodevelopmental outcomes depend on prompt recognition of neurologic red flags and early seizure control. Small numbers and a lack of prospective randomized controlled trials limit these findings. For infants with port‐wine stain involving skin derived from the frontonasal placode (forehead and hemifacial phenotypes), we recommend early referral to a pediatric neurologist for parental education, counselling, and monitoring for neurologic red flags and seizures and consideration of electroencephalography regardless of whether magnetic resonance imaging is performed or its findings.     

In vitro and in vivo evidence of tyrosinase inhibitory activity of a synthesized (Z)‐5‐(3‐hydroxy‐4‐methoxybenzylidene)‐2‐thioxothiazolidin‐4‐one (5‐HMT)

Tyrosinase is a key enzyme that catalyses the initial rate‐limiting steps of melanin synthesis. Due to its critical role in melanogenesis, various attempts were made to find potent tyrosinase inhibitors although many were not safe and effective in vivo. We evaluated tyrosinase inhibitory activity of six compounds. Among them, (Z)‐5‐(3‐hydroxy‐4‐methoxybenzylidene)‐2‐thioxothiazolidin‐4‐one (5‐HMT) had the greatest inhibitory effect and potency as the IC₅₀ value of 5‐HMT was lower than that of kojic acid, widely‐known tyrosinase inhibitor. Based on in silico docking simulation, 5‐HMT had a greater binding affinity than kojic acid with a different binding conformation in the tyrosinase catalytic site. Furthermore, its skin depigmentation effect was confirmed in vivo as 5‐HMT topical treatment significantly reduced UVB‐induced melanogenesis in HRM2 hairless mice. In conclusion, our study demonstrated that 5‐HMT has a greater binding affinity and inhibitory effect on tyrosinase and may be a potential candidate for a therapeutic agent for preventing melanogenesis.     

Docetaxel‐induced photo‐recall phenomenon

Photo‐recall phenomenon is a phototoxic eruption occurring on areas of previous ultraviolet‐induced solar erythema following a systemic administration of a drug. It has been mostly described with methotrexate but remains rare with other antineoplastic drugs. We describe a case of docetaxel‐induced photo‐recall skin rash in a woman treated for a non‐small‐cell lung cancer. Although the patient has refused to receive a second infusion, chemotherapy can be carried on with photoprotection and the use of topical and/or systemic corticosteroids. In contrast, radiation recall is a well‐known reaction by oncologists, most of them may not be aware of a similar phenomenon called photo‐recall phenomenon. Recognizing this entity may avoid misdiagnosing a drug allergy and should avoid inappropriate decisions of drug discontinuation.     

High‐fat diet exacerbates imiquimod‐induced psoriasis‐like dermatitis in mice

Psoriasis, a chronic inflammatory skin disease, is closely related to systemic metabolism. An elevated body mass index (BMI) is a risk factor for psoriasis; inflammasomes are activated by adipose tissue macrophages in obese subjects. We hypothesized that hyperlipidaemia is involved in the pathogenesis of psoriasis and examined the role of a high‐fat diet (HFD) in the development of psoriasis in imiquimod (IMQ)‐treated mice. The body weight and serum level of cholesterol were significantly higher in mice fed an HFD than in a regular diet (RD). HFD mice had higher psoriasis skin scores, and the number of neutrophils infiltrating into the lesional skin was elevated. IL‐17A mRNA expression was significantly increased in the skin of IMQ‐treated HFD mice; the expression of IL‐22, IL‐23 and TNF‐α mRNA was not enhanced. Caspase‐1 and IL‐1β were activated in the skin of IMQ‐treated HFD mice, and their serum level of IL‐17A, TNF‐α and IL‐1β was significantly upregulated. Our findings strongly suggest that hyperlipidaemia is involved in the development and progression of psoriasis via systemic inflammation and inflammasome activation.     

Case of thymoma‐associated cutaneous graft‐versus‐host disease‐like disease successfully improved by narrowband ultraviolet B phototherapy

Thymoma‐associated graft‐versus‐host disease (GVHD)‐like disease is a rare paraneoplastic disease seen in patients with thymoma. Here, we describe the first case of thymoma‐associated GVHD‐like disease localized to the skin that was successfully improved by a combination of systemic corticosteroids and whole‐body narrowband ultraviolet (UV)‐B phototherapy. The patient had developed toxic epidermal necrolysis‐like erosive skin lesions over the whole body. Although systemic corticosteroids were effective up to a point, we were unable to begin the steroid taper. The addition of systemic narrowband UV‐B phototherapy improved the skin manifestation of this disease, allowing corticosteroids to be reduced to a third of the original dose. Histopathologically, it was confirmed that the proportion of Foxp3‐positive lymphocytes in the skin increased after narrowband UV‐B irradiation. We propose that whole‐body narrowband UV‐B phototherapy is a good therapeutic option for the skin manifestation of thymoma‐associated GVHD‐like disease.     

Cross‐elicitation responses to 2‐methoxymethyl‐p‐phenylenediamine in p‐phenylenediamine‐allergic individuals: Results from open use testing and diagnostic patch testing

Background

Allergic contact dermatitis caused by p‐phenylenediamine (PPD) is a health concern for hair dye users. Because of its lower sensitization potency, the PPD derivative 2‐methoxymethyl‐p‐phenylenediamine (ME‐PPD) has been developed as an alternative hair dye for primary prevention. However, cross‐elicitation responses can occur in PPD‐allergic subjects.

Objectives

To compare cross‐elicitation responses to ME‐PPD in open use and diagnostic patch testing of PPD‐allergic subjects with hair dye‐related allergic contact dermatitis.

Methods

Reactions to ME‐PPD were investigated in 25 PPD‐allergic subjects by performing (1) 45‐minute open use testing with a hair dye containing 2.0% of either ME‐PPD or PPD, and (2) patch testing with increasing ME‐PPD concentrations (0.1%–2.0% pet.).

Results

Of the 25 PPD‐allergic subjects, 21 (84%) reacted to open use testing with a hair dye containing 2.0% PPD, and testing with 2.0% ME‐PPD led to cross‐elicitation in 12 (48%). When patch tested with increasing ME‐PPD concentrations, 13 (52%) cross‐reacted at 0.1% (lowest dose) and 21 (84%) at 2.0% (highest dose), indicating decreased reactivity as compared with published PPD dose‐response data.

Conclusion

In line with the decreased cross‐reactivity of ME‐PPD in hair dye open use testing, PPD‐allergic subjects show an attenuated cross‐elicitation dose response to ME‐PPD in patch testing.     

Acro‐Dermato‐Ungual‐Lacrimal‐Tooth Syndrome: An Uncommon Member of the Ectodermal Dysplasias

Acro‐dermato‐ungual‐lacrimal‐tooth (ADULT) syndrome is a rare form of autosomal dominant ectodermal dysplasia due to mutations in the TP63 gene, a locus that has also been implicated in other syndromic forms of ectodermal dysplasia. It shares many phenotypic characteristics with other TP63 gene mutation syndromes, often making an accurate diagnosis difficult. Long‐term management and follow‐up of the various sequelae of ectodermal dysplasia require an accurate diagnosis. We report a familial case of ADULT syndrome in a daughter, mother, and son and provide a brief review of the clinical characteristics of this syndrome.     

Allergic Contact Dermatitis Caused by P‐Tert‐Butylphenol‐Formaldehyde Resin in Orthopedic Braces

P‐tert‐butylphenol‐formaldehyde resin is a widely used adhesive chemical. It is used in a broad range of products and should be kept in mind when encountering children with suspected allergic contact dermatitis. We present a girl who developed contact allergy to p‐tert‐butylphenol‐formaldehyde resin used in orthopedic braces.     

Reduction in the appearance of facial hyperpigmentation by topical N‐undecyl‐10‐enoyl‐l‐phenylalanine and its combination with niacinamide

Objectives N‐undecyl‐10‐enoyl‐l ‐phenylalanine (Sepiwhite^®, N‐undecylenoyl phenylalanine), a reported alpha‐melanocyte‐stimulating hormone (MSH) receptor antagonist, has been observed to reduce melanin production in cultured melanocytes. In other testing, niacinamide has been found to inhibit melanosome transfer in cultured cells and to reduce the appearance of hyperpigmented spots in clinical studies. Since these two agents function by different mechanisms, we conducted two studies to determine if their combination is more effective than niacinamide alone in reducing facial hyperpigmentation. Methods  Two double‐blind, 10‐week (2‐week washout + 8‐week treatment), left‐right randomized, split‐face clinical studies were conducted. In one, two groups of Japanese women applied one of two pairs of test emulsion formulations: a vehicle control and a 5% niacinamide formulation (n= 40), or a 5% niacinamide and a 5% niacinamide plus 1%N‐undecylenoyl phenylalanine formulation (n = 40). Each formulation was applied to the randomly assigned side of the face. In the second study, Caucasian women applied one of three emulsions: vehicle control, 5% niacinamide formulation, or combination 5% niacinamide plus 1%N‐undecylenoyl‐phenylalanine formulation to the randomly assigned side of the face (n = ～60 treatment sites per formulation). In both studies, hyperpigmented spots were evaluated at weeks 4 and 8 by quantitative image analysis. Results  In both studies, the combination formulation was significantly more effective than the vehicle and the 5% niacinamide formulation in reducing the appearance of hyperpigmentation after 8 weeks. Conclusions  The combination of 5% niacinamide and 1%N‐undecylenoyl phenylalanine is an effective anti‐aging technology for use on facial skin.     

Endothelial chimerism in chronic sclerotic‐type chronic graft‐versus‐host disease (GVHD) and GVHD‐associated angiomatosis

Graft‐versus‐host disease‐associated angiomatosis (GVHD‐AA) is an uncommon manifestation of chronic GVHD consisting of friable vascular proliferations. Using fluorescence in situ hybridization, we demonstrate the presence of donor‐derived endothelial cells within areas of GVHD‐AA. This is the first documented occurrence of a benign neoplastic growth in relationship to a form of chronic GVHD.     

Geriatric teledermatology: store‐and‐forward vs. face‐to‐face examination

Background Telemedicine could be useful in countries like Italy to meet the needs of elderly patients and in particular in those in precarious general conditions, for whom travelling even short distances can pose considerable practical and economical difficulties. Objective The aim of this study was to determine the efficacy of store‐and‐forward teledermatology vs face‐to‐face consultations in elderly patients. Methods A total of 130 geriatric patients with skin diseases requiring dermatological examination were enrolled. The patients examined, consisting of 60 men (46.15%) and 70 women (53.85%), were aged between 66 and 97 years (mean age 80.58 years). Three dermatologists of the department, with equal experience took turns in face‐to‐face examination and teledermatology (store‐and‐forward). To compare face‐to‐face dermatological examinations with the asynchronous store‐and‐forward approach of teledermatology, we considered diagnostic agreement (ICD‐9 code), therapeutic agreement and concordance of diagnostic confidence. Results One hundred and fourteen of 130 patients were diagnosed with the same ICD‐9 code, making a total observed agreement of 87.7% with a Cohen’s κ estimated of 0.863. Agreement between therapies was 69.6% (Cohen’s κ = 0.640). As it concerns diagnostic confidence, dermatologists appeared generally slightly less certain of their diagnosis by telemedicine. Conclusions Store‐and‐forward teledermatology can improve diagnostic and therapeutic care for skin disease in elderly who lack easy and/or direct access to dermatologists.     

I‐Ascorbic acid 2‐phosphate represses the dihydrotestosterone‐induced dickkopf‐1 expression in human balding dermal papilla cells

Abstract: Recent studies suggested that dihydrotestosterone (DHT)‐driven alteration in the autocrine and paracrine factors may be a key to androgen‐potentiated balding. Also, we recently claimed that DHT‐inducible dickkopf‐1 (DKK‐1) is one of the key factors involved in the androgen‐potentiated balding. Here, we investigated whether I‐ascorbic acid 2‐phosphate (Asc 2‐P), a derivative of I‐ascorbic acid, could attenuate DHT‐induced DKK‐1 expression in dermal papilla cells (DPCs) from balding scalp. We observed that DHT‐induced DKK‐1 mRNA expression was attenuated in the presence of Asc 2‐P as examined by RT‐PCR analysis. In addition, we found that DHT‐induced activation of luciferase reporter activity was significantly repressed when Asc 2‐P was added together with DHT. Moreover, Asc 2‐P repressed DHT‐induced DKK‐1 protein expression as examined by enzyme‐linked immunosorbent assay (ELISA). Although there will be many hurdles to apply our finding to actual remedies, these results suggest that it would be worthy to evaluate Asc 2‐P or its derivatives for the treatment and prevention of androgen‐driven balding.     

Skin‐penetrating methotrexate alleviates imiquimod‐induced psoriasiform dermatitis via decreasing IL‐17‐producing gamma delta T cells

Accumulating evidence has shown that the Toll‐like receptor 7 agonist imiquimod (IMQ) induces psoriasiform skin inflammation in mice and that this inflammation is dependent on the IL‐23/IL‐17 axis. Moreover, it has been demonstrated that the main source of IL‐17 is not Th17 but is dermal gamma delta (γδ) T cells in mouse psoriasiform skin. Recent advances in the understanding of immunopathogenesis of psoriasis led to an alteration in the treatment paradigm to the use of highly efficacious biologics. However, their high cost impedes the extensive use of these agents. Thus, inexpensive and safe medications are still considered valuable. In this study, we introduce the therapeutic efficacy of a newly formulated methotrexate (MTX), a chemical conjugate of MTX with cell permeable peptide, for the treatment of psoriasis. Topically applied skin‐penetrating (SP)‐MTX reduced the psoriasiform skin phenomenon, epidermal thickness and infiltrating immune cells into the dermis. IL‐17A‐producing dermal γδ T cells in the cellular infiltrate that contribute IL‐23/IL‐17 axis were well abrogated by SP‐MTX. Furthermore, SP‐MTX had no toxic effects on liver, kidney or myeloid cells, unlike systemic administration of MTX. In conclusion, topically applied SP‐MTX ameliorated psoriasiform skin inflammation in mice with the criteria of clinical phenomenon, histopathology and immunology, without inducing systemic toxic effects.     

Anti‐Laminin‐332 Mucous Membrane Pemphigoid in a 9‐Year Old Girl

Mucous membrane pemphigoid (MMP), an autoimmune subepithelial blistering disease that predominantly affects the mucous membranes, is usually diagnosed in elderly adults. Early diagnosis of MMP is crucial because it tends to run a chronic and progressive course with the potential for devastating scarring of the mucous membranes that may lead to blindness and airway compromise. A subtype of MMP, anti‐laminin‐332 MMP, is a rare blistering disorder in which autoantibodies are directed against laminin‐332 (formerly epiligrin), a structural protein of the epidermal basement membrane. Herein we report what we believe to be the youngest patient diagnosed with anti‐laminin‐332 MMP, a 9‐year‐old girl with disease affecting only the oral, pharyngeal, and laryngeal mucosa, with no skin involvement.     

Congenital plaque‐like glomangioma treated successfully with dual wavelength pulsed‐dye and neodymium:yttrium‐aluminum‐garnet laser

Glomovenous malformations are disseminated variants of cutaneous glomus tumors. These malformations are subdivided into regional or localized, disseminated, and congenital plaque‐like forms. The congenital plaque‐like form is the rarest variant. Most treatment modalities have been disappointing in the treatment of large glomangiomas, leading to high recurrence rates. We report a case of a 34‐year‐old man with a congenital plaque‐like glomangioma on his left arm and forearm treated successfully with sequential pulsed‐dye neodymium yttrium aluminum garnet laser.