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1.
Br J Dermatol ; 190(6): 904-914, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38169316

ABSTRACT

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory and scarring disease with a wide spectrum of disease severity. The amount of scarring is proportional to the preceding tissue damage and poses a challenge to patients. Severe HS is most often treatment recalcitrant, but hypothetically avoidable through early biologic treatment. Early prediction of individual risk of disease progression is therefore essential for patient management. OBJECTIVES: To investigate risk factors associated with disease progression and to design an algorithm capable of predicting disease -progression. METHODS: A prospective cohort study of 335 Hurley III-naïve patients with HS, not treated with biologics, was followed for a median of 2 years. Potential risk factors covered basic demographics, HS anamnestic factors and clinical HS factors collected during physical examination. Two separate Cox proportional hazard regression (CPHR) analyses were conducted. A summated 'progression score' was calculated and used in the predictive algorithm of severe disease. Subsequent bootstrap sampling was used to validate the predictability of the predictive algorithm. RESULTS: The CPHR analysis of Transition to severe disease found that active smoking [hazard ratio (HR) 4.01, 95% confidence interval (CI) 1.71-9.40, P = 0.001]; body mass index (BMI) points > 25 at baseline (each point: HR 1.06, 95% CI 1.02-1.09, P < 0.001); active disease in 2 (HR 4.26, 95% CI 1.23-14.84, P = 0.02) and ≥ 3 areas (HR 6.54, 95% CI 1.89-22.72, P = 0.003) all constituted substantial risk factors. Conversely, the CPHR analysis of Disease progression did not yield results of clinical relevance. A 'progression score' of 3.04 was used as a threshold in the predictive algorithm of Transition to severe disease and achieved the following test specifics: sensitivity = 0.51, specificity = 0.86, positive predictive value = 0.50, negative predictive value = 0.86. CONCLUSIONS: We found a disparity between factors increasing the risk of simple Disease progression and those increasing the risk of Transition to severe disease. For the latter, active smoking, BMI points > 25, active disease in 2 or ≥ 3 areas were all shown to be the clinically relevant factors that could be used to construct an algorithm that correctly predicted progression to severe HS in more than half of all instances.


Subject(s)
Algorithms , Disease Progression , Hidradenitis Suppurativa , Humans , Hidradenitis Suppurativa/diagnosis , Hidradenitis Suppurativa/pathology , Male , Female , Adult , Prospective Studies , Middle Aged , Risk Factors , Proportional Hazards Models , Denmark/epidemiology , Smoking/adverse effects , Smoking/epidemiology , Young Adult
2.
Dermatology ; 240(3): 369-375, 2024.
Article in English | MEDLINE | ID: mdl-38354718

ABSTRACT

INTRODUCTION: Data concerning the global burden of hidradenitis suppurativa (HS) are limited. Reported prevalence estimates vary between 0.0003% and 4.1%, and data from various geographical regions are still to be collected. Previously reported prevalences have been limited by the methodological approach and source of data. This has resulted in great heterogeneity as prevalence data from physician-diagnosed cases poorly match those of self-reported apparent HS disease. METHODS: The Global Hidradenitis Suppurativa Atlas (GHiSA) introduces an innovative approach to determine the global prevalence of HS. This approach involves using a previously validated questionnaire to screen apparently healthy adults accompanying a patient to a non-dermatological outpatient clinic visit in a hospital or a private/family medicine clinic. The screening questionnaire (i.e., the index test) is combined with a subsequent physician-based in-person validation (i.e., the reference standard) of the participants who screen positive. Approximately ten percent of the screen-negative participants are also clinically assessed to verify the diagnostic precision of the test. The local prevalence (pi) will be estimated from each country that submits the number of patients who are HS positive according to the index test and clinical examination (n), and the corresponding total number of observations (N). CONCLUSION: The GHiSA Global Prevalence studies are currently running simultaneously in 58 countries across six continents (Africa, Europe, Australia, North America, South America, and Asia). The goal of the combined global proportion is the generation of a single summary (i.e., proportional meta-analysis), which will be done after a logit transformation and synthesized using a random-effects model. The novel standardization of the Global Prevalence Studies conducted through GHiSA enables direct international comparisons, which were previously not possible due to substantial heterogeneity in past HS prevalence studies.


Subject(s)
Global Health , Hidradenitis Suppurativa , Humans , Hidradenitis Suppurativa/epidemiology , Hidradenitis Suppurativa/diagnosis , Prevalence , Surveys and Questionnaires , Adult
3.
Mycoses ; 67(7): e13760, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38943042

ABSTRACT

BACKGROUND: Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent. OBJECTIVES: The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC). METHODS: We used Wood's light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method. RESULTS: Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard-to-treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood's light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L. CONCLUSION: Use of Wood's light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness.


Subject(s)
Antifungal Agents , Disease Outbreaks , Drug Resistance, Fungal , Microbial Sensitivity Tests , Microsporum , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Humans , Microsporum/drug effects , Male , Female , Denmark/epidemiology , Adult , Child , Terbinafine/pharmacology , Terbinafine/therapeutic use , Middle Aged , Tinea Capitis/drug therapy , Tinea Capitis/microbiology , Tinea Capitis/epidemiology , Griseofulvin/pharmacology , Griseofulvin/therapeutic use , Child, Preschool , Adolescent , Young Adult , Tinea/drug therapy , Tinea/microbiology , Tinea/epidemiology , Itraconazole/pharmacology , Itraconazole/therapeutic use , Aged , Fluconazole/pharmacology , Fluconazole/therapeutic use
4.
Article in English | MEDLINE | ID: mdl-39001674

ABSTRACT

BACKGROUND: There has been a global rise in cases of dermatophytosis and, in particular, recalcitrant and recurrent cases on tinea of the glabrous skin. This phenomenon, particularly prevalent in India, has been linked to the concerning rise of antifungal resistance. The challenge is amplified by a dearth of comprehensive, international data to understand the global scope and characteristics of such cases. OBJECTIVES: This study aims to collate international insights, focusing on areas outside Europe (as this was previously published), to map the extent and characteristics of clinical and, where possible, laboratory confirmed tinea of the glabrous skin through an online survey administered to dermatologists globally. METHODS: An online survey was distributed from February 2022 to July 2023 and captured data on respondents' experience of recalcitrant and recurrent tinea of the glabrous skin over the preceding 3 years. RESULTS: A total of 260 responses were received spreads across 36 countries, excluding Europe. In total, 91.7% reported seeing cases of recalcitrant or recurrent tinea of the glabrous skin over the preceding 3 years. Common anatomical sites affected were the trunk and groin. T. mentagrophytes and T. rubrum were the predominant species implicated, and there were low rates of laboratory confirmed dermatophyte resistance. CONCLUSIONS: The high rates of reported recalcitrant and recurrent tinea of the glabrous skin underscore an urgent need for global collaborative efforts and enhanced diagnostic measures. The findings advocate for the establishment of a standardized global disease registry, regulation of over-the-counter antifungal and steroid combinations, correlation of clinical suspicion with laboratory confirmed drug resistance and exploration of alternative therapeutic strategies to mitigate the burgeoning challenge of dermatophyte resistance.

5.
J Dtsch Dermatol Ges ; 22(1): 23-27, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38128111

ABSTRACT

Acne fulminans (AF) is a rare, serious, sudden-onset and long-lasting skin disease that causes scarring of face and body. Standard treatment with combined long-term isotretinoin and prednisolone is not always sufficient and has a well-known propensity for adverse effects leaving an unmet need for improved therapy. Case reports suggest that tumor necrosis factor (TNF)-α inhibitors may play a role in the management of AF. In a 3-year retrospective data collection from two dermatology centers and literature review of clinical cases of acne fulminans treated with anti-TNF-α therapy, three clinical cases and twelve literature cases were identified. A total of five different TNF-α inhibitors have been tested, with adalimumab being the most commonly used. Clinical response was seen after 1 month in 2/3 (67%) clinical cases and 5/12 (42%) literature cases, respectively, and treatment was successful in 2/3 (67%) and 11/12 (92%) after a median 3-7 months. All reported adverse effects were mild and reversible. Anti-TNF-α treatment may provide rapid improvement in patients with AF when initial treatment with isotretinoin and prednisolone fails. However, randomized controlled trials are lacking, and exact dosage and timing need to be explored before clinical implementation.


Subject(s)
Acne Vulgaris , Dermatologic Agents , Humans , Isotretinoin/therapeutic use , Isotretinoin/adverse effects , Tumor Necrosis Factor-alpha , Retrospective Studies , Tumor Necrosis Factor Inhibitors , Acne Vulgaris/pathology , Prednisolone/therapeutic use
6.
Dermatology ; 239(3): 362-367, 2023.
Article in English | MEDLINE | ID: mdl-36630943

ABSTRACT

BACKGROUND: Previously, a new dichotomous outcome was developed, calculated as 55% reduction in the International Hidradenitis Suppurativa 4 (IHS4-55) score. It was validated in datasets of adalimumab and placebo-treated HS patients. External validation is an important aspect of clinical outcomes. OBJECTIVES: We aimed to externally validate the novel dichotomous IHS4-55 in a non-biologic treated dataset of HS patients. METHODS: Data from a previously published European-wide prospective clinical study of antibiotic treatment of HS patients were used to assess the association of IHS4-55 achievement with individual reduction in inflammatory nodules, abscesses, and draining tunnels. Moreover, the associations between IHS4-55 positivity and achievement of the minimal clinically important differences (MCIDs) for Dermatology Life Quality Index (DLQI), Numerical Rating Scale (NRS) Pain, and NRS Pruritus were analyzed. RESULTS: Data were obtained from 283 individual patients, of which 36.4% (103/283) were treated with clindamycin and rifampicin and 63.6% (180/283) with tetracyclines for 12 weeks. Achievers of the IHS4-55 demonstrated a significant reduction the counts of inflammatory nodules, abscesses, and draining tunnels (all p < 0.001). Additionally, IHS4-55 achievers had an odds ratio for achieving the MCID of DLQI, NRS Pain, and NRS Pruritus of 2.16 (95% CI 1.28-3.65, p < 0.01), 1.79 (95% CI 1.10-2.91, p < 0.05), and 1.95 (95% CI 1.18-3.22, p < 0.01), respectively. CONCLUSIONS: This study shows the external validity of the novel IHS4-55 by demonstrating a significant association between IHS4-55 achievement and a reduction in inflammatory lesion counts as well as achievement of MCIDs for DLQI, NRS Pain, and NRS Pruritus in an antibiotic-treated cohort. These findings support the use of the IHS4-55 as a novel primary outcome measure in clinical trials.


Subject(s)
Hidradenitis Suppurativa , Humans , Hidradenitis Suppurativa/complications , Hidradenitis Suppurativa/drug therapy , Anti-Bacterial Agents/therapeutic use , Prospective Studies , Abscess , Severity of Illness Index , Pruritus/drug therapy , Pain/drug therapy , Pain/etiology , Treatment Outcome
7.
Dermatology ; 238(1): 60-79, 2022.
Article in English | MEDLINE | ID: mdl-34058736

ABSTRACT

BACKGROUND: Dermatophytosis is commonly encountered in the dermatological clinics. The main aetiological agents in dermatophytosis of skin and nails in humans are Trichophyton (T.) rubrum, T. mentagrophytes and T. interdigitale (former T. mentagrophytes-complex). Terbinafine therapy is usually effective in eradicating infections due to these species by inhibiting their squalene epoxidase (SQLE) enzyme, but increasing numbers of clinically resistant cases and mutations in the SQLE gene have been documented recently. Resistance to antimycotics is phenotypically determined by antifungal susceptibility testing (AFST). However, AFST is not routinely performed for dermatophytes and no breakpoints classifying isolates as susceptible or resistant are available, making it difficult to interpret the clinical impact of a minimal inhibitory concentration (MIC). SUMMARY: PubMed was systematically searched for terbinafine susceptibility testing of dermatophytes on October 20, 2020, by two individual researchers. The inclusion criteria were in vitro terbinafine susceptibility testing of Trichophyton (T.) rubrum, T. mentagrophytes and T. interdigitale with the broth microdilution technique. The exclusion criteria were non-English written papers. Outcomes were reported as MIC range, geometric mean, modal MIC and MIC50 and MIC90 in which 50 or 90% of isolates were inhibited, respectively. The reported MICs ranged from <0.001 to >64 mg/L. The huge variation in MIC is partly explained by the heterogeneity of the Trichophyton isolates, where some originated from routine specimens (wild types) whereas others came from non-responding patients with a known SQLE gene mutation. Another reason for the great variation in MIC is the use of different AFST methods where MIC values are not directly comparable. High MICs were reported particularly in isolates with SQLE gene mutation. The following SQLE alterations were reported: F397L, L393F, L393S, H440Y, F393I, F393V, F415I, F415S, F415V, S443P, A448T, L335F/A448T, S395P/A448T, L393S/A448T, Q408L/A448T, F397L/A448T, I121M/V237I and H440Y/F484Y in terbinafine-resistant isolates.


Subject(s)
Antifungal Agents/pharmacology , Drug Resistance, Fungal/genetics , Microbial Sensitivity Tests , Tinea/drug therapy , Trichophyton/drug effects , Humans , Mutation , Squalene Monooxygenase/genetics , Terbinafine/pharmacology , Tinea/microbiology , Trichophyton/genetics
8.
Mycoses ; 65(7): 741-746, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35535729

ABSTRACT

BACKGROUND: Treatment of tinea pedis and onychomycosis is complicated by high rates of reinfection and the emergence of terbinafine-resistant strains of Trichophyton spp. Effective disinfection of contaminated socks is an important measure. Appropriate washing reduces the risk of reinfection and is paramount in treating tinea pedis and onychomycosis. OBJECTIVES: The aim of this study was to describe the effect of commonplace disinfection methods using socks pieces inoculated with terbinafine-resistant or terbinafine-susceptible isolates of Trichophyton spp. METHODS: Sock pieces were inoculated with seven terbinafine-resistant isolates of Trichophyton spp. with known mutations in the SQLE-gene (T. rubrum (n = 3), T. interdigitale (n = 1) and T. indotineae (n = 3)) and six terbinafine-susceptible isolates of Trichophyton spp. (T. rubrum (n = 3) and T. interdigitale (n = 3)). Methods of disinfection included soaking in a quaternary ammonium (QAC) detergent (0.5, 2 and 24 h), freezing at -20°C (0.5, 12 and 24 h), domestic and steam washing (both at 40°C with detergent). Sock pieces were cultured for 4 weeks following disinfection. The primary end point was no growth at the end of week 4. RESULTS: Soaking in a QAC-detergent for 24 h procured at disinfectant rate of 100% (13/13), whilst soaking in 0.5 and 2 h had a disinfectant rate of 46.2% (6/13) and 84.6% (11/13), respectively. Domestic washing (40°C with detergent) produced a disinfectant rate of 7.7% (1/13). Freezing at -20°C (0.5, 12 and 24 h) and steam washing (40°C with detergent) had no disinfectant properties. CONCLUSIONS: Soaking in a QAC-detergent for 24 h effectively disinfected sock pieces contaminated with dermatophytes.


Subject(s)
Arthrodermataceae , Disinfectants , Onychomycosis , Antifungal Agents/pharmacology , Arthrodermataceae/genetics , Detergents , Disinfectants/pharmacology , Disinfection , Drug Resistance, Fungal/genetics , Humans , Microbial Sensitivity Tests , Onychomycosis/drug therapy , Onychomycosis/prevention & control , Reinfection , Steam , Terbinafine/pharmacology , Tinea Pedis/prevention & control , Trichophyton
9.
Pediatr Dermatol ; 39(6): 855-865, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36130720

ABSTRACT

Onychomycosis is one of the most common nail diseases in adults but is described as infrequent in children. Data are, however, scattered and diverse. Studies have nevertheless suggested that the prevalence of onychomycosis is increasing in children lately and the aim of this review was therefore to examine this problem. Two authors individually searched PubMed, Embase, and Cochrane Library for articles on epidemiology and prevalence of onychomycosis in children. The literature search was conducted in accordance per PRISMA guidelines. In total 1042 articles were identified of which 23 were eligible for inclusion. One of the articles presented two studies and a total of 24 studies were therefore included. Seventeen studies presented data of the prevalence of onychomycosis in children in the general population and seven studies among children visiting a dermatological and pediatric department or clinic. The prevalence ranged from 0% to 7.66% with an overall discrete increase of 0.66% during the period 1972 to 2014 in population studies (not statistically significant). This review supports a trend towards an increased prevalence of onychomycosis in children, albeit based on a paucity of studies. The data suggests an increasing prevalence of onychomycosis with age, and co-infection with tinea pedis (reported in 25% of the studies). The most common pathogen reported was Trichophyton rubrum and onychomycosis was more prevalent in toenails compared to fingernails. The general characteristics of onychomycosis in children are thus similar to those described in adults.


Subject(s)
Onychomycosis , Adult , Child , Humans , Nails , Onychomycosis/epidemiology , Prevalence , Tinea Pedis/epidemiology , Trichophyton
10.
BMC Microbiol ; 21(1): 72, 2021 03 04.
Article in English | MEDLINE | ID: mdl-33663381

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) patients have an altered skin bacterial community, with an abundance of Staphylococcus aureus associated with flares, highlighting that microbial organisms may be important for disease exacerbation. Despite strong evidence of association between bacterial skin colonisation and AD, very limited knowledge regarding the eukaryotic microbial community, including fungi and ectoparasites, in AD exists. In this study, we compared the skin and nasal eukaryotic microbial community between adult AD patients (n = 55) and non-AD healthy controls (n = 45) using targeted 18S rRNA amplicon sequencing. Analysis was based on the presence or absence of eukaryotic microorganisms. RESULTS: The cutaneous composition of the eukaryotic microbial community and the alpha-diversity differed significantly between AD patients and non-AD individuals, with increased species richness on AD skin. Alpha-diversity and beta-diversity were similar on lesional and non-lesional skin of patients. The ectoparasite Demodex folliculorum and the yeast Geotrichum candidum were significantly more prevalent on the skin of AD patients. The prevalence of D. folliculorum on lesional skin was greater among patients recently treated with topical corticosteroid. Malassezia was one of the most frequently detected genera at all sites, with M. globosa and M. restricta being the most prevalent. M. restricta was under represented in the anterior nares of AD patients as compared to the non-AD control population. CONCLUSION: Significant differences in the eukaryotic microbial communities were found between AD patients and non-AD individuals, with the most striking finding being the significantly overrepresentation of D. folliculorum on AD skin. Whether D. folliculorum can contribute to skin inflammation in AD needs further investigation.


Subject(s)
Dermatitis, Atopic/microbiology , Dermatitis, Atopic/parasitology , Fungi/genetics , Mites/genetics , RNA, Ribosomal, 18S/genetics , Skin/microbiology , Animals , Biodiversity , Fungi/classification , Fungi/isolation & purification , Humans , Mites/classification
11.
J Am Acad Dermatol ; 85(2): 369-378, 2021 08.
Article in English | MEDLINE | ID: mdl-33484766

ABSTRACT

BACKGROUND: Tetracyclines and clindamycin plus rifampicin combination therapy are both considered first-line therapy in current hidradenitis suppurativa guidelines. However, evidence for their efficacy is drawn from small studies, often without validated outcomes. OBJECTIVE: To assess the 12-week efficacy of oral tetracyclines and a combination of clindamycin and rifampicin. METHODS: A prospective, international cohort study performed between October 2018 and August 2019. RESULTS: In total, 63.6% of the included 283 patients received oral tetracyclines, and 36.4% were treated with clindamycin and rifampicin. Both groups showed a significant decrease in International Hidradenitis Suppurativa Severity Score System from baseline (both P < .001). The Hidradenitis Suppurativa Clinical Response (HiSCR) was achieved in 40.1% and 48.2% of patients, respectively (P = .26). Patient characteristics or disease severity were not associated with the attainment of HiSCR or the minimal clinically important differences for the Dermatology Life Quality Index and pain. LIMITATIONS: Cohort study. Respectively, 23.9% and 19.4% of patients had to be excluded from the HiSCR analysis for the tetracycline and combination therapy group because of a low abscess and nodule count at baseline. CONCLUSION: This study shows significant efficacy of both tetracycline treatment and clindamycin and rifampicin combination therapy after 12 weeks in patients with hidradenitis suppurativa. No significant differences in efficacy were observed between the 2 treatments, regardless of disease severity.


Subject(s)
Clindamycin/administration & dosage , Hidradenitis Suppurativa/drug therapy , Rifampin/administration & dosage , Tetracyclines/administration & dosage , Adult , Clindamycin/adverse effects , Cohort Studies , Drug Combinations , Europe , Female , Humans , Male , Middle Aged , Prospective Studies , Rifampin/adverse effects , Tetracyclines/adverse effects , Treatment Outcome
12.
Dermatol Ther ; 33(4): e13570, 2020 07.
Article in English | MEDLINE | ID: mdl-32406149

ABSTRACT

Tinea capitis (TC) is a fungal infection of the hair and scalp. It mainly affects children, and treatment requires an extensive regimen including oral therapy, antifungal creams, and shampoo, as well as disinfection of fomites, bed linen, and clothes. Family members to patients with TC need prophylactic treatment to limit spread of the infection. Adherence to therapy in TC is time consuming, and the disease may cause psychosocial impairment to the caregivers. In this study, we performed interviews with parents to children with TC to identify factors related to treatment adherence and psychosocial implications from the parent's perspective. The interviews were performed and recorded at a dermatology outpatient clinic in Roskilde, Denmark (2018-2019). A total of 11 families agreed to participate in the study. The families had one to four affected children (age range: 1-14 years). We found that the key factors affecting adherence were the level of cooperation between the child and their parent, lack of symptoms in family members, and language barrier. The psychosocial well-being of parents was negatively affected due to fear of stigma and the time spent on treatment. Our study emphasizes the need for proper treatment instructions and psychosocial support of the parents by healthcare professionals.


Subject(s)
Tinea Capitis , Adolescent , Antifungal Agents/therapeutic use , Child , Child, Preschool , Humans , Infant , Pilot Projects , Scalp , Tinea Capitis/diagnosis , Tinea Capitis/drug therapy , Treatment Adherence and Compliance
13.
Acta Derm Venereol ; 100(9): adv00111, 2020 Apr 20.
Article in English | MEDLINE | ID: mdl-32207536

ABSTRACT

Superficial fungal infections have been known for hundreds of years. During the 20th century new diagnostic methods were developed and the taxonomy changed several times, which, unfortunately, resulted in many fungi having several names (synonyms). The taxonomy is important, as species-specific identification guides clinicians when choosing the most appropriate antifungal agent, and provides an indication of the source of infection (anthropophilic, zoophilic or geophilic). Traditional diagnostic tests (direct microscopy, culture and histopathology) are still widely used, but molecular-based methods, such as PCR, have many advantages, and increasingly supplement or replace conventional methods. Molecular-based methods provide detection of different genus/species spectra. This paper describes recent changes in dermatophyte taxonomy, and reviews the currently available diagnostics tools, focusing mainly on commercially available PCR test systems.


Subject(s)
Dermatomycoses , Antifungal Agents/therapeutic use , Dermatomycoses/diagnosis , Humans
14.
Dermatol Surg ; 46(7): 914-921, 2020 07.
Article in English | MEDLINE | ID: mdl-32049703

ABSTRACT

BACKGROUND: The possible connection between hidradenitis suppurativa (HS) patients undergoing surgery and higher complications/recurrences has been implied, but inconsistent results reported. OBJECTIVE: To assess the complication and recurrence rates for HS patients undergoing surgery and to evaluate whether known HS comorbidities and habits (smoking, obesity and diabetes) have an effect on the complication and recurrence rates. MATERIALS AND METHODS: A systematic review was conducted by 2 reviewers. PubMed and Embase were searched using a predefined search string created in collaboration between the authors and a librarian on January 23, 2019. RESULTS: Of the 271 references in the original search, 54 relevant articles were identified. This systematic review indicates an overall mean complication rate of 24% and a mean recurrence rate of 20.1% for HS patients undergoing surgery. CONCLUSION: No significant association between the known surgical risk factors and surgical complications-or recurrence rates in this patient group was found. This review revealed a lack of quality and quantity data in studying the complications/recurrences. The heterogeneity of the studies created limitations, and the presented mean complication/recurrence rates should be interpreted with the consequences thereof. It elucidates the need for better studies and a necessity for a standardized definition of postsurgical HS recurrence.


Subject(s)
Hidradenitis Suppurativa/surgery , Postoperative Complications/epidemiology , Humans , Recurrence
15.
Proc Natl Acad Sci U S A ; 114(15): 3933-3938, 2017 04 11.
Article in English | MEDLINE | ID: mdl-28348210

ABSTRACT

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in development and human disease, including cancer. It is currently thought that the four-point one, ezrin, radixin, moesin (FERM)-kinase domain linker, which contains autophosphorylation site tyrosine (Y) 397, is not required for in vivo FAK function until late midgestation. Here, we directly tested this hypothesis by generating mice with FAK Y397-to-phenylalanine (F) mutations in the germline. We found that Y397F embryos exhibited reduced mesodermal fibronectin (FN) and osteopontin expression and died during mesoderm development akin to FAK kinase-dead mice. We identified myosin-1E (MYO1E), an actin-dependent molecular motor, to interact directly with the FAK FERM-kinase linker and induce FAK kinase activity and Y397 phosphorylation. Active FAK in turn accumulated in the nucleus where it led to the expression of osteopontin and other FN-type matrix in both mouse embryonic fibroblasts and human melanoma. Our data support a model in which FAK Y397 autophosphorylation is required for FAK function in vivo and is positively regulated by MYO1E.


Subject(s)
Focal Adhesion Kinase 1/metabolism , Melanoma/metabolism , Myosins/metabolism , Skin Neoplasms/metabolism , Animals , Embryo Loss/genetics , Extracellular Matrix/metabolism , Extracellular Matrix/pathology , Female , Fibroblasts/metabolism , Fibronectins/metabolism , Focal Adhesion Kinase 1/chemistry , Focal Adhesion Kinase 1/genetics , Humans , Melanoma/pathology , Mesoderm/embryology , Mice, Mutant Strains , Myosin Type I , Myosins/chemistry , Myosins/genetics , Osteopontin/genetics , Osteopontin/metabolism , Phosphorylation , Pregnancy , Protein Domains , Skin Neoplasms/pathology , Tyrosine/metabolism
16.
Article in English | MEDLINE | ID: mdl-31383665

ABSTRACT

In recent years, cases involving terbinafine-resistant Trichophyton isolates have been reported increasingly, particularly in India. We present 14 cases of terbinafine treatment failure in Trichophyton-infected Danish patients due to acquired resistance. Patients infected with Trichophyton rubrum (n = 12) or Trichophyton interdigitale (n = 2) with elevated terbinafine MICs during 2013-2018 were included. Antifungal susceptibility testing (AFST) was performed following a modified EUCAST E.Def 9.3.1 method (5 days of incubation) with or without cycloheximide and chloramphenicol (CC) supplementation of the growth medium. The squalene epoxidase (SE) target gene was sequenced, and 3-dimensional enzyme homology modeling was performed. Most patients (12/14 [86%]) were male. The mean age was 53.5 years (range, 11 to 77 years). The mean duration of infections was 4.8 years at the time of resistance detection. Prior systemic terbinafine treatment was documented for all patients, and topical therapy for 62% (information was missing in one case). Overall, nine isolates (64%) displayed high terbinafine resistance (MICs, 4 to >8 mg/liter), while two (14%) displayed moderate (MICs, 1 to 2 mg/liter) and three (21%) displayed low (MICs, 0.125 to 0.25 mg/liter) terbinafine resistance compared with control isolates. MICs generated with or without CC supplementation were similar, but CC prevented contamination. Known and novel SE amino acid substitutions (F397L, L393F, L393S, F415S, H440Y F484Y, and I121M V237I) were detected in resistant but not control isolates. Three-dimensional homology modeling suggested a role of the novel I121M and V237I alterations. Terbinafine resistance has been detected in Denmark using a modified EUCAST method, which facilitated susceptibility testing of dermatophytes. Action is needed for this emerging public health problem.


Subject(s)
Antifungal Agents/pharmacology , Terbinafine/pharmacology , Trichophyton/drug effects , Trichophyton/pathogenicity , Adolescent , Adult , Aged , Antifungal Agents/therapeutic use , Child , Drug Resistance, Fungal/genetics , Fungal Proteins/genetics , Fungal Proteins/metabolism , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mutation/genetics , Squalene Monooxygenase/genetics , Squalene Monooxygenase/metabolism , Terbinafine/therapeutic use , Trichophyton/enzymology , Young Adult
18.
Mycoses ; 62(7): 584-587, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31050372

ABSTRACT

The zoophilic dermatophyte Trichophyton benhamiae has received attention due to increasing infections in human in recent years. Trichophyton benhamiae has been found on asymptomatic rodents from pet shops in several countries posing a potential risk for transmission to humans. The aim of this study was to determine the prevalence of positive dermatophyte cultures from rodents in Danish pet shops in order to clarify the magnitude of potential sources of zoophilic infections and to prevent further spread. Specimen sampling was performed in 17 Danish pet shops using the brush technique (MacKenzie technique). After incubation, cultures were sent to ITS DNA sequencing for molecular species identification. Pet shop employees were asked to fulfil a five-question survey regarding purchase and procedures of diseased animals. A total of 98 animals were sampled (N = 32 rabbits, N = 32 guinea pigs and N = 34 hamsters). Trichophyton benhamiae was found in 14/98 samples (14%); 12/32 guinea pigs (38%) were positive with T benhamiae, 2/34 (6%) hamsters and 0/32 rabbits (0%). We found that hamsters and particularly guinea pigs from Danish pet shops are common asymptomatic carriers of the dermatophyte T benhamiae. Although a larger study is warranted to test this postulate, and it raises the question if infection control measures should be implemented in pet shops.


Subject(s)
Carrier State/microbiology , Carrier State/veterinary , Pets/microbiology , Rodentia/microbiology , Tinea/veterinary , Trichophyton/isolation & purification , Animals , Carrier State/epidemiology , Cluster Analysis , DNA, Fungal/chemistry , DNA, Fungal/genetics , DNA, Ribosomal Spacer/chemistry , DNA, Ribosomal Spacer/genetics , Denmark/epidemiology , Phylogeny , Prevalence , Sequence Analysis, DNA , Tinea/epidemiology , Tinea/microbiology
20.
Pediatr Dermatol ; 36(3): 342-345, 2019 May.
Article in English | MEDLINE | ID: mdl-30834560

ABSTRACT

Successful management of toxic epidermal necrolysis (TEN) with tumor necrosis factor-α inhibitors has been described in adults. We present a case of a 7-year-old boy with infection-associated TEN, diagnosed by typical clinical and histopathological features, most likely caused by Mycoplasma pneumoniae. Treatment with a single dose of infliximab 5 mg/kg intravenously on day 5 after the onset of symptoms was followed by cessation of all blister formation over 3 days and complete resolution within a week. Sequelae were mild, consisting of postinflammatory hyperpigmentation and dry eyes.


Subject(s)
Dermatologic Agents/therapeutic use , Infliximab/therapeutic use , Stevens-Johnson Syndrome/drug therapy , Child , Humans , Male , Mycoplasma pneumoniae/isolation & purification , Stevens-Johnson Syndrome/microbiology , Stevens-Johnson Syndrome/pathology
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