Diagnostic delay, comorbid hidradenitis suppurativa and the prognostic value of bacterial culture in folliculitis decalvans: A cohort study.

BACKGROUND: Folliculitis decalvans (FD) is a type of primary neutrophilic cicatricial alopecia often leading to irreversible hair loss. Data on its epidemiology, clinical features, outcomes, and prognostic factors are limited. OBJECTIVE: To evaluate a cohort of patients with FD and identify characteristics of severe disease and prognostic factors which impede remission. PATIENTS AND METHODS: This retrospective cohort study included 192 patients diagnosed with FD and followed for at least six months at a tertiary center between 2010 and 2020. RESULTS: There was a diagnostic delay averaging 22.2 (± 29.7) months. Comorbid follicular occlusion disorders were common. Bacterial cultures were positive in 45.6% of the cases, with Staphylococcus (S.) aureus being the most common pathogen. Severe disease was associated with comorbid hidradenitis suppurativa and a positive bacterial culture, particularly S. aureus. 50.7% of patients experienced complete remission: 32% within the first six months of treatment and 18.7% later during follow-up. Relapses were frequent. Negative prognostic factors for achieving remission included younger age and a positive bacterial culture. CONCLUSIONS: There is a need for the education of dermatologists to reduce the diagnostic delay. Screening FD patients for comorbid hidradenitis suppurativa and obtaining bacterial cultures is important for treatment planning.

The need for fast and accurate detection of dermatomycosis.

Dermatomycosis of the hair, skin, or nails is one of the most common fungal infections worldwide. Beyond permanent damage to the affected area, the risk of severe dermatomycosis in immunocompromised people can be life-threatening. The potential risk of delayed or improper treatment highlights the need for a rapid and accurate diagnosis. However, with traditional methods of fungal diagnostics such as culture, a diagnosis can take several weeks. Alternative diagnostic technologies have been developed which allow for an appropriate and timely selection of an antifungal treatment, preventing nonspecific over-the-counter self-medication. Such techniques include molecular methods, such as polymerase chain reaction (PCR), real-time PCR, DNA microarray, next-generation sequencing, in addition to matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Molecular methods can help close the 'diagnostic gap' observed with traditional cultures and microscopy and allow for a rapid detection of dermatomycosis with increased sensitivity and specificity. In this review, advantages and disadvantages of traditional and molecular techniques are discussed, in addition to the importance of species-specific dermatophyte determination. Finally, we highlight the need for clinicians to adapt molecular techniques for the rapid and reliable detection of dermatomycosis infections and to reduce adverse events.

Dermatomycosis is one of the most common fungal infections worldwide. Traditional fungal diagnostics are limited and can take several weeks. Molecular techniques can detect dermatomycosis pathogens quickly and allow for species-specific identification which is important for treatment.

Identification and Characterization of Mesotrione-Resistant Grain Sorghum [Sorghum bicolor (L.) Moench]: A Viable Option for Postemergence Grass Weed Control.

Mesotrione is effective in controlling a wide spectrum of weeds in corn but not registered for postemergence use in sorghum because of crop injury. We screened a sorghum germplasm collection and identified two mesotrione-resistant sorghum genotypes (G-1 and G-10) and one susceptible genotype (S-1) in an in vitro plate assay. A mesotrione dose-response assay under greenhouse and field conditions confirmed that G-1 and G-10 are highly resistant compared to S-1. We found enhanced metabolism of mesotrione in G-1 and G-10 using HPLC assay, and a significant reduction in biomass accumulation was found in G-1 and G-10 plants pretreated with cytochrome P450 (CYP)-inhibitors malathion or piperonyl butoxide, indicating the involvement of CYPs in the metabolism of mesotrione. Genetic analyses using F1 and F2 progenies generated by crossing G-1 and G-10 separately with S-1 revealed that mesotrione resistance in sorghum is controlled by a single dominant gene along with several genes with minor effects.

A clinicopathological description of COVID-19-induced chilblains (COVID-toes) correlated with a published literature review.

BACKGROUND: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation. METHODS: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT-scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy. RESULTS: COVID-19-induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work-up in this study ruled-out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases. CONCLUSION: This study provides further clinicopathologic evidence of COVID-19-related chilblains. Negative PCR and antibody tests do not rule-out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis).

Assessment of a Diagnostic Classification System for Management of Lesions to Exclude Melanoma.

Importance: The proposed MOLEM (Management of Lesion to Exclude Melanoma) schema is more clinically relevant than Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MATH-Dx) for the management classification of melanocytic and nonmelanocytic lesions excised to exclude melanoma. A more standardized way of establishing diagnostic criteria will be crucial in the training of artificial intelligence (AI) algorithms. Objective: To examine pathologists' variability, reliability, and confidence in reporting melanocytic and nonmelanocytic lesions excised to exclude melanoma using the MOLEM schema in a population of higher-risk patients. Design, Setting, and Participants: This cohort study enrolled higher-risk patients referred to a primary care skin clinic in New South Wales, Australia, between April 2019 and December 2019. Baseline demographic characteristics including age, sex, and related clinical details (eg, history of melanoma) were collected. Patients with lesions suspicious for melanoma assessed by a primary care physician underwent clinical evaluation, dermoscopy imaging, and subsequent excision biopsy of the suspected lesion(s). A total of 217 lesions removed and prepared by conventional histologic method and stained with hematoxylin-eosin were reviewed by up to 9 independent pathologists for diagnosis using the MOLEM reporting schema. Pathologists evaluating for MOLEM schema were masked to the original histopathologic diagnosis. Main Outcomes and Measures: Characteristics of the lesions were described and the concordance of cases per MOLEM class was assessed. Interrater agreement and the agreement between pathologists' ratings and the majority MOLEM diagnosis were calculated by Gwet AC1 with quadratic weighting applied. The diagnostic confidence of pathologists was then assessed. Results: A total of 197 patients were included in the study (102 [51.8%] male; 95 [48.2%] female); mean (SD) age was 64.2 (15.8) years (range, 24-93 years). Overall, 217 index lesions were assessed with a total of 1516 histological diagnoses. Of 1516 diagnoses, 677 (44.7%) were classified as MOLEM class I; 120 (7.9%) as MOLEM class II; 564 (37.2%) as MOLEM class III; 114 (7.5%) as MOLEM class IV; and 55 (3.6%) as MOLEM class V. Concordance rates per MOLEM class were 88.6% (class I), 50.8% (class II), 76.2% (class III), 77.2% (class IV), and 74.2% (class V). The quadratic weighted interrater agreement was 91.3%, with a Gwet AC1 coefficient of 0.76 (95% CI, 0.72-0.81). The quadratic weighted agreement between pathologists' ratings and majority MOLEM was 94.7%, with a Gwet AC1 coefficient of 0.86 (95% CI, 0.84-0.88). The confidence in diagnosis data showed a relatively high level of confidence (between 1.0 and 1.5) when diagnosing classes I (mean [SD], 1.3 [0.3]), IV (1.3 [0.3]) and V (1.1 [0.1]); while classes II (1.8 [0.2]) and III (1.5 [0.4]) were diagnosed with a lower level of pathologist confidence (≥1.5). The quadratic weighted interrater confidence rating agreement was 95.2%, with a Gwet AC1 coefficient of 0.92 (95% CI, 0.90-0.94) for the 1314 confidence ratings collected. The confidence agreement for each MOLEM class was 95.0% (class I), 93.5% (class II), 95.3% (class III), 96.5% (class IV), and 97.5% (class V). Conclusions and Relevance: The proposed MOLEM schema better reflects clinical practice than the MPATH-Dx schema in lesions excised to exclude melanoma by combining diagnoses with similar prognostic outcomes for melanocytic and nonmelanocytic lesions into standardized classification categories. Pathologists' level of confidence appeared to follow the MOLEM schema diagnostic concordance trend, ie, atypical naevi and melanoma in situ diagnoses were the least agreed upon and the most challenging for pathologists to confidently diagnose.

Cutaneous lymphocytic thrombophilic (macular) arteritis.

Macular arteritis (MA) has a striking discordance between the clinical presentation of hyperpigmented macules and the histopathologic findings of a lymphocytic arteritis with intraluminal hyalinized fibrin ring and thrombosis. It has been proposed that MA represents the chronic, indolent, lymphocytic form of the neutrophil-predominant cutaneous polyarteritis nodosa. MA usually affects middle-aged women asymptomatically on the legs. There is also a slightly more severe variant with more infiltrated plaques and livedo racemosa, termed lymphocytic thrombophilic arteritis. MA and lymphocytic thrombophilic arteritis have similar histologic features, both with a largely intact vascular elastic lamina, despite the abundant fibrin and endarteritis obliterans. There is no evidence for progression from MA to lymphocytic thrombophilic arteritis to cutaneous polyarteritis nodosa, and aggressive therapy should be avoided in MA, given the indolent, benign disease course.

Histologic Patterns and Clues to Autoinflammatory Diseases in Children: What a Cutaneous Biopsy Can Tell Us.

Autoinflammation is defined by aberrant, antigen-independent activation of the innate immune signaling pathways. This leads to increased, pro-inflammatory cytokine expression and subsequent inflammation. In contrast, autoimmune and allergic diseases are antigen-directed immune responses from activation of the adaptive immune system. The innate and adaptive immune signaling pathways are closely interconnected. The group of 'complex multigenic diseases' are a result of mutual dysregulation of both the autoinflammatory and autoimmune physiologic components. In contrast, monogenic autoinflammatory syndromes (MAIS) result from single mutations and are exclusively autoinflammatory in their pathogenesis. Studying the clinical and histopathological findings for the various MAIS explains the phenotypical correlates of their specific mutations. This review aims to group the histopathologic clues for autoinflammation into three recognizable patterns. The presence of these histologic patterns in a pediatric patient with recurrent fevers and systemic inflammation should raise suspicion of an autoinflammatory component in MAIS, or, more frequently, in a complex multigenic disease. The three major histopathological patterns seen in autoinflammation are as follows: (i) the 'neutrophilic' pattern, seen in urticarial neutrophilic dermatosis, pustular psoriasis, aseptic neutrophilic folliculitis, and Sweet's syndrome; (ii) the 'vasculitic' pattern seen in small vessel-vasculitis (including hypersensitivity/leukocytoclastic vasculitis, thrombosing microangiopathy and lymphocytic vasculitis), and intermediate-sized vessel vasculitis, mimicking polyarteritis nodosa; and (iii) the 'granulomatous' pattern. Beyond these three patterns, there are additional histopathologic clues, which are detailed below. It is important for a dermatopathologist to recognize the patterns of autoinflammation, so that a diagnosis of MAIS or complex multigenic diseases may be obtained. Finally, careful histopathologic analyses could contribute to a better understanding of the various clinical manifestations of autoinflammation.

Variability in the Histopathological Diagnosis of Non-Melanocytic Lesions Excised to Exclude Melanoma.

INTRODUCTION: The differential diagnosis of lesions excised to exclude melanoma include a variety of benign and malignant melanocytic and non-melanocytic lesions. OBJECTIVES: We examined the variability between pathologists in diagnosing non-melanocytic lesions. METHODS: As part of a larger study prospectively examining the diagnosis of lesions excised to exclude melanoma in 198 patients at a primary care skin cancer clinic in Newcastle, Australia, we compared diagnosis made by 5 experienced dermatopathologists, of 44 non-melanocytic lesions in 44 patients aged 22-90. RESULTS: Forty-four lesions (out of 217 in total) were non-melanocytic. Among the 5 pathologists who examined each case there was marked variability in the terminology used to diagnose each case. The most common variability was found between seborrheic keratosis, large cell acanthoma, solar lentigo, and lichenoid keratosis. The diagnosis made by the majority of the pathologists was deemed to be the reference diagnosis. Versus majority diagnosis, 4% of benign lesions were considered malignant, and 7% of malignant diagnoses were considered as benign. CONCLUSIONS: The different terminology adopted and lack of consensus in the diagnosis of these non-melanocytic lesions in this setting suggests that training AI systems using gold standards may be problematic. We propose a new management classification scheme called MOLEM (Management of Lesions Excised to exclude Melanoma) which expands the previously described MPATH-dx to include non-melanocytic lesions.

Recombinant human hyaluronidase PH20-mediated dermal spreading activity in mice is not altered by steroids, antihistamines, or salicylic acid.

OBJECTIVES: Drug-drug interaction studies for hyaluronidase safety assessments have evaluated only animal-derived enzyme preparations. We therefore set out to evaluate whether high-dose administration of two antihistamines, a potent corticosteroid, steroid hormone, adrenocorticotropic hormone (ACTH), or salicylic acid would alter the dispersive activity of recombinant human hyaluronidase PH20 (rHuPH20). METHODS: NCr nu/nu mice were pretreated with diphenhydramine, cetirizine, dexamethasone, estrogen, ACTH, salicylic acid, and/or neutral-buffered saline (NBS). An hour following final pretreatment, dosed mice were anesthetized with ketamine/xylazine and placed in an imaging chamber. A 120 mg/mL immunoglobulin G (IgG) solution with 0.3 µg/mL IgGDL755 (labeled IgG) was injected intradermally, with/without 2,000 U/mL rHuPH20. Fluorescent images of labeled IgG dispersion were acquired ≤20 min post injection. RESULTS: Dispersion of high-concentration labeled IgG combined with rHuPH20 was greater at all time points vs. antibody alone. At 20 min post injection (last time point), the antibody dispersion area was significantly increased with rHuPH20 vs. without rHuPH20 (p≤0.005). The relative percent increase in antibody dispersion with rHuPH20 ranged from 22.8‒106.6% over the 20-min time course, compared with the corresponding non-rHuPH20 treated groups. The area of labeled IgG dispersion was statistically similar between rHuPH20 groups pretreated with an active compound and their paired NBS pretreated controls. CONCLUSIONS: The addition of 2,000 U/mL rHuPH20 to a high-concentration antibody solution reproducibly incre-ased local antibody dispersion. Systemic pretreatment with diphenhydramine, cetirizine, dexamethasone, estrogen, ACTH, or salicylic acid did not affect the enzymatic spreading activity of rHuPH20, as measured by intradermal dispersion of labeled IgG in mice.

Clinicopathologic and immunophenotypic characterization of lichen planopilaris and central centrifugal cicatricial alopecia: A comparative study of 51 cases.

BACKGROUND: The purpose of the study was to compare the histopathologic and immunophenotypic features of central centrifugal cicatricial alopecia (CCCA) and lichen planopilaris (LPP) to better characterize and differentiate these two clinical entities. CCCA remains an ill-defined and still-unsettled histologic entity and many hair loss experts regard CCCA to be histologically indistinguishable from LPP. Given the overlapping histologic features of these two lymphocyte-predominant cicatricial alopecias, and the lack of consensus regarding the significance of proposed distinctions, dermatopathologists face difficulty in providing clinicians and patients certainty with a definitive diagnosis of CCCA vs LPP. METHODS: We performed a retrospective review of 51 scalp biopsies of patients with either the clinical diagnosis of CCCA (27 cases) or LPP (24 cases). Clinical information, histologic features of hematoxylin-eosin-stained sections, and a panel of immunohistochemical markers were evaluated on scalp biopsies. Tested parameters were quantified, and statistical analysis was performed. RESULTS: Our study found no differences on either histologic assessment or immunophenotypic characterization between cases of classic LPP and CCCA. CONCLUSION: The conclusion of this study is that the inflammatory infiltrates in CCCA and LPP are not only histologically similar but also immunophenotypically indistinguishable.