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.

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.

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).

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.

Immunohistochemical characterization of benign activation of junctional melanocytes and melanoma in situ of the nail unit.

BACKGROUND: Immunohistochemical (IHC) stains that distinguish benign, pigmented nail lesions from malignancy are needed. Candidate markers of malignant transformation include p16, HMB45, and Ki-67, with p16 being of particular interest. There is limited knowledge about the spectrum of p16 expression in pigmented lesions, especially junctional melanocytic proliferations of the nail. The objective of this study was to determine if any of these markers demonstrate diagnostic utility in distinguishing between benign activation of junctional melanocytes (BAM) and melanoma in situ (MIS) of the nail unit. METHODS: In this retrospective study, ten cases of BAM and eight cases of MIS were identified. Archival slides available for review included H&E (hematoxylin and eosin), Fontana-Masson, and MelanA (Mart1) IHC slides. IHC studies for p16, HMB45, and dual-color Ki-67/MelanA (Mart1) were then performed. RESULTS: None of the tested IHC stains distinguished BAM from MIS. p16 IHC expression was uniformly negative with the exception of two cases of MIS. HMB45 was positive in all BAM and MIS cases. Ki-67/MelanA showed positive Ki-67 staining of MelanA-positive melanocytes in two cases of MIS, and all other cases of MIS and BAM were negative for Ki-67. The two positive p16 and two positive Ki-67/MelanA cases were non-overlapping. CONCLUSION: p16, HMB45, and Ki-67/MelanA IHC studies show no apparent utility in distinguishing BAM from MIS in the nail unit.

Longitudinal Melanonychia Biopsy: What Not to Do.

The nail matrix biopsy is an important technique in confirming or excluding a diagnosis of melanoma in a patient with longitudinal melanonychia. Dermatologists are the first-line diagnosticians for these pigmented lesions of the nail unit, however, for different reasons, some are reluctant to perform a nail biopsy. This case demonstrates how a poor biopsy technique resulted in a misdiagnosis in a patient with melanoma in situ. J Drugs Dermatol. 2018;17(5):587-588.

A case illustrating successful eradication of recurrent, aggressive basal cell carcinoma located in a scar with vismodegib.

Vismodegib is a small molecule inhibitor of the Hedgehog signaling pathway that has shown efficacy in the control of locally advanced or metastatic basal cell carcinoma, although proof of its effectiveness in the elimination of aggressive tumors is lacking. We report a case and provide complete histological evidence of a 69-year-old gentleman who presented with a recurrent, infiltrative, and sclerosing (morpheiform) basal cell carcinoma on his left upper lip that was entirely eradicated with a three-month course of vismodegib 150 mg daily. Complete histologic clearance of a tumor in a recurrent, infiltrative, and sclerosing basal cell carcinoma with vismodegib is uncommon.

Micropost arrays for measuring stem cell-derived cardiomyocyte contractility.

Stem cell-derived cardiomyocytes have the potential to be used to study heart disease and maturation, screen drug treatments, and restore heart function. Here, we discuss the procedures involved in using micropost arrays to measure the contractile forces generated by stem cell-derived cardiomyocytes. Cardiomyocyte contractility is needed for the heart to pump blood, so measuring the contractile forces of cardiomyocytes is a straightforward way to assess their function. Microfabrication and soft lithography techniques are utilized to create identical arrays of flexible, silicone microposts from a common master. Micropost arrays are functionalized with extracellular matrix protein to allow cardiomyocytes to adhere to the tips of the microposts. Live imaging is used to capture videos of the deflection of microposts caused by the contraction of the cardiomyocytes. Image analysis code provides an accurate means to quantify these deflections. The contractile forces produced by a beating cardiomyocyte are calculated by modeling the microposts as cantilever beams. We have used this assay to assess techniques for improving the maturation and contractile function of stem cell-derived cardiomyocytes.

Primary scalp alopecia: new histopathological tools, new concepts and a practical guide to diagnosis.

The diagnosis of primary scalp alopecia remains one of the most challenging fields in dermatopathology. In this review, we would like to connect the established classification of primary alopecia into scarring (cicatricial) and non-scarring (non-cicatricial) with current concepts. We introduce a simplified pathway for the diagnosis of the most common causes of alopecia, including a discussion of tissue processing techniques and use of immunohistochemistry.

Interstitial Pressure in Pancreatic Ductal Adenocarcinoma Is Dominated by a Gel-Fluid Phase.

Elevated interstitial fluid pressure can present a substantial barrier to drug delivery in solid tumors. This is particularly true of pancreatic ductal adenocarcinoma, a highly lethal disease characterized by a robust fibroinflammatory response, widespread vascular collapse, and hypoperfusion that together serve as primary mechanisms of treatment resistance. Free-fluid pressures, however, are relatively low in pancreatic ductal adenocarcinoma and cannot account for the vascular collapse. Indeed, we have shown that the overexpression and deposition in the interstitium of high-molecular-weight hyaluronan (HA) is principally responsible for generating pressures that can reach 100 mmHg through the creation of a large gel-fluid phase. By interrogating a variety of tissues, tumor types, and experimental model systems, we show that an HA-dependent fluid phase contributes substantially to pressures in many solid tumors and has been largely unappreciated heretofore. We investigated the relative contributions of both freely mobile fluid and gel fluid to interstitial fluid pressure by performing simultaneous, real-time fluid-pressure measurements with both the classical wick-in-needle method (to estimate free-fluid pressure) and a piezoelectric pressure catheter transducer (which is capable of capturing pressures associated with either phase). We demonstrate further that systemic treatment with pegylated recombinant hyaluronidase (PEGPH20) depletes interstitial HA and eliminates the gel-fluid phase. This significantly reduces interstitial pressures and leaves primarily free fluid behind, relieving the barrier to drug delivery. These findings argue that quantifying the contributions of free- and gel-fluid phases to hydraulically transmitted pressures in a given cancer will be essential to designing the most appropriate and effective strategies to overcome this important and frequently underestimated resistance mechanism.

Distinguishing diffuse alopecia areata (AA) from pattern hair loss (PHL) using CD3(+) T cells.

BACKGROUND: Distinguishing between diffuse subacute alopecia areata (AA), in which the peribulbar infiltrate is absent, and pattern hair loss is challenging, particularly in cases that lack marked follicular miniaturization and a marked catagen/telogen shift. OBJECTIVE: We sought to distinguish diffuse AA from pattern hair loss using CD3(+) T lymphocytes. METHODS: A total of 28 cases of subacute AA and 31 cases of pattern hair loss were selected and a 4-mm punch biopsy was performed. All the specimens were processed using the "HoVert" (horizontal and vertical) technique. In all cases, hematoxylin-eosin and immunohistochemical stains for CD3, CD4, CD8, and CD20 were performed. RESULTS: The presence of CD3(+) lymphocytes within empty follicular fibrous tracts (stela), even without a concomitant peribulbar infiltrate, is a reliable histopathological clue in supporting a diagnosis of AA (sensitivity 0.964, specificity 1, P ≤ .001). LIMITATIONS: Limited tissue for analysis remained in the clinical sample tissue blocks. CONCLUSION: The presence of CD3(+) T-cells within empty follicular fibrous tracts (stela) supports a diagnosis of AA.

Recombinant human hyaluronidase PH20 does not stimulate an acute inflammatory response and inhibits lipopolysaccharide-induced neutrophil recruitment in the air pouch model of inflammation.

Hyaluronidase (Hyal) and low m.w. hyaluronan (LMW HA) fragments have been widely reported to stimulate the innate immune response. However, most hyaluronidases used were purified from animal tissues (e.g., bovine testis Hyal [BTH]), and contain endotoxin and other unrelated proteins. We tested a highly purified recombinant human Hyal (rHuPH20) and endotoxin-free HA fragments from M(r) 5,000 to 1,500,000 in the rodent air pouch model of inflammation to determine their potential for stimulation of the innate immune response. Exogenous LMW HA fragments (average M(r) 200,000) failed to induce either cytokine/chemokine production or neutrophil infiltration into the air pouch. Challenging the air pouch with LPS or BTH stimulated production of cytokines and chemokines but rHuPH20 did not, suggesting that neither PH20 nor generation of LMW HA fragments in situ stimulates cytokine and chemokine production. LPS and BTH also induced neutrophil infiltration into the air pouch, which was not observed with rHuPH20 treatment. Endotoxin-depleted BTH had much reduced proinflammatory activity, suggesting that the difference in inflammatory responses between rHuPH20 and BTH is likely due to endotoxin contaminants in BTH. When rHuPH20 was dosed with LPS, the induction of cytokines and chemokines was the same as LPS alone, but neutrophil infiltration was inhibited, likely by interrupting HA-CD44 interaction. Our results indicate that neither rHuPH20 nor its directly generated HA catabolites have inflammatory properties in the air pouch model, and rHuPH20 can instead inhibit some aspects of inflammation, such as neutrophil infiltration into the air pouch.

Pseudoangiomatous xanthelasmoid mastocytosis: two case reports showing the hypervascularity of this rare variant of cutaneous mastocytosis.

Xanthelasmoid mastocytosis or xanthelasmoidea is a rare clinical variant of cutaneous mastocytosis characterized by a yellow hue of the clinical lesions, which are often misdiagnosed as juvenile xanthogranuloma. We present two pediatric cases of xanthelasmoid mastocytosis presenting as isolated mastocytomas, which are notable histopathologically for their hypervascularity. This pseudoangiomatous variant of cutaneous mastocytosis is important for pathologists to have knowledge of, so that a diagnosis of a vascular tumor is not rendered accidentally. The yellow hue has previously been explained by the usual deep and solid dermal mast cell infiltrate. In the two presented cases, however, the mast cell infiltrate was sparse, and the yellow color cannot be related to infiltrate density. We believe that the hypervascularity is at least one factor in the production of clinical xanthelasmoid appearance, and we propose the term 'pseudoangiomatous xanthelasmoid mastocytosis' to properly describe this rare variant of cutaneous mastocytosis.

Macular arteritis associated with concurrent HIV and hepatitis B infections: a case report and evidence for a disease spectrum association with cutaneous polyarteritis nodosa.

We report the first case of macular arteritis in a 33-year-old Black, African female with concurrent human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Of particular interest in macular arteritis is the striking discordance between the clinical presentation and the histopathological findings, a fact that both dermatologists and dermatopathologists should be aware. Histopathologically, the case showed typical findings of macular arteritis with a perivascular, predominantly lymphocytic, infiltrate and intraluminal thrombosis. Both HIV and HBV have been reported as viral inducers of cutaneous polyarteritis nodosa (PAN). Their association with macular arteritis in this case supports existing evidence that macular arteritis and cutaneous PAN represent a single-disease spectrum of vasculitides, with macular arteritis representing the chronic, lymphocytic and indolent stage, and cutaneous PAN the neutrophilic, acute stage with a risk for systemic progression. Lymphocytic thrombophilic arteritis (LTA), a third, uncommon disease would be in between macular arteritis and cutaneous PAN on a spectrum. Features of this case and other published cases provide strong evidence that there is a single, mild-to-severe disease spectrum of macular arteritis-LTA-cutaneous PAN.

Coral contact dermatitis.

Corals can elicit both toxic and allergic reactions upon contact with the skin. Clinical presentations vary depending on whether the reaction is acute, delayed, or chronic. Literature concerning cutaneous reactions to corals and other Cnidarians is scarce. Herein we report a case of delayed contact hypersensitivity reaction to coral and review the clinical and histopathological features of coral contact dermatitis.

Absence of catagen/telogen phase and loss of cytokeratin 15 expression in hair follicles in lichen planopilaris.

BACKGROUND: Lichen planopilaris (LPP) is a lymphocyte-mediated cicatricial alopecia mostly involving the bulge region of the hair follicle. The origin of LPP is unknown. Therapy for LPP often does not prevent disease progression. We describe histologic and immunohistologic features that aid in diagnosis and provide an explanation for disease progression in LPP. OBJECTIVE: We sought to demonstrate a decrease in the number of catagen-/telogen-phase follicles and to confirm the loss of cytokeratin 15 (CK15) expression in the stem cells of LPP-affected follicles. METHODS: In all, 144 LPP cases were retrieved; 55 cases were stained immunohistochemically, targeting the CK15 antigen with 40 cases ultimately analyzed for CK15 expression. RESULTS: Catagen/telogen phase was significantly decreased or absent in all cases of LPP, a novel clue useful in histologic diagnostics. The loss of CK15+ stem cells in most affected follicles in LPP was also confirmed, with unaffected follicles retaining CK15+ stem cells. LIMITATIONS: Limited tissue for analysis remained in the clinical sample tissue blocks. CONCLUSION: Damaged follicles that have lost their CK15+ stem cells disappear when they enter catagen phase. CK15+ stem cell loss explains the clinical observation that LPP progresses despite immunosuppressive therapies. Finally, the absence of catagen/telogen hair follicles is a helpful diagnostic clue for LPP.