Precision diagnostics in paediatric dermatology: Advancing management of tinea capitis through dermatophyte PCR.

BACKGROUND: Tinea capitis (TC) is the most frequent dermatophyte infection in children requiring systemic and topical treatment for several weeks. Traditionally, diagnosis and treatment monitoring were based on microscopic examination and fungal culture of scales and plucked hairs, which both have significant limitations. OBJECTIVES: To investigate the role of dermatophyte polymerase chain reaction (PCR) in the treatment of TC. METHODS: Scales and plucked hairs of children with TC were investigated by dermatophyte PCR, microscopic examination and fungal culture at baseline and during antifungal treatment. RESULTS: Seventeen children with TC were included. At baseline, sensitivity of PCR was 100% as compared to 60% and 87% for direct microscopy and fungal culture, respectively. Species identification by PCR and fungal culture was consistent in all cases. During follow-up, analysis of 38 samples under treatment showed a sensitivity of PCR, direct microscopy and fungal culture of 68%, 26% and 89% while specificity was 84%, 100% and 100%, respectively. PCR during therapy proved to be false-negative in six and false-positive in three instances. The latter turned negative after 4 weeks without further systemic treatment. CONCLUSIONS: Dermatophyte PCR is an excellent tool for baseline diagnostics of TC providing rapid and accurate results. Our findings suggest that due to the fast and reliable results, it may replace direct microscopy and fungal culture to confirm or exclude TC in children. In the treatment course, diagnostic accuracy and performance of PCR seem reduced as compared to fungal culture, limiting its value for treatment monitoring. Mycological cure ascertained by fungal culture should currently remain the therapeutic goal.

Epidemiological and clinical aspects of Trichophyton mentagrophytes/Trichophyton interdigitale infections in the Zurich area: a retrospective study using genotyping.

BACKGROUND: Trichophyton mentagrophytes (formerly Arthroderma vanbreuseghemii) and its clonal offshoot Trichophyton interdigitale, which are leading causes of dermatophytoses, have recently been recognized as two separate species. Over the last 20 years, several internal transcribed spacer (ITS) genotypes of Trichophyton mentagrophytes and Trichophyton interdigitale have been identified, some of which have specific characteristics and lead to typical clinical manifestations. OBJECTIVES: The aim of this study was to determine the current epidemiology of Trichophyton mentagrophytes and Trichophyton interdigitale genotypes in Switzerland, particularly in the Zurich area. METHODS: Consecutive cases diagnosed by ITS sequencing between 2009 and 2019 were retrospectively analysed. RESULTS: A total of 81 Trichophyton mentagrophytes and 81 Trichophyton interdigitale cases were investigated. T. mentagrophytes infections clearly differed from T. interdigitale infections by affecting younger and more frequently female patients, targeting almost exclusively head and body rather than feet and toenails, leading to inflammatory dermatophytosis and often requiring a combination of systemic and topical treatment. Seven different T. mentagrophytes genotypes (II*, III, III*, IV, VII, VIII and XXVI) were observed, with genotype XXVI being discovered in this study. Genotype III occurred most frequently (56% of all T. mentagrophytes cases) and affected predominantly children. Genotypes III* and VII led to inflammatory tinea in most cases. Four strains that proved to be terbinafine resistant belonged to the 'Indian genotype' VIII, which mostly caused tinea glutealis and inguinalis. CONCLUSION: Being able to distinguish between Trichophyton mentagrophytes and Trichophyton interdigitale is of paramount importance as the two species cause different clinical presentations. In addition, ITS genotyping allows recognizing sources of infection and potential terbinafine resistance. The latter needs to be confirmed by resistance testing or by sequencing part of the squalene epoxidase (SQLE) gene.

Cerebriform sebaceous nevus: a subtype of organoid nevus due to specific postzygotic FGFR2 mutations.

BACKGROUND: Postzygotic mutations in FGFR2 have been identified in mosaic forms of acne, keratinocytic epidermal nevi, nevoid acanthosis nigricans / rounded and velvety epidermal nevus and in two fetuses with papillomatous pedunculated sebaceous nevus (PPSN). OBJECTIVES: To determine the clinical and genetic characteristics of children with cerebriform, papillomatous and pedunculated variants of sebaceous nevi. METHODS: Infants diagnosed with sebaceous nevi characterized by a cerebriform, papillomatous and/or pedunculated morphology over a 10-year period (2010-2019) at three paediatric dermatology centres in Switzerland and France were included in this case series. Clinical and histological characteristics were assessed. Next-generation sequencing was used to assess for FGFR2 mutations. RESULTS: All nevi were located on the head, with a rounded or linear shape and a typical cerebriform, sometimes papillomatous and pedunculated, surface. No associated extracutaneous anomalies were found. Nevi harboured postzygotic mutations in the transmembrane domain of FGFR2 in 6/8 children (75%), either the known specific p.(Cys382Arg) mutation in 5 cases, or a novel mutation, p.(Val395Asp), in one. CONCLUSIONS: We found an exquisite genotype-phenotype correlation in these rare nevi, with specific postzygotic mutations in the transmembrane domain of FGFR2. As not all lesions were truly papillomatous and pedunculated, the term cerebriform sebaceous nevus (CSN) appears more suitable than PPSN to describe this entity. The cerebriform pattern of CSN is reminiscent of cutis gyrata, as seen in Beare-Stevenson syndrome, which is caused by closely related germline FGFR2 mutations. While clinically impressive, CSN seem to carry a good prognosis and a low risk for extracutaneous associations.

Skin-related quality of life in children and adolescents with congenital melanocytic naevi - an analysis of self- and parent reports.

BACKGROUND: Congenital melanocytic naevi (CMN) may affect patient quality of life (QoL) due to medical complications (development of malignant melanoma or involvement of the central nervous system), skin-related discomfort or psychosocial sequelae. OBJECTIVES: To analyse skin-related QoL in children and adolescents with CMN and to identify predictors of low QoL. METHODS: Worldwide recruitment of participants through patient support groups. Data collection through a Web-based survey. QoL was assessed using the Children's Dermatology Life Quality Index© (CDLQI). Demographic and CMN-related characteristics were examined as possible predictors of impaired QoL. RESULTS: A total of 135 proxy reports for children affected by CMN aged 4-18 years (M = 9.34 years, SD = 4.16 years) and 28 self-reports of adolescents aged 14-18 years (M = 16.3 years, SD = 1.2 years) were included. The mean CDLQI score was 4.00 (SD = 4.39) for proxy reports and 6.89 (SD = 5.85) for self-reports. Most parents (76%) reported 'no' or a 'small' impact, 19% a 'moderate' and 5% a 'very large' or 'extremely large' impact on their child's QoL. In self-reports, 46% of the adolescents reported 'no' or a 'small impact', 43% a 'moderate' and 11% a 'very large' or 'extremely large' impact. Visible CMN location, malignant melanoma and higher child's age were important predictors of QoL impairments. CONCLUSIONS: Most CMN have a modest effect on QoL. However, there is large variability with a significant proportion of adolescents experiencing a moderate-to-large impact on QoL in contrast to children. Healthcare professionals should be aware of the predictors of QoL in children with CMN.

Safe and effective use of alitretinoin in children with recalcitrant hand eczema and other dermatoses - a retrospective analysis.

BACKGROUND: Alitretinoin is a systemic retinoid licensed for use in adult patients suffering from chronic hand eczema recalcitrant to potent topical steroids. Experience with its use in childhood is lacking. OBJECTIVES: To report on the efficacy and safety of alitretinoin treatment in a cohort of children and adolescents with chronic hand eczema (CHE) and other inflammatory skin diseases. METHODS: We performed a retrospective chart review of all consecutive patients under the age of 18 years treated with alitretinoin at our paediatric skin centre. Physician's Global Assessment (PGA) was used as the primary outcome measure. RESULTS: Thirteen children (9 girls and 4 boys) were enrolled in this study. The median age at start of treatment with alitretinoin was 11.5 years (range 5.8-15.8 years). Nine children were diagnosed with CHE, two with severe atopic dermatitis (AD), and two with inherited ichthyosis [netherton syndrome (NS), autosomal recessive congenital ichthyosis (ARCI)]. Moderate to excellent response (PGA decrease of ≥1 point) was observed in 7 (78%) of the nine patients with CHE, one of the two patients with extensive AD and in the one patient with ARCI. In the remaining four subjects, no convincing effect was documented. Tolerability was overall very good. The most common adverse event was headache in 10 patients (77%) during the initiation of treatment, leading to interruption of therapy in one subject. CONCLUSIONS: Alitretinoin seems to be highly effective and safe for the treatment of paediatric CHE and should thus be considered in children with refractory disease under topical therapy. Larger studies are required to corroborate these findings.

Prospective evaluation of treatment response and disease reversibility of paediatric localized scleroderma (morphoea) to steroids and methotrexate using multi-modal imaging.

BACKGROUND: Paediatric localized scleroderma is a severe inflammatory disorder associated with tissue atrophy, often leading to disability. Assessing disease activity and response to treatment has always been challenging and remains an important difficulty in clinical practice. OBJECTIVES: To investigate prospectively the efficacy of systemic treatment with corticosteroids and methotrexate in children with localized scleroderma and the validity of infrared thermography, laser Doppler flowmetry and high-frequency ultrasound in assessing disease activity. METHODS: Children with localized scleroderma were prospectively treated with corticosteroids (initially pulsed IV methylprednisolone 30 mg/kg/day, maximum 500 mg/day and/or oral prednisolone 0.5-1 mg/kg/day) and methotrexate (15 mg/m2 weekly). Treatment response was evaluated using a clinical activity score. Skin temperature, blood flow, dermal thickness and dermal echogenicity of clinically active skin lesions were determined in relation to the unaffected contralateral site at baseline and after 3, 6, 12 and 18 months. Patient charts were later reviewed for long-term follow-up. RESULTS: Twenty-two patients were included [age 6.0 (0.2-14.4] years; female-to-male ratio 3.4 : 1) All responded well to therapy. Disease reversibility was demonstrated in the majority of children with partial resolution of skin sclerosis and regrowth of hair. Laser Doppler flowmetry and high-frequency ultrasound findings correlated with disease activity at baseline. Thermography had no added value in this cohort. The recurrence rate was 36% in the follow-up period. CONCLUSIONS: Corticosteroids and methotrexate are highly effective as first-line therapy in paediatric localized scleroderma, leading to partial reversal of skin manifestations. However, the recurrence rate is substantial and affected children require long-term follow-up. Laser Doppler flowmetry and high-frequency ultrasound correlate with disease activity in the acute phase and may assist decision-making in these patients.

[Acute skin infections and their imitators in children : A photo quiz]. / Akute Hautinfektionen und deren Imitatoren im Kindesalter : Ein Bilderquiz.

BACKGROUND: Skin infections account for 40% of emergency visits in pediatric dermatology. It is important to promptly recognize skin infections with potential complications and initiate treatment. However some characteristic skin findings may imitate skin infections and are often misdiagnosed. OBJECTIVES: To illustrate frequent pediatric skin infections and pitfalls in view of imitators and differential diagnoses. MATERIALS AND METHODS: A photo quiz is presented with the discussion of a selection of acute pediatric skin infections in comparison to their infectious or noninfectious differential diagnoses. RESULTS: The following infectious skin conditions and imitators are described and clinical clues for differentiation highlighted: eczema herpeticum and bacterial superinfection of atopic dermatitis; exanthematous hand, foot and mouth disease and varicella infection; erythema chronicum multilocularis and anular urticaria; Gianotti-Crosti syndrome and Gianotti-Crosti-like reaction; bacterial folliculitis of the scalp and kerion celsi and eosinophilic pustular folliculitis of the scalp; cutaneous Leishmaniasis and idiopathic facial aseptic granuloma; allergic and bacterial lymphangitis; bullous impetigo contagiosa and nonaccidental scalding. CONCLUSIONS: Careful anamnesis and skin examination with attention to the here illustrated differential diagnoses are essential to avoid pitfalls in the evaluation of acute pediatric skin infections.

[Congenital nevi in childhood]. / Kongenitale Nävi im Kindesalter.

Nevi represent congenital hamartomatous malformations of various components of the skin. The most common forms are congenital melanocytic nevi (CMN) and nevi of epithelial origin (epidermal and organoid nevi). Large CMN in particular can lead to severe complications and the management of those affected represents a challenge from birth. In contrast to previous assumptions, the risk of malignancy from CMN is considered to be relatively low however, this may be relevantly increased in certain situations. Possible extracutaneous symptoms in cases of central nervous system (CNS) involvement should not be underestimated and early imaging investigations are part of the routine diagnostic procedure. Surgical measures are still very important in the treatment of CMN but the indications must be weighed up for each individual case. Patients often experience marked stigmatization due to disfigurement by their birthmark and this needs to be taken into consideration for their treatment. The most common epithelial nevi are sebaceous nevi. In 2-13 % of cases additional tumors occur within this nevus and early surgical excision is indicated in most cases, not least for aesthetic reasons. If generalized spreading of epidermal nevi occurs, additional investigations are necessary to exclude associated ophthalmological, cardiac or neurological malformations.

The relative resistance of dengue-immune monkeys to yellow fever virus.

Dengue-immune rhesus monkeys were challenged with a South American and two African strains of yellow fever virus. Levels of viremia were reduced as compared with control nonimmunized monkeys. The results support the hypothesis that immunity to dengue in a human population acts as a barrier to establishment of yellow fever in that population.

The molecular weights of plasma and intestinal kallikreins in rats.

1. The molecular weights of kallikreins of rat intestine and rat plasma have been estimated using gel filtration. 2. Extracts of pooled tissue from rat jejunum, ileum, caecum and colon activated by autolytic processes gave a single peak of kallikrein activity with a molecular weights of 33000. 3. Acid-activated rat plasma gave two peaks of kallikrein activity with molecular weight of 125000 and 61500. 4. Rat intestinal tissue contains a kinin forming enzyme having a molecular weight similar to those of glandular kallikreins and different from those of the rat plasma kallikreins.

[Obtaining a reference pattern of rabbit brain thromboplastin]. / La obtención de un patrón de referencia de tromboplastina de cerebro de conejo.

Thromboplastin is a tissue extract used in the prothrombin time test (PT) necessary for oral anticoagulant control. The interlaboratory variability of the results of the PT test with thromboplastins of different tissue types, besides differences due to reporting PT in seconds or percentage, indicate the need for a standardized reference thromboplastin in order to express PT results on a common scale. The aim of the present work is to encourage the laboratory hospital either singly or in regional groups, to produce a standardized thromboplastin for their own use, to insure the control of oral anticoagulant therapy. Rabbit brain thromboplastin was prepared by Quick's technique. The reagent was calibrated against the international reference thromboplastin RBT/079, following the recommendations of the World Health Organization (WHO). Statistical analyses of the data were performed using an orthogonal regression. We obtained an international sensitivity index (ISI) of 2.177, a standard error of 0.0454 and a coefficient of variation of 2.09%. An international normalized ratio (INR) was also obtained for the conversion of measured PT to a common scale. The INNSZ thromboplastin is the first national reference preparation. With this reagent the introduction of an international scale for the control of oral anticoagulant therapy has become feasible in our country.

Neutralizing antibodies against certain viruses in the sera of residents of Trinidad, B. W. I

Blood samples taken from 1,055 indigenous residents of Trinidad B. W. I., were tested for neutralizing antibody against 17 different viral agents known or believed to be arthropod-borne, in 4,555 protection tests. Yellow fever, Ilheus and dengue are, or have been, on the basis of protection tests, presumably present, widespread, and common in Trinidad. A yellow fever outbreak occurred during the course of investigation in 1954. There is no evidence that Venezuelan equine encephalitis has been present on the island since the last reported outbreak in 1943. A small number of sera were found which neutralized St Louis encephalitis virus. No interpretation of this result is attempted. Although no human sera neutralized Eastern equine encephalitis virus, two different specimens of serum from one donkey neutralized the virus in two different tests. Interpretation of tests against Uganda S, West Nile, Semliki, Ntaya, and Japanese B is complicated by the possibility of interfering cross-immune reactions. All tests with Bwamba, Zika, Anopheles A, Western equine encephalites, and Bunyamwere viruses were negative. A provisional ecological zoning of the island is presented, based upon distribution of immunity against several viral agents (Summary)

Neutralizing antibodies against certain viruses in the sera of residents of Trinidad, B.W.I

Blood samples taken from 1,055 indigenous residents of Trinidad, B.W.I., were tested for neutralizing antibody against 17 different viral agents known or believed to be arthropod-borne, in 4,555 protection tests. Yellow fever, Ilheus and dengue are, or have, on the basis of protection tests, presumably present, widespread, and common in Trinidad. A yellow fever outbreak occurred during the course of investigations in 1954. There is no evidence that Venezuelan equine encephalitis has been present on the island since the last reported outbreak in 1943. A small number of sera were found which neutralized St. louis encephalitis virus. No interpretation of this result is attempted. Although no human sera netralized Eastern equine encephalitis virus, two different specimens of serum from one donkey neutralized the virus in two tests. Interpretation of tests against Uganda S, West Nile, Semliki, Ntaya, and Japanese B is complicated by the possibility of interfering cross-immune reactions. All tests with Bwamba, Zika, Anopheles A, Western equine encephalitis, and Bunyamwera viruses were negative. A provisional ecological zoning of the island is presented, based upon distribution of immunity against several Virus agents. (Summary).