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A letter to the editor is presented which discusses the treatment of well defined localized lesion of chromomycosis using carbon dioxide (CO2) laser vaporization.

A letter to the editor concerning a case report and discussion of differences from erythema dyschromicum perstans is presented.

Presents a letter to the editor about a study related to neurophysiological evidence for altered sensory function caused by storage of hydroxyethyl starch in cutaneous nerve fibres.

Surgery in malignant melanoma of the external ear often leads to substantial defects where reconstruction poses a difficult challenge. We describe an option of a one-step ear reconstruction after subtotal ear resection in malignant melanoma surgery. In a patient with a high-risk melanoma of the helical rim, a wide local excision was performed. Because of a metastasis-suspect lymph node in the parotid gland, surgery included asservation of the sentinel lymph node, neck dissection and parotidectomy. A complete reconstruction of the ear was achieved using a bilobed flap from the retroauricular and neck region with acceptable cosmetic and functional results by one-step surgery. One micrometastasis was detected in the nuchal region but not in the marked sentinel lymph node. An adequate one-step ear reconstruction as described may also be performed to the benefit of patients with high-risk melanomas, allowing early adjuvant therapy. [ABSTRACT FROM AUTHOR]

Aims : To assess and document the spectrum of histological appearances of persistent swellings which occur at injection sites following vaccination or allergen desensitization. Methods and results : Fourteen cases were studied. Four overlapping histological reaction patterns were evident. Ten cases showed at least focal fibrosis, fat necrosis and a mixed inflammatory cell infiltrate mainly in the subcutis, giving rise to the features of a non-specific septal and lobular panniculitis. The appearance of three cases, in addition to the non-specific panniculitis pattern, also included prominent lymphoid follicles with germinal centres and a prominent perifollicular infiltrate resembling a lymphoma (pseudolymphoma pattern). A single case mimicked lupus profundus, with a perivascular and periadnexal infiltrate in the dermis and hyaline fat necrosis. Three cases showed a predominantly palisaded histiocytic infiltrate surrounding eosinophilic necrobiosis, in a pattern closely resembling deep granuloma annulare or rheumatoid nodule. The remaining case partly showed this appearance, but in combination with panniculitis, thus demonstrating an overlap of patterns. A common feature in all 14 cases was the focal presence of histiocytes with abundant violaceous granular cytoplasm. These were shown to contain aluminium on energy dispersive X-ray microanalysis. Conclusion : Persistent swellings at injections sites show a variety of overlapping patterns, which mimic other conditions. Identification of characteristic histiocytes with violaceous granular cytoplasm is the key distinctive feature allowing the correct diagnosis to be reached. [ABSTRACT FROM AUTHOR]

Background: Autosomal‐recessive congenital ichthyosis (ARCI) is a heterogeneous group of ichthyoses presenting at birth. Self‐improving congenital ichthyosis (SICI) is a subtype of ARCI and is diagnosed when skin condition improves remarkably (within years) after birth. So far, there are sparse data on SICI and quality of life (QoL) in this ARCI subtype. This study aims to further delineate the clinical spectrum of SICI as a rather unique subtype of ARCI. Objectives: This prospective study included 78 patients (median age: 15 years) with ARCI who were subdivided in SICI (n = 18) and non‐SICI patients (nSICI, n = 60) by their ARCI phenotype. Methods: Quality of life (QoL) was assessed using the (Children's) Dermatology Life Quality Index. Statistical analysis was performed with chi‐squared and t‐Tests. Results: The genetically confirmed SICI patients presented causative mutations in the following genes: ALOXE3 (8/16; 50.0%), ALOX12B (6/16; 37.5%), PNPLA1 (1/16; 6.3%) and CYP4F22 (1/16; 6.3%). Hypo‐/anhidrosis and insufficient vitamin D levels (<30 ng/mL) were often seen in SICI patients. Brachydactyly (a shortening of the 4th and 5th fingers) was statistically more frequent in SICI (P = 0.023) than in nSICI patients. A kink of the ear's helix was seen in half of the SICI patients and tends to occur more frequently in patients with ALOX12B mutations (P = 0.005). QoL was less impaired in patients under the age of 16, regardless of ARCI type. Conclusions: SICI is an underestimated, milder clinical variant of ARCI including distinct features such as brachydactyly and kinking of the ears. Clinical experts should be aware of these features when seeing neonates with a collodion membrane. SICI patients should be regularly checked for clinical parameters such as hypo‐/anhidrosis or vitamin D levels and monitored for changes in quality of life. [ABSTRACT FROM AUTHOR]

Cannabinoid receptors mediate psychopharmacological, analgetic and immune functions of exogenous and endogenous cannabinoids. They are known to be localised in the central and peripheral nervous system as well as in immune tissues. Up to now, two cannabinoid receptors (CB) were cloned. Recent studies gave evidence for the presence of CB in the skin. To determine the precise localization of CB1 and CB2 in nerve fibers, epithelial cells of cutaneous appendage structures, epidermal keratinocytes and mast cells, we performed an immunohistochemical study in a series of normal human skin and mastocytosis. CB1 and CB2 immunoreactivity could be observed in cutaneous sensory and autonomic nerve fibers, mast cells, epidermal keratinocytes, epithelial cells of hair follicles, sebocytes, and eccrine sweat glands. Interestingly, in epidermal keratinocytes, hair follicle and sebaceous glands, CB1 and CB2 were distributed in a complementary fashion. Our study confirmed previous reports describing that cutaneous application of the selective CB1 and CB2 agonist HU 210 significantly reduced capsaicin-induced burning pain as well as histamine-evoked itch. Together, these findings suggest that CB act as inhibitory neuronal receptors diminishing excitation of skin nerves and release of neuropeptides. This has an interesting implication on the therapeutical use of cannabinoid agonists as antipruritic and analgetic agents. In conclusion, both cannabinoid receptors are widely distributed in the skin suggesting a central role for this receptor, e.g. in epithelial cell differentiation as well as in inhibition of nociceptive sensations. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa acquisita (EBA) is an autoimmune bullous disease with frequent ocular involvement, but visual loss is rare. In contrast, EBA patients with predominant IgA autoantibodies more frequently develop severe ocular involvement, which tends to be refractory to therapy. We report two patients with ‘IgA–EBA’ with ocular involvement. Both initially presented with a generalized bullous disease, and direct immunofluorescence microscopy demonstrated IgA in the basement membrane zone of the skin, and in the conjunctiva and cornea of patient 1. On salt-split patient skin, IgA was found predominantly on the dermal side of the artificial split in both patients. Direct immunoelectron microscopy demonstrated IgA below the lamina densa in close association with the anchoring fibrils in both patients. In patient 1, who had a prolonged course of the disease, the skin disorder responded well to treatment with cyclosporin, but the ocular involvement ended in bilateral blindness despite repeated surgical treatment. In patient 2, the blister formation and scarring conjunctivitis was stopped by a combination of prednisolone and colchicine. These patients show that in subepithelial blistering diseases, early delineation of disease nosology is critical to detect subtypes with severe ocular involvement such as ‘IgA–EBA’. In addition, colchicine may be a valuable alternative in the treatment of EBA with ocular involvement. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 37-year-old white woman who was presented with progressive skin wrinkling and an aged appearance. She was diagnosed with membranoproliferative glomerulonephritis one year before and she received oral corticosteroids in combination with torasemide. Her specimen revealed rarefication of elastic fibres in the papillary and reticular dermis confirming the diagnosis of cutis laxa acquisita (CLA).

Background Dermatophytosis is a very common skin infection with a broad clinical spectrum. Biopsies are often used to confirm the diagnosis, especially when the clinical presentation is unusual. Not uncommonly, organisms are hard to find even with periodic acid-Schiff stains. Polymerase chain reaction ( PCR) for dermatophytes can be used in such cases. Objectives To test a new PCR assay allowing species identification of dermatophytes on paraffin-embedded biopsies, and to reassess histopathological criteria for diagnosis of dermatophytosis. Methods In total, 121 biopsies of 92 patients with clinical suspicion of tinea were included. In 42 samples the clinical diagnosis had been confirmed histopathologically, and in 79 no fungal elements had been identified. PCRs targeting the internal transcribed spacer ( ITS)2 region of dermatophytes were performed on the biopsies with subsequent sequencing. Sections were reassessed for the presence/absence of hyphae/spores, pattern and composition of infiltrate, and epidermal/follicular changes. Patient charts were reviewed for clinical data. Results The new ITS2 PCR assay detected 94% of the dermatophyte infections (compared with 79% identified by microscopy). Trichophyton rubrum was the dominant species (89%), and other species identified were Trichophyton verrucosum (2%), Microsporum canis (4%), Epidermophyton floccosum (2%) and Trichophyton interdigitale (4%). In particular, infections with T. interdigitale and manifestations with prominent spongiosis were not diagnosed histologically. Intracorneal neutrophils, which have been emphasized as a histopathological clue to dermatophytosis, were present in only 46% of PCR-positive samples. Conclusions Molecular species identification of dermatophytes via ITS2 PCR can easily be implemented in a routine dermatopathology setting. It is fast and highly specific and improves the sensitivity of histopathological diagnosis of dermatophytosis. [ABSTRACT FROM AUTHOR]

Background The prognostic and therapeutic features of scleredema are poorly documented. Objectives To describe the characteristics of patients with scleredema regarding demographics, clinical characteristics, comorbidities, therapeutic interventions and course. Methods We conducted a retrospective multicentre study. Results We identified 44 patients (26 men).The mean age at diagnosis was 53.8 years. The most common associated disorders were endocrine/metabolic diseases including 30 patients suffering from diabetes, mostly type 2 diabetes. Monoclonal gammopathies were confirmed in five cases. A preceding respiratory tract infection was not a feature. Treatments with different combination or sequential modalities were used with variable results. Phototherapy (UVA1 or PUVA) was the treatment associated with higher, although partial response. Systemic corticosteroids and immunosuppressive drugs were reserved to patients with severe disease in whom phototherapy had failed or for patients with multiple myeloma. Forty-one patients were followed up (mean period: 32.2 months).Thirty-nine patients are alive, 30 with and 9 without skin disease. Two patients died of cardiovascular complications due to myeloma and severe diabetes. Conclusions Scleredema is a chronic debilitating disease associated with diabetes and metabolic syndrome, unresponsive to various treatments but not necessarily a life-threatening condition. Although there is no definitive treatment, phototherapy should be attempted first. Treatment of primary disease including strict glycaemic control combined with physical therapy should be also employed. [ABSTRACT FROM AUTHOR]

Background Northern spread of sandflies and Leishmania spp. has been observed in Europe. Diagnosis can be difficult owing to the various clinical manifestations. Species identification is important for patient management and therapy. Molecular diagnostics is increasingly used for pan-Leishmania detection but species identification remains challenging in formalin-fixed material. Objectives To apply cytochrome b (cytb) polymerase chain reaction (PCR) and sequencing for identification of Leishmania species on formalin-fixed, paraffin-embedded (FFPE) skin biopsies; and to identify species-specific histological patterns. Methods Sixty-nine biopsies (48 patients) diagnosed with leishmaniasis based on the presence of amastigotes in the tissue (n = 41) or granulomatous infiltrates with positive pan-Leishmania real-time PCR (n = 28) were analysed with cytb PCR, sequencing and phylogenetic analysis. Histological sections were analysed; epidemiological data were collected. Results Cytb PCR identified Leishmania in all specimens: L. infantum (79%), L. major (8%), L. panamensis (4%), L. tropica (4%), L. killicki (2%) and L. aethiopica (2%). Of the detected species 95% were endemic to the country in which the infection was acquired. Amastigotes were found in 59%. Infiltrates were mainly tuberculoid granulomatous (65%), interstitial (15%) and sarcoidal (10%). Pseudolymphomatous features and pseudocarcinomatous hyperplasia were more common in L. major infections than in L. infantum (P < 0·01). Conclusions Cytb PCR and sequencing is a fast, reliable and sensitive assay for identification of Leishmania spp. in FFPE biopsies. Leishmania infantum is the main cause of cutaneous leishmaniasis in Germany. Tuberculoid granulomas, other types of granulomas and pseudolymphomatous infiltrates may be encountered; the latter being indicative of infection with L. major. [ABSTRACT FROM AUTHOR]

Background Lyme borreliosis has a broad spectrum of clinical presentations involving the skin, joints and nervous system. The variable manifestations have been attributed to different Borrelia genospecies but genotyping required culture or fresh tissue. However, in dermatology practice, formalin-fixed paraffin-embedded biopsies are used for dermatopathological examination. Polymerase chain reaction ( PCR) for Borrelia burgdorferi sensu latu has been established on such specimens, but studies attempting genotyping of subspecies or strains are lacking. Objectives To adapt PCR assays for genotyping of Borrelia using paraffin-embedded biopsies, to identify Borrelia genospecies and to compare clinicopathological features of different genospecies. Methods Eighty-two paraffin-embedded biopsies from 68 patients, with erythema migrans, acrodermatitis chronica atrophicans, lymphocytoma cutis or tick bite reactions, were studied with assays targeting the intergenic spacer ( IGS), ospA and ospC, followed by sequencing and phylogenetic analysis. Clinicopathological data were analysed comparing different Borrelia genospecies. Results Genotyping by IGS, ospA and ospC was successful in 85% of patients (91% B. afzelii, 7% B. garinii, 2% B. bavariensis). ospA serotyping identified type 2 (90%), type 3 (8%) and type 4 (2%). ospC- PCR was positive in 40% of the patients revealing 12 different groups, noninvasive forms being seen only in tick bite reactions and erythema migrans. No major clinicopathological differences could be identified between the genospecies, but neural inflammation and arthralgia were seen more often in lesions caused by invasive ospC strains. Conclusions Genotyping of Borrelia can be easily implemented in a routine dermatopathology setting, especially as a fast method to confirm early cutaneous borreliosis. Genotyping could also enable earlier treatment of patients infected with invasive strains. [ABSTRACT FROM AUTHOR]

Background Ichthyosis vulgaris ( IV) is caused by loss-of-function mutations in the profilaggrin ( FLG) gene. Filaggrin drives complex interrelated functions, with strategic roles in establishing structural and chemical barrier function, hydration of the skin and maintaining epidermal homeostasis. Data on the effect of FLG mutations on epidermal barrier function in IV are very scarce. Objectives A primary aim of this study was to determine in vivo characteristics of epidermal permeability barrier function such as transepidermal water loss ( TEWL), skin hydration and skin surface pH in homozygous or compound heterozygous ( FLG−/−) and heterozygous ( FLG+/−) subjects with IV. Methods We evaluated a cohort of 15 patients with IV, analysed epidermal ultrastructure and investigated epidermal barrier function by measurement of TEWL, skin surface pH and skin hydration. Mutations were screened by restriction enzyme analysis and/or complete sequencing. Ten patients were homozygous or compound heterozygous ( FLG−/−), while five patients were heterozygous ( FLG+/−). Twenty healthy individuals served as controls. Results In FLG−/− subjects, a moderate increase of TEWL from 5.41 ± 0.32-7.54 ± 0.90 g/m2h ( P < 0.03) and a moderate decrease of skin hydration from 29.20 ± 1.96 to 20.17 ± 3.60 ( P < 0.05) in comparison with the control group were observed. Changes in skin surface pH were not significant. FLG+/− subjects did not suffer from significant changes in all variables. Conclusions A complete, but not a partial deficiency is associated with moderate changes in TEWL and skin hydration, revealing surprisingly only a mild disturbance of the epidermal permeability barrier function. [ABSTRACT FROM AUTHOR]

Summary Background Benign mucinous metaplasia of the genitalia (BMM) is a rare condition typified by cells with foamy mucinous cytoplasm. Differential diagnoses include extramammary Paget disease (PD) and human papillomavirus (HPV)-induced vulval intraepithelial neoplasia (VIN) with mucinous differentiation. Objectives To characterize histopathological and immunohistochemical features of BMM and to forge criteria for differentiation from PD and VIN with mucinous differentiation. Methods Eight biopsy specimens of BMM were stained with haematoxylin and eosin, periodic acid-Schiff and alcian blue, and for cytokeratin (CK) 7, CK10, CK14, CK20, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), S100, gross cystic disease fluid protein-15 (GCDFP-15), lysozyme and Ki67 and compared with PD. Polymerase chain reaction was performed in order to identify HPV-specific DNA. Results BMM showed mucin deposition in superficial epithelial layers ranging from numerous large goblet cells to subtle deposits. The epithelium often showed polygonal (squamoid) or cuboidal differentiation while columnar differentiation was an inconsistent feature. A band-like inflammatory infiltrate was consistently present. Metaplastic epithelium consistently expressed CK7, CEA and EMA either in the entire epithelium or in a superficial band, while CK14, CK10, GCDFP-15 and lysozyme were largely not expressed, and staining for CK20 and S100 was negative. Comparison with PD demonstrated similar staining characteristics, but in a scattered pattern of mucinous cells within preserved squamous epithelium and not in a band-like pattern as in BMM. Nuclear pleomorphism and Ki67-positive mucinous cells in superficial epithelial layers were seen only in PD; GCDFP-15 and/or lysozyme were expressed in the majority of cases of PD. No evidence of HPV-specific DNA was found in BMM. Conclusions The spectrum of changes in BMM is distinctive, and BMM can be differentiated with surety from both PD and VIN with mucinous differentiation. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

To cite this article: Sachse F, Becker K, von Eiff C, Metze D, Rudack C. Staphylococcus aureus invades the epithelium in nasal polyposis and induces IL-6 in nasal epithelial cells in vitro. Allergy 2010; 65: 1430-1437. Background: Staphylococcus aureus has been associated with chronic rhinosinusitis with nasal polyps (CRSwNP) pathogenesis but its role is still controversially discussed. Here, we demonstrate S. aureus detection in the mucosa of CRSwNP. In addition, intracellular residency of S. aureus in nasal polyp epithelial cells (NPECs) and its capability to induce TH-2 cytokines were analyzed in vitro. Methods: Staphylococcus aureus detection in CRSwNP ( n = 25), CRS without polyps (CRSsNP, n = 5), and turbinate mucosa (TM, n = 10) was performed by peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) and microbial cultivation from tissue biopsies. Intracellular residency was examined by intracellular persistence assay and electron microscopy. IL-6 and IL-13 responses to S. aureus infection and supernatants were quantified by ELISA. Results: Peptide nucleic acid-fluorescence in situ hybridization positive bacterial cells were significantly increased in the epithelium of CRSwNP (17/25) compared to CRSsNP (0/5) and TM (1/10). Good concordance of PNA-FISH results and S. aureus cultivation was found applying Cohen's κ for CRSwNP (κ = 0.841) and TM (κ = 1.0). Intracellular persistence assay with S. aureus strain Newman and its corresponding small-colony variant mutant strain III33 demonstrated intracellular survival and replication of S. aureus within NPECs. Both S. aureus strains significantly induced IL-6 but not IL-13 in infected NPECs and in NPECs challenged with corresponding staphylococcal supernatants. Conclusion: Invasion of the epithelium by S. aureus was a phenomenon seen predominantly in CRSwNP. Regardless of an intra- or extracellular localization in the epithelium, S. aureus is capable to induce IL-6 synthesis in vitro and thus may contribute to the TH-2 cytokine pattern in CRSwNP. [ABSTRACT FROM AUTHOR]

Background Lupus erythematosus tumidus (LET) is a rare disease which was first described in 1909 but has not always been considered as a separate entity of cutaneous lupus erythematosus (CLE) in the international literature. Objectives To compare characteristic features of different subtypes of CLE and to analyse whether LET can be distinguished as a separate entity in the classification system of the disease. Methods The study involved 44 patients with CLE, including 24 patients with LET, 12 with discoid lupus erythematosus (DLE) and eight with subacute CLE (SCLE), from two centres in Germany. A core set questionnaire and an SPSS database were designed to enable a consistent statistical analysis. Results Location of skin lesions did not differ significantly between the CLE subtypes; however, the activity score was significantly lower in LET than in DLE ( P < 0·01), and the damage score was significantly lower in LET than in SCLE ( P < 0·01) and DLE ( P < 0·01). Photosensitivity and antinuclear antibodies were confirmed to be different in LET compared with SCLE and DLE but without statistical significance. Moreover, histological analysis of skin biopsy specimens showed that abundant mucin deposition is significantly more present in LET compared with SCLE ( P < 0·01) and DLE ( P < 0·01) while prominent interface dermatitis and alteration of hair follicles were absent in LET. Conclusions Several significant differences were found between LET and other subtypes of CLE with regard to clinical, histological and laboratory parameters. These data strongly indicate that LET should be defined as a separate entity in the classification of CLE. [ABSTRACT FROM AUTHOR]

Background Ichthyosis vulgaris (IV) is a genetic disorder with a prevalence of 1 : 250–1000 caused by filaggrin ( FLG) mutations, which also predispose to atopic diseases. Objectives To study the genotype/phenotype relationship in IV and to analyse whether the suggested skin barrier defect is associated with differences of epidermal dendritic cells. Patients/methods We evaluated a cohort of 26 German patients with IV, established an IV severity score and analysed epidermal ultrastructure, histology, filaggrin and CD1a antigens. Mutations were screened by restriction enzyme analysis. Particular sequencing techniques allowed the complete FLG analysis to reveal novel mutations. Results The combined null allele frequency of R501X and 2282del4 was 67·3%. Patients also showed the mutations S3247X and R2447X as well as five novel FLG mutations: 424del17 and 621del4 (profilaggrin S100 domain), 2974delGA (repeat 2), R3766X (repeat 101) and E4265X (repeat 102). Their combined allele frequency in controls was < 0·7%. No mutation was found in one IV patient, all in all ∼27% were heterozygous, and the majority (∼69%) showed two null alleles. The IV severity score and ultrastructure showed a significant correlation with genotypes. Interestingly, CD1a cell counts showed a significant difference between nonatopic and atopic IV patients both with eczema and without eczema. Conclusions We confirm that the mutations R501X and 2282del4 represent the most frequent genetic cause in German IV patients. The novel mutations are probably population and family specific. The observed differences of CD1a cells support the hypothesis that there is a barrier defect that predisposes to atopic manifestations, possibly independent of atopic eczema. [ABSTRACT FROM AUTHOR]

We report a 72-year-old male patient with a nodular malignant melanoma that was associated with focal suprabasal acantholysis (FSA). This phenomenon, which is regarded as an incidental finding by dermatopathologists, may be associated with inflammatory and also neoplastic skin diseases. Haematoxylin and eosin stained sections from an erythematous plaque surrounding the patient’s tumour showed FSA, direct immunofluorescence (DIF) and indirect immunofluorescence (IIF) on normal human skin, monkey oesophagus and rat urinary bladder were negative. On electron microscopy few desmosomes could be detected in the basal cell layer of the acantholytic areas and there was a nearly complete loss of these structures in the spinous cell layer. Only remnants of cytoplasmic plaques and keratin filaments could be observed in those areas. In contrast, adherens junctions appeared to be well preserved. An enzyme-linked immunosorbent assay (ELISA) using recombinant fusion proteins as antigens did not show circulating autoantibodies against desmoglein 1 (Dsg1) or desmoglein 3 (Dsg3). In contrast, immunoblotting revealed autoantibodies directed against keratinocyte antigens with a molecular weight of 85 kDa and 250 kDa, the first band corresponding to the molecular weight of comigrating plakoglobin. Immunoprecipitation with patient serum also revealed a 85-kDa band. We conclude that these autoantibodies, probably in conjunction with cofactors produced by the tumour, could play a part in the pathogenesis of this variant of FSA, for which we propose the term ‘localized paraneoplastic pemphigus.’. [ABSTRACT FROM AUTHOR]

Microbial growth is central to soil carbon cycling. However, how microbial communities grow under climate change is still largely unexplored. Here we use a unique field experiment simulating future climate conditions (increased atmospheric CO 2 and temperature) and drought concomitantly and investigate impacts on soil microbial activity. We trace 2 H or 18 O applied via water-vapor exchange into membrane (and storage) fatty acids or DNA, respectively, to assess community- and group-level adjustments in soil microbial physiology (replication, storage product synthesis, and carbon use efficiency). We show that, while bacterial growth decreases by half during drought, fungal growth remains stable, demonstrating a remarkable resistance against soil moisture changes. In addition, fungal investment into storage triglycerides increases more than five-fold under drought. Community-level carbon use efficiency (the balance between anabolism and catabolism) is unaffected by drought but decreases in future climate conditions, favoring catabolism. Our results highlight that accounting for different microbial growth strategies can foster our understanding of soil microbial contributions to carbon cycling and feedback on the climate system., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The occurrence of pruritus in psoriasis was previously underestimated but is a significant burden. Secukinumab (SEC), a monoclonal anti-interleukin-17A antibody, efficiently controls signs of psoriasis, but the effect on pruritus and cutaneous neuroanatomy remained unknown. The primary objective of this study (NCT02362789) was to evaluate the superiority of SEC treatment vs placebo on pruritus intensity (visual analogue scale; VAS). Furthermore, the treatment-dependent course of pruritus in association with absolute Psoriasis Area Severity Index (PASI) score, as well as cutaneous histopathology and neuroanatomy, was assessed. Open-label SEC 300 mg s.c. was administered regularly until week 16. Patients who reached a ≥ 98% PASI reduction (PASI ≥ 98) were randomized to receive either placebo or SEC up to week 32. Punch biopsies were collected from lesional psoriatic (baseline, weeks 16 and 32) and non-lesional (baseline) skin for histopathological and neuroanatomical analyses. VAS scores improved significantly after open-label SEC treatment but relapsed upon placebo (29.92 ± 33.8) compared with SEC (12.30 ± 22.6; p = 0.036). After SEC-dependent improvement in PASI, histopathology, marker expression and neuroanatomy, relapse was observed with treatment discontinuation in all parameters except neuroanatomy. SEC was superior to placebo by efficiently controlling reduced pruritus intensity, clinically normalizing skin lesions, and reversing histopathological abnormalities. The neuroanatomy recovered upon SEC and remained stable even after withdrawal.

Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: S. A. Braun, E. Bierhoff und D. Metze geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien. The supplement containing this article is not sponsored by industry.

Background: Excision and histological examination of cutaneous neoplasms are very common diagnostic and therapeutic procedures in dermatological practice. There are often discrepancies between tissue seize in vivo and after histopathological work-up. This may raise questions according to tumor sizes or safety margins., Methods: To investigate the effect of excision and histological processing on the properties of cutaneous neoplasms in real-life 401 specimens in 324 patients were prospectively investigated. Delineated excision margins of cutaneous neoplasms were documented prior to (T0) and post excision (T1). Length, width and thickness were measured after ≥48 h of formalin fixation (T2) and after sectioning (T3) on final histological slices. Accompanying parameters such as patient age, gender, anatomical site, and tumor entity were evaluated., Results: All post-processed tissue exhibited a significant (P<0.001) median (interquartile range) reduction in length, width and thickness of 21.0% (9.5-30.0), 30.7% (20.0-40.0), and 28.0% (4.8-46.7), respectively, irrespective of site, patient age or tumor entity. Maximum median (IQR) reduction for the length and the width was observed right after excision (17.0% [4.3-25.0] and 14.0% [11.1-28.6] reduction). No significant median (IQR) tissue changes between T1 and T2 were observed (length: 4.8% (-4.3-13.3); width: 0% (-17.6-11.1); thickness 0% (-32.0-20.0). Subgroup analyses showed significantly greater tissue shrinkage in younger patients and for tissue sample sites (trunk or lower extremities)., Conclusions: Most relevant shrinkage of cutaneous samples occurs right after excision. Age- and site-depended tissue contractility can influence these effects. Formalin fixation does not affect tissue shrinkage. Smaller tissue sizes on histopathological reports are to be expected.

Hydroxychloroquine is used for treatment of inflammatory diseases. It is considered to have few adverse effects. We report on a woman who developed a severe skin rash after intake of hydroxychloroquine, which she received for treatment of her lichen planopilaris. Based on the clinical, laboratory and histological findings the diagnosis of a drug reaction with eosinophilia and systemic symptoms (DRESS)-like drug reaction was established. Our case illustrates that hydroxychloroquine can lead to severe adverse effects in rare cases and that patients receiving this drug must be thoroughly informed., (© 2024. The Author(s).)

Soil microorganisms control the fate of soil organic carbon. Warming may accelerate their activities putting large carbon stocks at risk of decomposition. Existing knowledge about microbial responses to warming is based on community-level measurements, leaving the underlying mechanisms unexplored and hindering predictions. In a long-term soil warming experiment in a Subarctic grassland, we investigated how active populations of bacteria and archaea responded to elevated soil temperatures (+6°C) and the influence of plant roots, by measuring taxon-specific growth rates using quantitative stable isotope probing and 18 O water vapor equilibration. Contrary to prior assumptions, increased community growth was associated with a greater number of active bacterial taxa rather than generally faster-growing populations. We also found that root presence enhanced bacterial growth at ambient temperatures but not at elevated temperatures, indicating a shift in plant-microbe interactions. Our results, thus, reveal a mechanism of how soil bacteria respond to warming that cannot be inferred from community-level measurements.

Eggplant (Solanum melongena) suffers severe losses due to a multi-insecticide-resistant lepidopteran pest, shoot and fruit borer (SFB, Leucinodes orbonalis). Heavy and combinatorial application of pesticides for SFB control renders eggplant risky for human consumption. We observed that gravid SFB females do not oviposit on Himalayan eggplant variety RC-RL-22 (RL22). We hypothesized that RL22 contained an antixenosis factor. Females' behavior indicated that the RL22 cue they perceived was olfactory. To identify it, leaf volatile blends of seven eggplant varieties were profiled using solid phase microextraction and gas chromatography mass spectrometry. Seven RL22-specific compounds were detected in the plant headspace. In choice assays, oviposition deterrence efficacies of these candidate compounds were independently tested by their foliar application on SFB-susceptible varieties. Complementation of geraniol, which was exclusively found in RL22, reduced oviposition (> 90%). To validate geraniol's role in RL22's SFB-deterrence, we characterized RL22's geraniol synthase and silenced its gene in planta, using virus-induced gene silencing. Geraniol biosynthesis suppression rendered RL22 SFB-susceptible; foliar geraniol application on the geraniol synthase-silenced plants restored oviposition deterrence. We infer that geraniol is RL22's SFB oviposition deterrent. The use of natural compounds like geraniol, which influence the chemical ecology of oviposition, can reduce the load of hazardous synthetic larvicides., (© 2023 The Authors. New Phytologist © 2023 New Phytologist Foundation.)

Background: Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR., Material and Methods: We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied. Immunohistochemistry (IHC) and RT-PCR was performed in skin biopsies., Results: After a careful review of the cases, 15 were found to be dermatosis not related to COVID-19, while the rest of the lesions could be classified according to their clinical characteristics as vesicular (4), maculopapular eruptions (41), urticariform (9), livedo and necrosis (10) and pernio-like (5). Although histopathological features were similar to previously reported results, we found two previously unreported findings, maculopapular eruptions with squamous eccrine syringometaplasia and neutrophilic epitheliotropism. IHC showed in some cases endothelial and epidermal staining but RT-PCR was negative in all the tested cases. Thus, direct viral involvement could not be demonstrated., Conclusions: Despite presenting the largest series of confirmed COVID-19 patients with histopathologically studied skin manifestations, direct viral involvement was difficult to establish. Vasculopathic and urticariform lesions seem to be those more clearly related to the viral infection, despite IHC or RT-PCR negative results failed to demonstrate viral presence. These findings, as in other dermatological areas, highlight the need of a clinico-pathological correlation to increase knowledge about viral involvement in COVID-19 skin-related lesions., (Copyright © 2023. Publicado por Elsevier España, S.L.U.)

Climate change increases the frequency and intensity of drought events, affecting soil functions including carbon sequestration and nutrient cycling, which are driven by growing microorganisms. Yet we know little about microbial responses to drought due to methodological limitations. Here, we estimate microbial growth rates in montane grassland soils exposed to ambient conditions, drought, and potential future climate conditions (i.e., soils exposed to 6 years of elevated temperatures and elevated CO 2 levels). For this purpose, we combined 18 O-water vapor equilibration with quantitative stable isotope probing (termed 'vapor-qSIP') to measure taxon-specific microbial growth in dry soils. In our experiments, drought caused >90% of bacterial and archaeal taxa to stop dividing and reduced the growth rates of persisting ones. Under drought, growing taxa accounted for only 4% of the total community as compared to 35% in the controls. Drought-tolerant communities were dominated by specialized members of the Actinobacteriota, particularly the genus Streptomyces. Six years of pre-exposure to future climate conditions (3 °C warming and + 300 ppm atmospheric CO 2 ) alleviated drought effects on microbial growth, through more drought-tolerant taxa across major phyla, accounting for 9% of the total community. Our results provide insights into the response of active microbes to drought today and in a future climate, and highlight the importance of studying drought in combination with future climate conditions to capture interactive effects and improve predictions of future soil-climate feedbacks., (© 2023. Springer Nature Limited.)

Monkeypox (mpox), a former rare viral zoonosis, has increasingly made it into the public eye since the major outbreak that started in May 2022. Mpox presents with skin lesions that change over time and go through different stages (macular, papular, pustular, and early and late ulceration). In this study, we evaluated skin biopsies of all stages. Therefore, five biopsies from four patients were analyzed histologically, immunohistochemically with anti- Vaccinia virus antibodies, and electron-microscopically. Notably, the early macular stage only showed subtle viropathic changes; it did not express of Orthopoxvirus proteins in immunohistochemistry and therefore can easily be missed histologically. In later stages, immunohistochemistry with anti- Vaccinia virus antibodies might be useful to distinguish mpox from differential diagnoses such as herpes virus infections. In the ulcerative stages, the identified occlusive vasculopathic changes could be an explanation for the severe pain of the lesions reported by some patients. Despite the small number of samples examined, our analysis suggests that the histological findings of mpox are highly dependent on the stage of the biopsied lesion. Therefore, knowledge of all different stages of histology is necessary to reliably diagnose mpox histologically, especially when molecular testing is not available.

Background: Hyperkeratosis lenticularis perstans (HLP), also known as Flegel disease, is a rare skin disease presenting with asymptomatic small hyperkeratotic papules. The lesions often appear on the dorsal feet and lower legs, and typically develop after the fourth decade of life. A genetic basis for HLP is suspected; however, so far no gene defect linked to the development of HLP has been identified., Objectives: We aimed to identify the genetic cause of HLP., Methods: For mutational analysis we studied a cohort of five patients with HLP using next-generation sequencing (NGS). We used DNA -extracted from fresh skin biopsies alongside ethylenediamine tetraacetic acid (EDTA) blood samples from two patients, and formalin-fixed -paraffin-embedded skin biopsy material from three patients. In addition, immunofluorescence staining of HLP lesions from four patients was investigated., Results: In all samples from the five patients with HLP we identified by NGS rare variants in the SPTLC1 gene. In four patients we detected small deletions/frameshift variants and in one patient a splicing variant, predicted to disturb the splicing process. In blood samples the detected variants were heterozygous with an allele frequency of 49% and 50%, respectively. In skin biopsies the allele frequency was within the range of 46-62%. Immunofluorescence staining revealed reduced SPTLC1 protein levels in skin of patients., Conclusions: Our findings suggest that pathogenic variants in the SPTLC1 gene are the underlying genetic cause of HLP. Of note, the identified variants were either frameshift- or splicing variants probably leading to nonsense-mediated mRNA decay and thus reduced SPTLC1 protein levels. We conclude that diminished SPTLC1, the key enzyme in sphingolipid biosynthesis, leads to the development of HLP, which highlights the sphingolipid pathway as a new therapeutic target., Competing Interests: Conflicts of interest: The authors declare they have no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ingenol mebutate (IM) is highly effective in the treatment of human papillomavirus (HPV)-induced anogenital warts (AGW) leading to fast ablation within hours. However, the exact mode of action is still largely unknown. We performed dermoscopy, in vivo confocal microscopy (CLM), histology, immunohistochemistry, and immunofluorescence to gain insights in mechanisms of IM treatment in AGW. In addition, we used in vitro assays (ELISA, HPV-transfection models) to further investigate in vivo findings. IM treatment leads to a strong recruitment of neutrophils with thrombosis of small skin vessels within 8 h, in a sense of immunothrombosis. In vivo and in vitro analyses showed that IM supports a prothrombotic environment by endothelial cell activation and von Willebrand factor (VWF) secretion, in addition to induction of neutrophil extracellular traps (NETosis). IM superinduces CXCL8/IL-8 expression in HPV-E6/E7 transfected HaCaT cells when compared to non-infected keratinocytes. Rapid ablation of warts after IM treatment can be well explained by the observed immunothrombosis. This new mechanism has so far only been observed in HPV-induced lesions and is completely different from the mechanisms we see in the treatment of transformed keratinocytes in actinic keratosis. Our initial findings indicate an HPV-specific effect, which could be also of interest for the treatment of other HPV-induced lesions. Larger studies are now needed to further investigate the potential of IM in different HPV tumors.