Azathioprine‐induced Sweet's syndrome and published work review

Hypersensitivity to azathioprine can manifest with a wide clinical spectrum. Azathioprine‐induced Sweet's syndrome (SS) is rare and usually overlooked because it can mimic disease exacerbation and sepsis. This study aims to characterize the clinical findings of azathioprine‐induced SS. A retrospective analysis of the records of three patients diagnosed with azathioprine‐induced SS and a review of the relevant English‐language published work was performed. Twelve (71%) of the 17 patients were male, ranging 9–89 years in age (mean, 47.2). The time of onset after starting azathioprine was 5–28 days (mean, 13.3). The most common associated disease was inflammatory bowel disease including ulcerative colitis and Crohn's disease (76%). The clinical features typically consisted of fever and classic rash of SS with pustules and vesicles. The lesions occurred most commonly on the face and trunk. Systemic involvement was rare and no hypotension or shock was reported as seen in azathioprine hypersensitivity syndrome. Thiopurine methyltransferase activity is not predictive of this type of adverse effect. Most patients dramatically responded to systemic corticosteroids. Azathioprine‐induced SS may be underdiagnosed because it can be easily misinterpreted as inflammatory bowel disease‐associated skin eruption. Patients with inflammatory bowel disease may be at higher risk of this condition. Early recognition and drug withdrawal can decrease morbidity of the patients.     

Triggering factors in sensitive skin from the worldwide patients’ point of view: a systematic literature review and meta-analysis

Sensitive skin (SS) is a syndrome defined by the occurrence of unpleasant sensations in response to stimuli that normally should not provoke such sensations. In most patients, symptoms occur within 1 h following exposure to trigger factors and may persist for minutes or even hours. Numerous triggering factors (physical, chemical or psychological) are suspected and described in articles. The aim of this article was to perform a systematic literature review to collect data on the triggering factors involved in SS and to then perform a meta-analysis. Thirteen studies were included in the systematic literature review. Subjects were classified into groups, SS or no sensitive skin (NSS), and triggering factors were researched through responses to different questions. SS could be triggered by numerous factors. The most important triggering factor was cosmetics, with an odds ratio (OR) equal to 7.12 [3.98–12.72]. Other triggering factors were physical (variations in temperature, cold, heat, wind, sun, air conditioning, wet air and dry air), chemical (water and pollution) or psychological (emotional) factors. After cosmetics, the most important factors were wet air, OR 3.83 [2.48–5.91]; air conditioning, OR 3.60 [2.11–6.14]; heat, OR 3.5 [2.69–4.63]; and water, OR 3.46 [2.56–4.77].     

Longitudinal observational study of hidradenitis suppurativa: impact of surgical intervention with adjunctive biologic therapy

Background

Hidradenitis supppurativa (HS) is a chronic inflammatory disease of the apocrine sweat glands affecting 1–4% of the population. While surgical excision is a mainstay of therapy, lesions often recur. Biologic therapies, including tumor necrosis factor‐α and IL‐12/23 inhibitors, are effective for mild to moderate HS. However, longitudinal studies investigating biologic therapy in conjunction with surgery are limited. The purpose of this analysis was to investigate impact of surgery and biologic therapy on HS disease activity.

Methods

Data from 68 HS patients were analyzed. Outcome measures included hidradenitis suppurativa Sartorius Score (HSS), active nodule (AN) count, Hurley stage, and probability of achieving 75% reduction in active nodule count (AN75).

Results

Mean age was 40 ± 14 years; 66% were female and 72% were African American. Mean disease duration was 10 years, and Hurley stage III disease was seen in 63% of patients. Patients who received biologics had a larger drop in HSS and AN count than those who never received biologics (P = 0.002). Biologic treatment was associated with average reduction in 22 (15–29) HSS points (P < 0.0001). The effect of biologics was greater in patients who also underwent surgery (P = 0.013). Timing of biologics relative to surgery did not impact efficacy. Patients who received HS surgery with biologic therapy were most likely to achieve the AN75 (P = 0.017).

Conclusions

In this diverse cohort of patients with severe HS, biologic therapy was associated with a more rapid decline in disease activity, with the greatest effect in patients who also underwent HS surgery.     

Analysis of 303 Ro/SS‐A antibody‐positive patients: is this antibody a possible marker for malignancy?

Background The risk of cancer in patients with autoimmune diseases has been investigated in several studies. Ro/SS‐A antibodies are frequent and specific autoantibodies among patients with various autoimmune diseases. Objectives To assess the risk of cancer in individuals with positive Ro/SS‐A antibodies and to analyse their clinical and laboratory characteristics. Methods Consecutive patients (n = 303) with Ro/SS‐A antibody positivity were collected during 11 years in our outpatient clinic for autoimmune diseases and were retrospectively analysed. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all cancers were calculated. In addition, we identified further clinical and laboratory characteristics of Ro/SS‐A antibody‐positive patients indicating the development or existence of a malignancy. Results Fifty (16·5%) patients were diagnosed with malignancies. Ro/SS‐A antibody was strongly associated with malignant diseases (SIR 2·6, 95% CI 1·9–6·1), particularly melanoma (SIR 33·3, 95% CI 5·2–188·6), T‐cell lymphoma (SIR 16·7, 95% CI 2·9–128·9), non‐Hodgkin lymphoma (SIR 10·6, 95% CI 1·5–78·9) and breast carcinoma (SIR 4·98, 95% CI 1·3–28·3). Logistic regression modelling revealed that Ro/SS‐A antibody‐positive patients aged 55 years or older, presenting with fever, anaemia and cutaneous lupus erythematosus, have a greater probability of developing cancer and are considered high‐risk patients, as compared with Ro/SS‐A antibody‐positive patients with none of the mentioned clinical criteria. Conclusions In our cohort of Ro/SS‐A antibody‐positive patients, an overall increased risk of malignancy was noticed. Regular screening tests including imaging and laboratory values are justified in Ro/SS‐A antibody‐positive patients who exhibit the mentioned clinical criteria.     

Benign neonatal hemangiomatosis with early regression of skin lesions: A case report and review of the published work

A 2-day-old Japanese male infant was referred to our outpatient clinic for multiple cutaneous hemangiomas present since birth. Physical examination revealed 14 small, well-circumscribed red papules, scattered over the head, face, dorsum of the right hand, trunk, lower extremities, buttocks and penis. Ultrasound examination revealed no evidence of visceral involvement. Histological examination of a cutaneous lesion was consistent with infantile hemangioma, resulting in the final diagnosis of benign neonatal hemangiomatosis (BNH). The hemangiomas enlarged by 1 month of age and began to resolve at 2 months of age. Within the next month, the lesions had almost completely disappeared. BNH is a rare, non-heritable, self-limited, benign disease characterized by multiple cutaneous infantile hemangiomas and no or unremarkable visceral lesions. Generally, BNH lesions spontaneously regress within the first 1–2 years of life or within 4 months of onset. However, there have been no detailed reports about the time course of BNH. To our knowledge, 31 cases of BNH without hepatic hemangiomas, excluding this case, have been reported so far. Twenty-one of these cases demonstrated spontaneous regression of the cutaneous hemangiomas without treatment. In all cases, the cutaneous hemangiomas were present at birth. The median age at the beginning of spontaneous regression was 6.0 months (range, 1–12) and the median age at complete or almost complete regression was 15 months (range, 3–28). Cutaneous hemangiomas in BNH without hepatic hemangiomas undergo spontaneous regression within the first year of life.     

Assessment of nailfold capillaroscopy by x 30 digital epiluminescence (dermoscopy) in patients with Raynaud phenomenon

Background Dermoscopy is a useful tool for dermatologists to study melanocytic lesions. Its possible usefulness in the assessment of capillary nailfold morphological changes (capillaroscopy) has recently been advocated. Objectives To assess the practical utility of digital epiluminescence microscopy as a capillaroscopic instrument in patients with Raynaud phenomenon (RP). To compare the sensitivity and specificity rates obtained by epiluminescence microscopy with those previously reported with conventional capillaroscopic devices. Methods Fifty‐six consecutive patients with primary RP (PRP; n = 5) or secondary RP (SRP; n = 51) (11 men and 45 women in total) were included in the study. A control group of 10 healthy subjects was also evaluated. Twenty‐six patients (46%) had systemic sclerosis (SS), 12 (21%) presystemic sclerosis (pre‐SS), one (2%) dermatopolymyositis–SS, one (2%) mixed connective tissue disease, two (4%) Sjögren syndrome, two (4%) an overlap syndrome, one (2%) rheumatoid arthritis and six (11%) other connective tissue diseases. Capillary nailfold changes were studied using a nonportable digital epiluminescence device (magnification × 30). Following a systematized protocol, capillary nailfold morphology, density and distribution were evaluated. Several capillaroscopic patterns were identified (normal, sclerodermic, nonspecific, nondiagnostic) as previously defined. A possible relationship between capillary nailfold changes and the intensity of RP or the presence of associated autoimmune diseases was assessed. Results The sclerodermic pattern showed a sensitivity of 76·9% and a specificity of 90·9% in SS. A typical capillaroscopic SS pattern was observed in 73% of cases of limited SS and in 82% of cases of diffuse SS. Patients with Sjögren syndrome and dermatopolymyositis–SS showed a nonspecific capillaroscopic pattern. All patients with PRP presented a normal capillaroscopic pattern. A normal capillaroscopic pattern was also observed in 11 of 12 patients with pre‐SS. In one of two patients presenting severe sclerodactyly and in all patients showing hand oedema (three of 56), capillaroscopic changes could not be evaluated. Avascular areas correlated significantly with severe RP (P < 0·002), bone resorption (P < 0·007) and diffuse SS (P < 0·008). Conclusions Digital epiluminescence seems to be a useful and reliable technique in the evaluation of capillary nailfold morphological changes. This technical variation allows the identification of specific capillaroscopic patterns associated with connective tissue diseases. It also permits us to differentiate PRP from SRP. The results obtained with this technique are similar to those previously reported using standard capillaroscopy devices.     

Impact of systemic to topical steroids switch on the outcome of drug reaction with eosinophilia and systemic symptoms (DRESS): A monocenter retrospective study of 20 cases

BackgroundThere is no consensus on the treatment of drug reaction with eosinophilia and systemic symptoms (DRESS). At our center, systemic steroids (SS) are used for severe cases while topical steroids (TS) are used for mild and moderate forms.ObjectivesTo investigate the short-term outcome for patients with DRESS receiving SS as first-line therapy before being transferred to our department and then switched to TS after admission.MethodsA retrospective monocenter study in DRESS patients (RegiSCAR score ≥ 4) transferred to our dermatology department from a different setting between 07/2012 and 06/2018 and who had received SS before being transferred. Epidemiological, clinical and laboratory data were collected, as well as details of treatment modalities and outcome.ResultsTwenty patients were included. On admission to our department, 4 were assessed as having severe DRESS and continued on SS, while 16 were assessed as mild/moderate DRESS and were switched to TS. Among these 16 patients, the outcome on TS was favorable for 12 and quickly unfavorable for 4, who had to be switched back to SS. Retrospective analysis of the initial data (before transfer) showed that these 4 patients had previously had a greater number of severity criteria than the other 12.ConclusionCaution is needed not only when deciding to initiate SS in DRESS but also on withdrawal of these drugs. Our series suggests that when SS are used as first-line therapy in DRESS patients with initial severity criteria, they should not be withdrawn quickly for a switch to TS, even where progression appears favorable, due to the risk of relapse.     

Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity

Background Hidradenitis suppurativa (HS) is a long‐standing disease with abscess and often fistula formation, predominantly in the axillae and groins. The disease is difficult to treat and has a severe impact on quality of life. A clinically relevant system for scoring disease severity is lacking in HS. Objectives To evaluate the modified Hidradenitis Suppurativa Score (HSS) and to study the impact of body mass index (BMI) and smoking habits on disease severity. Methods Two hundred and fifty‐one consecutive patients with HS referred to a clinic with special interest in the disease were included, of whom 115 were scored. Points were given for regions involved, types of lesion (nodules, fistulas), total area involved and whether lesions were separated by normal skin. Background characteristics included BMI and smoking habits. Two hundred and forty‐six patients completed the Dermatology Life Quality Index (DLQI). Results The median (interquartile range, IQR) HSS for all patients was 38 (18–66): women 38 (18–71) and men 37 (19–51). Median (IQR) HSS for smokers was 41 (22–75·5), former smokers 27 (16–53) and nonsmokers 22 (10–57). Median (IQR) HSS for patients with BMI < 25 kg m^?2 was 32 (12–54), BMI 25–30 kg m^?2 44 (22–56) and BMI ≥ 30 kg m^?2 50 (18–86). Mean ± SD DLQI for the whole group of patients was 10·3 ± 7·5, median 9, and showed no significant differences between the groups studied. There was a significant positive correlation of fair degree between HSS and DLQI. There were significant differences in HSS between nonsmokers and smokers as well as between women of normal weight compared with obese women. Conclusions The modified HSS is simple and practical and it extracts important clinical information. A connection between disease severity and BMI as well as smoking habits in patients with HS is presented. The results suggest that the HSS may be a relevant outcome measure in future therapeutic trials in HS.     

Interobserver variability of clinical scores in hidradenitis suppurativa is low

Background Hidradenitis suppurativa (HS) is a chronic recurrent disease with scars and sinus tract formation that causes substantial impact on quality of life. For evaluation of HS and treatment results, a scoring system for disease severity (Hidradenitis Suppurativa Score, HSS) has been proposed. Objectives To describe the interobserver reliability of the HSS and further to document its correlation with risk factors and other measures of disease severity. Methods Sixty‐one consecutive patients with HS, referred to a clinical centre with special interest in the disease, were scored according to the HSS protocol: eight patients by four dermatologists together, 23 patients by all four observers independently and 30 patients by a single observer. Interobserver variability in HSS between the four observers was investigated in the group of 23 patients. Patients’ reports of weight and height, smoking habits etc., were collected, as well as Dermatology Life Quality Index (DLQI) questionnaires. Results The interobserver concordance of HSS was 0·95. Median (interquartile range, IQR) HSS for all patients was 40 (18–73); women 39 (16–68); men 60·5 (30–95). Median (IQR) HSS for nonsmokers was 26 (12–65); former smokers 30 (10–56); smokers 44 (26–108). Median (IQR) HSS for normal weight patients was 12 (10–30); overweight 43 (25–58); obese 51 (24–95). Mean ± SD DLQI for all patients was 11·3 ± 8·6. Conclusions HSS is simple to use and shows low interobserver variability. The score correlates with suggested risk factors, indicating that it reflects a valid estimation of disease severity.     

Lymphomatoid papulosis in association with mycosis fungoides: A clinical and histopathologic review of five Taiwanese cases

Background/ObjectivesLymphomatoid papulosis (LyP) is a cutaneous CD30+ lymphoproliferative disorder characterized by recurrent, self-healing lesions with a chronic clinical course. Approximately 10–20% of the patients have lymphomas, including mycosis fungoides (MF). LyP in association with MF is not well documented in Taiwan. We aimed to describe the clinicopathologic characteristics of LyP with MF in a Taiwanese case series of LyP.MethodsA retrospective clinicopathologic study was performed on cases of LyP with MF diagnosed in our Department during the period 1990–2012. The diagnosis of LyP and MF were based on their characteristic clinical and pathologic features as well as correlation with the clinical course of the specific skin lesions.ResultsA total of 24 cases of LyP (10 males and 14 females, age 18–63 years, mean 40.4 years) were included. Multiple biopsies were often done in individual patients during the clinical course to establish the diagnosis of LyP and MF. LyP was further classified pathologically as type A (n = 16), B (n = 3), C (n = 3), and mixed type with A&B (n = 1) and A&C (n = 1). Five cases (21%) also had MF; two had juvenile-onset LyP and three had juvenile-onset MF (one with hypopigmented MF, one with hyperpigmented MF, two with CD8+ LyP, and two with CD8+ MF). In the case of juvenile-onset hypopigmented CD8+ MF, the patient developed CD8+ LyP 25 years after the onset of MF and died of aggressive epidermotropic CD8+ lymphoma involving the skin and lung.ConclusionMF occurred in five of the 24 cases (21%) in the present series of LyP. These five cases had several unusual clinical and pathologic features, including subtle or uncommon skin manifestation of MF and more frequent juvenile-onset and CD8 phenotype of LyP and/or MF lesions. Long-term follow-up and repeated biopsy of selected skin lesions are necessary for correct diagnosis and proper treatment of both diseases.     

Assessment of thyroid disorders in patients with rosacea: a large case-control study

BackgroundThe frequency of autoimmune diseases and thyroid cancer has been increasingly reported in association with rosacea. However, studies investigating thyroid diseases in rosacea are scarce with conflicting results.ObjectiveTo investigate the relationship between thyroid disorders and rosacea.MethodsA large case-control study on age- and gender-matched 2091 rosacea patients and 9572 controls was conducted. Rosacea patients using the rosacea-specific ICD codes were compiled from the hospital records. Additionally, all participants were evaluated in terms of the presence of hypothyroidism and hyperthyroidism. Conditional logistic regression analysis was used to compute case-control odds ratios (OR) with 95% confidence intervals.ResultsThe analysis comprehended 2091 rosacea patients (1546 female, 545 male; mean 48.73 ± 14.53 years) and 9572 controls (7009 female, 2563 male; mean 48.73 ± 15.1 years). Whereas the rate of hypothyroidism was significantly higher in rosacea patients (OR = 1.3, 95% CI 1.13–1.49, p < 0.001), there was no significant difference in the rate of hyperthyroidism between the groups (OR = 1.12, 95% CI 0.81–1.53, p = 0.497). Stratification for gender revealed a significant association between hypothyroidism and rosacea in females (OR = 1.27, 95% CI 1.1–1.47, p = 0.002) and males (OR = 1.58, 95% CI 1.04–2.4, p = 0.032). The frequency of hypothyroidism in rosacea patients increased towards the age range of 40–49 and then decreased, parallel with the hypothyroidism frequency of the study population.Study limitationsDifferent subtypes and severities of rosacea were not distinguished.ConclusionsHypothyroidism may be a comorbidity of rosacea and investigation for hypothyroidism may be appropriate when evaluating rosacea patients.     

Subcutaneous phaeohyphomycosis due to Exophiala jeanselmei following renal transplantation: A case report with a published work review of phaeohyphomycosis in Japan

We describe a case of cutaneous phaeohyphomycosis following renal transplantation and include a review of the previously published Japanese cases. A 40-year-old Japanese woman taking immunosuppressants following renal transplantation 6 years prior presented to our hospital with a subcutaneous lesion on her right leg. Skin biopsy revealed an abscess, and culture confirmed Exophiala jeanselmei to be the causative agent. Treatment with itraconazole combined with surgical drainage was effective, and the lesion disappeared after 15 months. Upon review of 128 Japanese phaeohyphomycosis cases, it was found that more than 80% of the cases occurred in patients aged more than 60 years, and most cases involved underlying diseases associated with immunodeficiency. E. jeanselmei was the most common etiologic fungus. Recently, however, the Exophiala species has been reclassified based on molecular identification, and cases due to E. jeanselmei decreased with the concomitant increase of cases due to Exophiala oligosperma and Exophiala xenobiotica. In approximately half of the cases, lesions were treated by surgical removal, with or without concomitant antifungal drugs. Itraconazole was the antifungal agent most frequently used. In many cases, the disease course was reported as either healing or improving. There was no difference in either treatment or prognosis based on the etiologic species of fungus.     

A prospective randomized controlled trial assessing the efficacy of adjunctive hyperbaric oxygen therapy in the treatment of hidradenitis suppurativa

Hyperbaric oxygen therapy (HBOT) appears to enhance wound healing, increase bactericidal activity, and act synergistically with a number of antibiotics. The aim of this study was to evaluate the efficacy of HBOT as an adjunctive therapy in patients with hidradenitis suppurativa (HS) treated with a combination of systemic rifampicin and clindamycin. The study was a prospective, single‐center, single‐dose, open‐label, randomized controlled clinical study of HBOT in patients with moderate to severe HS. Efficacy was measured by modified Sartorius score (SS), HS Severity Index (HSSI), Dermatology Life Quality Index (DLQI), and a visual analog scale (VAS) before treatment and after the completion of 4 and 10 weeks of treatment. Erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) levels were also measured. Forty‐three patients were enrolled in the study. More patients in the HBOT than in the control group showed a decrease of ≥50% from baseline parameters at week 10 for SS (100%), HSSI (100%), DLQI (95.5%), VAS (100%), ESR (100%), and CRP (72.7%). Clinically and statistically significant improvements from baseline were observed at 4 and 10 weeks in HSSI (P = 0.009 at both), SS (P = 0.021 at both), and DLQI (P = 0.044 at week 4, P = 0.009 at week 10). Adjunctive HBOT was considered to be effective in significantly improving antibiotic treatment of HS. The treatment was well tolerated, and no unexpected safety issues were identified.     

Modulation of TRPV1 function by Citrus reticulata (tangerine) fruit extract for the treatment of sensitive skin

Background

Sensitive skin (SS) is a clinical syndrome defined by the occurrence of unpleasant sensations (such as stinging, burning, pain, pruritus, and tingling) in response to stimuli that normally should not provoke them. According to growing evidence, transient receptor potential vanilloid subtype 1 (TRPV1) has elevated expression in individuals with SS and is linked with the severity of SS symptoms. However, its pathogenesis is still unknown.

Objective

Herein, Citrus reticulata (Tangerine) fruit extract (CR) was obtained and examined for its effect on SS with a focus on TRPV1 stimulation and expression.

Methods

A recombinant hTRPV1 over-expression cell line (HaCaT-TRPV1-OE cell) was constructed to screen substances and extracts from several plants. Intracellular calcium mobilization was monitored by Flexstation 3 and a fluorescence microscope using Fluo 8 AM fluorophore. Next, immunofluorescence was used to detect the TRPV1 expression under different stimulants treated for 24 h. To investigate the relief and increased tolerance of CR to lactic acid-induced skin discomfort, clinical tests were carried out on the nasolabial folds or cheek areas.

Results

According to the obtained results, compared to HaCaT cells, HaCaT-TRPV1-OE cells showed a higher expression of TRPV1. Neuronal hyperresponsiveness in SS triggered by capsaicin (CAP), lactic acid, phenoxyethanol or nicotinamide may be through activation of TRPV1 and increased TRPV1 expression. CAP activates TRPV1 in HaCaT-TRPV1-OE cells, and more than 100 plants or chemicals were tested for their inhibitory effects before being screened for CR. CR (1%–4%) inhibited TRPV1 activation induced by CAP or phenoxyethanol or nicotinamide. Meanwhile, CR (0.25%) suppressed TRPV1 protein expression induced by phenoxyethanol or lactic acid. In vivo results showed that CR not only instantly relieved lactic acid-induced skin discomfort under 5 min but also enhanced skin tolerance to lactic acid after 7 days of continuous use.

Conclusions

Topical application of CR showed an instant and long-lasting improvement in SS by modulating the activation and expression of TRPV1. Moreover, it has been suggested that CR might act as a TRPV1 inhibitor to reduce skin irritation or sensitivity.     

Effect of monochromatic excimer light on palmoplantar pustulosis: A clinical study performed in a private clinic by a dermatological specialist

Palmoplantar pustulosis (PPP) is currently treated with various modalities, including excimer light, a form of ultraviolet lamp. This study reports effect of excimer light treatment in 34 Japanese PPP patients treated at a private clinic by one doctor, who was certified as a dermatological specialist by the Japanese Dermatological Association. The statistical analyses were performed upon a collaborative basis with faculties in universities. Disease response scores were determined by response to excimer light treatment. Scores of 1, 2, 3 or 4 were assigned to patients whose palmoplantar pustular psoriasis area and severity index (PPPASI) decreased to 25% or less, 25.1–50%, 50.1–75% or more than 75.1% of pretreatment PPPASI, respectively. In this study, 44.1% PPP cases had scores of 1 or 2, and considered good responders to excimer light treatment. There were no statistical differences between males and females, and between older (≥40 years) and younger groups (≤39 years) in terms of disease response score. Disease duration did not show any significant difference among these scores. Treatment times, total amount of ultraviolet and total treatment duration showed significant differences between score 1 and score 4 groups (P = 0.0164, =0.0137 and =0.0267, respectively). Particular interest was paid to smoking habits. Smoking in male patients was significantly higher than that in female patients (P = 0.0169). There was no statistical difference between smokers and non‐smokers in terms of response to excimer light. In conclusion, this study suggested that excimer light is useful for both initial regimen and suppression of exacerbation in treatments of PPP.     

Loricrin downregulation and epithelial‐related disorders: a systematic review

Loricrin downregulation has been associated with age‐related changes as well as inherited and inflammatory skin diseases. We hypothesize that changes in loricrin could be more related to altered barrier function and consequently disorders that affect epithelial cells, such as psoriasis, atopic dermatitis (AD), erythrokeratoderma, loricrin keratoderma (LK) and periodontitis. The aim of this review is to summarize what is known about the association between loricrin downregulation and epithelial‐related disorders (ERDs). A search was performed on the following databases: Medline, Cochrane Library, PubMed, EMBASE, Lilacs, Scopus and Google Scholar, resulting in 16 included articles. Loricrin keratoderma was the ERD most frequently associated with loricrin mutations (730insG, 709insC and 578insG; 5/7 cases – 71.44 %). Atopic dermatitis was the ERD most frequently associated with loricrin downregulation (2/7 cases – 28.6 %). Mutilating palmoplantar keratoderma, progressive symmetrical erythrokeratoderma and a new type of erythrokeratoderma were not associated with any mutations. At the gene level, periodontitis patients showed the highest decrease (–6.89x), followed by AD (–6.5x) and psoriasis patients (–0.5x). In summary, loricrin mutation and downregulation were associated with several ERDs. The diversity in disease presentation is likely related to whether there is a total loss of loricrin, mislocalization and/or if the mutant form of loricrin causes dysfunction of other proteins and/or changes in cornification.     

Four mild but refractory cases of pemphigus foliaceus successfully treated with intravenous immunoglobulin

Intravenous immunoglobulin (IVIG) is a potential second line of therapy for pemphigus, with increasing evidence of its effectiveness and safety, although oral corticosteroids remain the first treatment for pemphigus. IVIG is usually applied in severe cases of pemphigus, particularly pemphigus vulgaris (PV). Pemphigus foliaceus (PF) caused by immunoglobulin PF autoantibodies to desmoglein 1 (Dsg1) is usually milder than PV. However, PF cases are occasionally resistant to corticosteroids and require long‐term treatment to control the disease, leading to various adverse effects. IVIG was used in patients with relatively mild PF, who were resistant to therapies with corticosteroids and dapsone. We assessed the disease severity by Pemphigus Disease Area Index (PDAI) and measured anti‐Dsg1 antibody indices by enzyme‐linked immunosorbent assay, before and 4 months after IVIG. Four Japanese female PF patients (57.3 ± 8.6 years) were treated with a single cycle of IVIG (400 mg/kg per day for five consecutive days) in combination with the previous therapies. Within 1–2 months of addition of IVIG, all PF cases showed remarkable improvement of skin lesions, and PDAI also markedly decreased. For 2 years after IVIG, no apparent exacerbation was observed. Anti‐Dsg1 antibody indices decreased in all cases during the 2 years. IVIG could be a potential treatment for not only severe cases of PV but also mild and refractory cases of PF. IVIG may trigger the shift from intractable condition to remission via non‐pathogenic anti‐Dsg1 antibodies or some mechanisms excluding anti‐Dsg1 antibody.     

Dermatoses in international travellers seen at Bordeaux teaching hospital travel clinic, 2015–2018: a GeoSentinel-based study

Skin disorders are frequent in travellers, but data vary between different studies. The objectives of the current study were to describe imported dermatoses in the Bordeaux GeoSentinel prospective database between August 2015 and March 2018. During the study period, 1025 travellers were seen in the clinic, 201 of them with dermatoses. Patients with skin disorders were more likely to be aged > 60 years (OR = 1.88, 95% CI 1.22–2.89), to be tourists (OR 3.04, 95% CI 2.03–4.55) and to have travelled to South America (OR = 2.18, 95% CI 1.29–3.67), and less likely to have sought pretravel advice (OR = 0.53, 95% CI 0.31–0.91). Skin bacterial infections (19.4%) and Zika virus infections (18.4%) were the most common dermatoses. Dengue fever and bacterial skin infections were the leading causes of hospitalization. The contribution of tropical diseases to imported dermatoses remains important. Lack of pretravel advice puts tourists at risk of significant diseases such as dengue fever, Zika virus and bacterial infections.     

Chronological association between alopecia areata and autoimmune thyroid diseases: A systematic review and meta‐analysis

The association between alopecia areata (AA) and autoimmune thyroid diseases (AITD) has been suggested; however, the chronological relationship between AA and AITD remains elusive. A systematic review and meta‐analysis were conducted to assess the association between AA and AITD focusing on the prevalence of thyroid antibodies, thyroid diseases and serological thyroid dysfunctions, respectively. Data collection was performed in October 2018 by searching for articles in two electronic databases: Medline and Embase. Case–control, cohort and cross‐sectional studies were included. Meta‐analysis of studies eligible for quantitative synthesis was performed to estimate pooled odds ratios of thyroid antibodies; thyroid peroxidase antibody (TPO‐Ab) and thyroglobulin antibody (TG‐Ab), diagnosed thyroid diseases and serological thyroid dysfunctions. Four hundred and eighty nine research papers were identified and 17 studies with 262 581 patients and 1 302 655 control subjects were included for quantitative synthesis. AA was significantly associated with both TPO‐Ab and TG‐Ab. In comparison, there was no significant association between AA and diagnosed hypothyroidism or hyperthyroidism and serological hypothyroidism or hyperthyroidism. In conclusion, AA is significantly associated with the existence of thyroid antibodies rather than with clinical or laboratory thyroid abnormality. Lack of long‐term follow‐up data is a limitation of the existing published work. Our findings do not support routine screening of thyroid diseases for asymptomatic AA patients but highlight the potential future risk of AITD particularly in severe and refractory AA.