A Series of 69 COVID-related Dermatoses With Biopsy, Immunohistochemistry With Anti-spike 3, in situ Hybridization and PCR: A Critical Reappraisal of Viral Involvement in COVID-19 Skin Lesions.

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.

A Series of 69 COVID-related Dermatoses With Biopsy, Immunohistochemistry With Anti-spike 3, in situ Hybridization and PCR: A Critical Reappraisal of Viral Involvement in COVID-19 Skin Lesions. / [Articulo traducido] Serie de 69 dermatosis relacionadas con la COVID-19 con biopsia, estudio inmunohistoquímico con anti-spike 3, hibridación in situ y PCR: Una revisión crítica de la afectación cutánea relacionada con la COVID-19.

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.

No evidence of Borrelia in cutaneous infiltrates of B-cell lymphomas with a highly sensitive, semi-nested real-time polymerase chain reaction targeting the 5S-23S intergenic spacer region.

BACKGROUND: The role of Borrelia in the development of skin lymphomas has been under discussion for decades. A similar association has been shown for Helicobacter pylori and gastric lymphomas (MALT type). Nevertheless, few molecular studies investigated Borrelia in skin lymphomas and the results are controversial. METHODS: We analysed 46 formalin-fixed, paraffin-embedded skin specimens of clincopathologically confirmed B-cell lymphomas (15 marginal zone lymphomas; 20 follicular lymphomas; three diffuse large B-cell lymphomas; eight secondary cutaneous infiltrates) taken from 36 patients from Northern Germany, an endemic area for Borrelia. Fifteen pseudolymphomatous lesions of cutaneous Borreliosis served as the control. Both groups were examined with a real-time (rt) PCR and a semi-nested PCR targeting the 5S-23S intergenic spacer region (IGS). A multiplex PCR was used to investigate B-cell clonality in all lymphomatous infiltrates (Biomed Primers). RESULTS: With both assays no Borrelia burgdorferi-specific DNA was identified in any of the B-cell lymphomas, while all 15 Borreliosis specimens gave a positive PCR result in the semi-nested PCR protocol, 12 were also positive in the rt PCR (P < 0.01). All B-cell lymphomas showed monoclonal IgH-Rearrangement. Analysis of cutaneous B-cell lymphomas from available studies including ours (n = 334) reveals an odds ratio <1. CONCLUSION: While some previous studies suggested an association between B. burgdorferi and the development of cutaneous B-cell lymphomas in endemic areas, we were unable to confirm this in our patients, despite a highly sensitive Borrelia PCR assay. Our results including meta-analysis of previous studies question the need for antibiotic therapy in patients with cutaneous B-cell lymphomas.

Quality of life and clinical characteristics of self-improving congenital ichthyosis within the disease spectrum of autosomal-recessive congenital ichthyosis.

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.

[Rheumatoid arthritis : These dermatoses lead you to the diagnosis]. / Rheumatoide Arthritis : Bei welchen Hautveränderungen sollte man daran denken?

BACKGROUND: Rheumatoid arthritis is one of the most common autoimmune disorders. In addition to chronic arthritis, rheumatoid arthritis may present a variety of extra-articular manifestations, most commonly of the skin. OBJECTIVES: Cutaneous manifestations associated with rheumatoid arthritis can be diverse, both specific and nonspecific. Which dermatoses should lead you to the diagnosis of an underlying rheumatoid arthritis? METHODS: Evaluation of exemplary overviews, case presentations and relevant textbook articles. RESULTS: Rheumatoid arthritis presents various specific and nonspecific skin manifestations. Besides visual diagnosis like classic rheumatoid nodules a histopathologic correlation or an interdisciplinary approach is often needed, such as for diagnosis of pyoderma gangrenosum. CONCLUSIONS: The early detection and correct classification of cutaneous manifestations associated with rheumatoid arthritis can be groundbreaking for a successful therapy and a consequently better prognosis for patients with rheumatoid arthritis. Therefore dermatologists bear responsibility in the patient-centered care.

Refining the dermatological spectrum in primary immunodeficiency: mucosa-associated lymphoid tissue lymphoma translocation protein 1 deficiency mimicking Netherton/Omenn syndromes.

The proteinase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), which forms part of the caspase recruitment domain-containing protein 11-B-cell lymphoma 10-MALT1 signalosome complex, plays a direct role in nuclear factor kappa B activation. Here, we describe the case of a female infant with severe immune dysregulation leading to recurrent systemic infections, failure to thrive and severe crises of ichthyosiform erythroderma with high levels of serum IgE. Hence, initial symptoms indicated Netherton syndrome or Omenn syndrome. Surprisingly, sequence analyses of SPINK5 and RAG1/RAG2, respectively, excluded these diseases. During the hospital stay the patient's health deteriorated, despite intensive care therapy, and she died. In order to delineate the diagnosis, whole-exome sequencing was performed. Two compound heterozygous mutations in MALT1 were found and verified by Sanger sequencing (exon 2 c.245T>C, exon 2 c.310dup), which led to a MALT1 deficiency at the protein level. Based on these results, an immunological analysis was performed, as was immunofluorescence staining of key skin proteins, to confirm a diagnosis of MALT1 deficiency. This case report provides a closer description of the clinical and histological skin phenotype of MALT1 deficiency, and we conclude that MALT1 deficiency must be considered a possible differential diagnosis of Netherton and Omenn syndromes. What's already known about this topic? Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) deficiency is a combined immunodeficiency. MALT1 is part of the caspase recruitment domain-containing protein 11-B-cell lymphoma 10-MALT1 signalosome complex, which is essential for nuclear factor kappa B activation. Current publications describe a phenotype of recurrent systemic infections; only in a few cases has an inflammatory involvement of the integument been described. What does this study add? A closer description of the cutaneous phenotype of MALT1 deficiency in a patient with two novel MALT1 mutations. Immune mapping of follicular epidermis shows lympho-epithelial Kazal-type-related inhibitor is reduced in MALT1 deficiency and absent on interfollicular staining. Clinically, MALT1 deficiency mimics Netherton syndrome and Omenn syndrome, and should be considered a differential diagnosis.

Neurokinin 1 receptor antagonists exhibit peripheral effects in prurigo nodularis including reduced ERK1/2 activation.

BACKGROUND: Aprepitant is a neurokinin 1 receptor (NK1R) antagonist used for its antipruritic properties in dermatoses and systemic diseases. The mode of action is still unclear. A peripheral effect is assumed as aprepitant shows efficacy in inflammatory skin diseases including prurigo nodularis (PN). OBJECTIVES: To investigate the peripheral effects of NK1R antagonism in PN and cell culture models. METHODS: Subjects with PN received an aprepitant treatment. Clinical, morphological and immunohistochemical changes were investigated in skin biopsies before and after treatment. Expression of NK1R was analysed by immunohistochemistry and for downstream pathways ((p)ERK1/2) by Western blotting in PN patients and matched healthy volunteers. Effects of NK1R blocking were analysed in cell cultures of primary keratinocytes by Western blotting for (p)ERK1/2 and by qPCR for NK1R, interleukin (IL)-1beta, IL-6, IL-8 and TNFalpha. RESULTS: Aprepitant treatment showed significant reduction in pruritus intensity (P < 0.05) in PN and relevant immunohistochemical changes (down: CD5, CD25, up: CD79a, IL4). NK1R expression was higher in keratinocytes of PN patients compared to healthy controls. After treatment, epidermal NK1R expression increased while expression and activation of ERK1/2 decreased. In vitro, receptor up-regulation and reduced expression and activation of ERK1/2 were confirmed and reduced IL-expression shown when blocking NK1R. CONCLUSION: Our data confirm that NK1R antagonists such as aprepitant exhibit effects in the skin. Epidermal receptor expression, epidermal inflammatory ILs, ERK1/2 MAPK signalling and cutaneous inflammatory infiltrate were targets of NK1R antagonism. This may explain partly the antipruritic effect of NK1R antagonists next to its role in the central nervous system.

Prurigo Activity Score (PAS): validity and reliability of a new instrument to monitor chronic prurigo.

BACKGROUND: Currently available tools to monitor patients with chronic prurigo over time focus on pruritus and quality of life parameters, while no instrument objectively assessing the pruriginous lesions is yet available. OBJECTIVE: The objective of this study was to develop a physician-assessed Prurigo Activity Score (PAS), a new tool to monitor the distribution and activity of chronic prurigo lesions and to evaluate its reliability and validity. METHODS: The 7-item PAS questionnaire as well as validated pruritus intensity scales (VAS, NRS) and a skin-related quality of life score (DLQI) were completed for 264 patients (172 females, age 61 years) at least twice over a period of 2 years. In addition, a 60-min test-retest reliability test was performed by four experts for a random sample of 12 patients. RESULTS: The PAS showed good test-retest reliability (Cohens κ > 0.61; Cronbach-alpha > 0.76), ordinal or metric items showed high inter-rater reliability (Kendalls > 0.61) and items recording the number of lesions correlated significantly to each other (P < 0.001). The highest correlation to external constructs was achieved with DLQI. The feasibility test conducted by four raters indicated the suitability of PAS for tracking chronic prurigo in the clinical setting. DISCUSSION: The PAS is a useful tool to objectively monitor pruriginous lesions in chronic prurigo patients over time. The sensitivity of change in the PAS score should be analysed in future studies.

Dermatomyositis panniculitis: a clinicopathological and immunohistochemical study of 18 cases.

BACKGROUND: Panniculitis occurring in dermatomyositis is uncommon, with only a few cases described in the literature, most of them as case reports. OBJECTIVE: This report describes the clinicopathological and immunohistochemical findings in a series of 18 patients with panniculitis associated with dermatomyositis. METHODS: In each patient, we collected the clinical data of the cutaneous lesions as well as the characteristic clinical and laboratory findings. A series of histopathologic findings was recorded in the biopsy of each patient. A panel of antibodies was used in some cases to investigate the immunophenotype of the infiltrate. Data of treatment and follow-up were also collected. RESULTS: Of the 18 patients, 13 were female and 5 were male, ranging in age from 13 to 74 years (median, 46.4 years). In addition to panniculitis, all patients presented pathognomonic cutaneous findings of DM and reported proximal muscle weakness prior to the diagnosis of panniculitis. Muscle biopsy was performed in 17 patients and MRI in one, all with the diagnosis of inflammatory myopathy. None of the patients presented any associated neoplasia. Panniculitis lesions were located in the upper or lower limbs. Histopathology showed a mostly lobular panniculitis with lymphocytes as the main component of the infiltrate. Most cases showed also numerous plasma cells and lymphocytes surrounding necrotic adipocytes (rimming) were frequently seen. Lymphocytic vasculitis and abundant mucin interstitially deposited between collagen bundles of the dermis were also frequent findings. Late-stage lesions showed hyaline necrosis of the fat lobule and calcification. Immunohistochemistry demonstrated that most lymphocytes of the infiltrate were T-helper lymphocytes, with some B lymphocytes in the lymphoid aggregates and small clusters of CD-123-positive plasmacytoid dendritic cells in the involved fat lobule. CONCLUSION: Panniculitis in dermatomyositis is rare. Histopathologic findings of panniculitis dermatomyositis are identical to those of lupus panniculitis. Therefore, the final diagnosis requires clinic-pathologic correlation.

[Systematic analysis of pathological changes in inflammatory dermatoses : New dermatopathological criteria and algorithms]. / Systematische Analyse pathologischer Veränderungen bei entzündlichen Dermatosen : Neue dermatopathologische Kriterien und Algorithmen.

Standardized analysis of histological findings in a routinely stained section without knowledge of the clinical picture ("blind fashion") allows an objective assessment of the pathological changes. In inflammatory dermatoses diagnostic algorithms and criteria have been proven. They follow defined main inflammatory patterns, the composition of the inflammatory infiltrate and additional criteria. Taking into account the stage of development and the possibility of collision phenomena, this approach will give a histological diagnosis, or at least a limited number of differential diagnoses. However, the final diagnosis always results from the synopsis of the clinical picture and additional parameters. The modern development of algorithms and new histological criteria are outlined in autoimmune dermatoses, autoinflammatory syndromes, drug reactions and genodermatoses.

Successful monotherapy of pemphigus vegetans with minocycline and nicotinamide.

BACKGROUND: Pemphigus vegetans is a rare variant of pemphigus vulgaris, accounting for 1-2% of all pemphigus diseases. Systemic corticosteroids are the therapy of first choice in combination with immunosuppressants as steroid-sparing agents. OBJECTIVE: To highlight the exceptional but successful use of minocycline/nicotinamide monotherapy in pemphigus vegetans. METHODS: A review of the literature to date about pemphigus vegetans with special emphasis on therapy was performed. Due to its rarity, multiple anecdotal reports without long-term follow-up are available and prospective controlled trials are lacking. Only one retrospective study from Tunisia includes 17 patients with pemphigus vegetans. RESULTS: We present a 76-year-old woman with pemphigus vegetans achieving complete response to a minocycline/nicotinamide monotherapy at onset and at relapse of the disease. Treatment has been discontinued after repeated direct immunofluorescence (DIF) of previously affected normal skin and anti-desmoglein 3 antibodies had become negative. In addition, DIF of previously involved oral mucosa was negative. During long-term follow-up clinical remission has been maintained for more than 5 years. Up to now, negative results of serial performed indirect immunofluorescence and desmoglein ELISA testing also predict immunological remission. CONCLUSION: In our patient and in a case with oesophageal involvement, published more than 20 years ago, clearly the benefit of minocycline/nicotinamide monotherapy was demonstrated. We propose to consider minocycline/nicotinamide as first-line monotherapy in pemphigus vegetans, especially in elderly patients with comorbidities and contraindications to standard therapy, as it avoids the toxicities of systemic corticosteroids and immunosuppressants.

Species identification of dermatophytes in paraffin-embedded biopsies with a new polymerase chain reaction assay targeting the internal transcribed spacer 2 region and comparison with histopathological features.

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.

Fast, sensitive and specific diagnosis of infections with Leishmania spp. in formalin-fixed, paraffin-embedded skin biopsies by cytochrome b polymerase chain reaction.

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.

Scleredema. A multicentre study of characteristics, comorbidities, course and therapy in 44 patients.

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.

Genotyping of Borrelia from formalin-fixed paraffin-embedded skin biopsies of cutaneous borreliosis and tick bite reactions by assays targeting the intergenic spacer region, ospA and ospC genes.

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.