Underwent Skin Biopsy Research Articles

Application of Phosphorylated Alpha Synuclein (p-syn) Skin Biopsy in Clinical Practice: Audit at an Academic Medical Center (P8-9.004)

<h3>Objective:</h3> To assess how p-syn skin biopsy is being applied clinically by auditing its use in an academic medical center. <h3>Background:</h3> Cutaneous deposition of p-syn is found in synucleinopathies including Parkinson’s disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), and pure autonomic failure (PAF). Skin biopsy assessing for the presence of p-syn is an emerging diagnostic tool with reported good sensitivity and high specificity for detecting synucleinopathies. Commercial cutaneous testing for p-syn is now available in the US, though not yet in widespread clinical use despite its minimally invasive nature and relative accessibility in comparison to other testings such as DaTscan and MIBG myocardial scintigraphy. <h3>Design/Methods:</h3> All patients followed at our center who had undergone p-syn skin biopsy since its commercial availability were identified and their electronic medical records reviewed. <h3>Results:</h3> 10 patients underwent skin biopsies for p-sync from June 2021 to August 2022. 7 had isolated autonomic dysfunction; 2 had parkinsonism but potential alternative explanations (i.e. hydrocephalus, antidopaminergic medications), and 1 had speech apraxia with a question of Alzheimer or DLB. 5 of 7 patients with autonomic dysfunction had positive biopsies, obviating the search for other etiologies such as autoimmune disease or amyloidosis. The other 3 patients were also found to be p-sync positive. Affirming this diagnosis positively impacted subsequent monitoring and management and enabled accurate prognostication. <h3>Conclusions:</h3> Skin biopsy is a useful tool for diagnosing synucleinopathy in patients presenting with autonomic dysfunction. It can also add diagnostic value in patients with parkinsonism and other potential competing explanations. <b>Disclosure:</b> Dr. Wang has nothing to disclose. Dr. Robbins has received personal compensation in the range of $0-$499 for serving as a Consultant for Guidepoint Global Inc. The institution of Dr. Robbins has received research support from Diamond Endowment Fund. The institution of Dr. Robbins has received research support from Reeves Endowment Fund. The institution of Dr. Robbins has received research support from Institute for Ethnomedicine. The institution of Dr. Robbins has received research support from Dartmouth Hitchcock Swigart Ethics Fellowship. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Neurohospitalist with Hayes Locums. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Vickery &amp; Shepherd. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Vaccine Injury Compensation Program. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Kraft Davies PLLC. Dr. Robbins has received personal compensation in the range of $500-$4,999 for serving as a Medical Expert with Northwestern University.

Tofacitinib as monotherapy in cutaneous polyarteritis nodosa: a case series.

Cutaneous polyarteritis nodosa (CPAN) is a distinct clinical entity represented by a chronic, relapsing, benign course, with rare systemic involvement. Treatment is with CSs, CYC or other conventional synthetic DMARDs (csDMARDs). In this case series, we aimed to share our varied clinical experience of successfully treating patients with CPAN, with tofacitinib in a refractory/relapsing course or as upfront monotherapy without CSs/csDMARDs. We report this retrospective case series managed at our rheumatology centre in Bangalore from 2019 to 2022. Four patients identified as CPAN on biopsy were able to achieve disease-free remission with tofacitinib as part of their treatment, with no relapse on further follow-up. Our patients presented with subcutaneous nodules and cutaneous ulcers. After systemic evaluation, all the patients underwent skin biopsy, which showed fibrinoid necrosis in the vessel walls of the dermis, with a histopathological impression of CPAN. They were initially treated with a conventional approach of CSs with/without csDMARDs. On experiencing a refractory/relapsing course, tofacitinib was tried in all the patients as either CS sparing or upfront monotherapy without concomitant csDMARDs. Use of tofacitinib resulted in improvement of ulcers and paraesthesia and in gradual healing of skin lesions, albeit with scarring, with no further recurrence or relapse over a follow-up period of 6 months for all the patients. The therapeutic effect of tofacitinib was consistent when used either as CS sparing or as upfront monotherapy, thereby proving the drug to be a promising option that warrants larger trials in future to treat the subset of patients with established CPAN. Tofacitinib could be used for disease-free remission as monotherapy for CPAN either upfront or as CS sparing, even without concomitant csDMARDs, in those patients who are dependent on CSs or multiple DMARDs.

Skin Biopsies in Gastrointestinal Diseases: A Single Centre Experience from North India

Skin manifestations have always been alarming to the patient and often warrant complete clinical evaluation. A thorough understanding of relationship between gastrointestinal (GI) disorders and skin diseases can alert the clinician to an underlying occult GI disorder. The aim of the study was to review the cutaneous changes in patients with co-existent, often masked GI diseases and to observe the underlying pathophysiology of such lesions. This was a retrospective, record based observational study. The archived histopathology reports &amp; medical records of patients over a period of 5 years were searched and all patients who underwent skin biopsy with co-existent GI diseases were included. Out of a total of 218 patients of GI diseases who had dermatological manifestations, only 44 were biopsied. Pruritis (n=175), koilonychia (n=52) and erythematous rash (n=35) were the most common clinical features. Psoriasis (n=4), vasculitis (n=4), Dermatitis Herpetiformis (n=3) and pyoderma gangrenosum (n=5) were often seen associated with benign GI diseases like Inflammatory Bowel Diseases, Chronic Liver Disease, Malabsorption syndrome etc. Sweets syndrome (n=2) and cutaneous metastatic nodules (n=3) were associated with underlying malignancy particularly of gall bladder and pancreas.

Misfolded α-Synuclein Assessment in the Skin and CSF by RT-QuIC in Isolated REM Sleep Behavior Disorder.

Real-time quaking-induced conversion (RT-QuIC) assay detects misfolded α-synuclein (AS) in the skin and CSF of patients with the synucleinopathies Parkinson disease and dementia with Lewy bodies. Isolated REM sleep behavior disorder (IRBD) constitutes the prodromal stage of these synucleinopathies. We aimed to compare the ability of RT-QuIC to identify AS in the skin and CSF of patients with IRBD. This was a cross-sectional study where consecutive patients with polysomnographic-confirmed IRBD and age-matched controls without RBD underwent skin biopsy and lumbar puncture the same day. Three-millimeter skin punch biopsies were obtained bilaterally in the cervical region from dorsal C7 and C8 dermatomes and in distal legs. RT-QuIC assessed AS in these 6 skin sites and the CSF. We recruited 91 patients with IRBD and 41 controls. In the skin, sensitivity to detect AS was 76.9% (95% CI 66.9-85.1), specificity 97.6% (95% CI 87.1-99.9) positive predictive value 98.6% (95% CI 91.0-99.8), negative predictive value 65.6% (95% CI 56.6-73.6), and accuracy 83.3% (95% CI 75.9-89.3). In the CSF, the sensitivity was 75.0% (95% CI 64.6-83.6), the specificity was 97.5% (95% CI 86.8-99.9), the positive predictive value was 98.5% (95% CI 90.5-99.8), the negative predictive value was 63.9% (95% CI 55.2-71.9), and the accuracy was 82.0% (95% CI 74.3-88.3). Results in the skin and CSF samples showed 99.2% agreement. Compared with negative patients, RT-QuIC AS-positive patients had a higher likelihood ratio of prodromal Parkinson disease (p < 0.001) and showed more frequently hyposmia (p < 0.001), dopamine transporter imaging single-photon emission CT deficit (p = 0.002), and orthostatic hypotension (p = 0.014). No severe or moderate adverse effects were reported. There was no difference between the percentage of participants reporting mild adverse events secondary to skin biopsy or lumbar puncture (9.1% vs 17.2%; p = 0.053). One hundred and ten (83%) and 104 (80%) participants, respectively, stated they would accept to undergo skin biopsy and lumbar puncture again for research purposes. Our study in IRBD shows that (1) RT-QuIC detects AS in the skin and CSF with similar high sensitivity, specificity, and agreement, (2) AS RT-QuIC positivity is associated with supportive features and biomarkers of synucleinopathy, and (3) skin punch biopsy and lumbar puncture have comparable mild adverse effects, tolerance, and acceptance. RT-QuIC in the skin or CSF might represent a patient selection strategy for future neuroprotective trials targeting AS in IRBD. This study provides Class III evidence that RT-QuIC-detected AS in the skin and CSF distinguishes patients with IRBD from controls.

Hypothalamic involvement of sarcoidosis presenting with behavioral disorder

Abstract Introduction Sarcoidosis is an idiopathic, chronic, disease with non-caseating granuloma formation. Central nervous system (CNS) involvement (neurosarcoidosis) is observed in 5–15% of cases. Hypothalamic–pituitary (HP) neurosarcoidosis (NS) accounts for 0.5% cases of sarcoidosis. We present a case of hypothalamic-pituitary sarcoidosis with compulsive behaviors, diabetes insipidus and pan-hypopituitarism. Clinical Case A 43-year-old male patient was admitted to our clinic with complaints of fatigue, polydipsia, erectile dysfunction for 1 month, as well as compulsive behaviors such as excessive shopping, exercise and hyperphagia. In his history, it was learned that he had been diagnosed with sarcoidosis 1 year ago, based on skin biopsy and clinical examination, and discontinued the treatment. On physical examination, erythematous lesions were observed on the face and back. Multiple lymphadenopathies (LAP) of 2 cm in size were palpated in the axilla and inguinal region. The patient's neurological examination was normal. MRI of the brain showed heterogeneous enhancement of the gland parenchyma posteriorly. In sagittal sections, an area that is not contrasted to the gland base is selected. (Fig. 1) The infundibulum is markedly thick and shows enhancement, and in its continuity, similar thickening and enhancement are observed in the hypothalamus. Due to the thickening of the infundibulum, the optic chiasm appears to be spread on both sides. Differential diagnosis was TB, sarcoidosis and lymphoproliferative disease. Pituitary function showed free T4 0.53 ng/ml (normal 0.93–1.7), TSH 0,89 μIU/ml (normal 0.27–4.2), FSH 0.87 milliunit/ml (normal 1–11), LH &amp;lt;0.55 milliunit/ml (normal 1–8), ACTH 1,5 pg/ml (normal 7.2–63), Cortisol 3,59 μg/dl Prolactin 14.3 ng/ml (normal 0.5–17), total testosterone 2,5 ng/ml (normal 37–198). He tested negative for ANA, HIV, Hepatitis C, Mycobacterium TB Interferon-Gamma. The patient underwent skin biopsy and excisional lymph node biopsy. Non-necrotizing granulomas found at biopsy samples. He was started on desmopressin, methylprednisolone, levothyroxine. Patient had significant improvement following treatment. Conclusion Neurosarcoidosis may present with various clinical features depending on the anatomical location of the disease. Hypogonadotropic hypogonadism, diabetes insipidus, amenorrhea and anterior pituitary insufficiency are the most common endocrine findings. Hypothalamic findings such as changes in thirst, disturbance in thermoregulation, changes in appetite and body weight without diabetes insipidus have been reported in case reports. Although it is a rare condition, symptoms of hypothalamic-pituitary changes, can be seen in sarcoidosis and are an indication for treatment. It requires long-term management by a multidisciplinary team of patients.

Observational case-control study of small-fiber neuropathies, with regards on smoking and vitamin D deficiency and other possible causes.

Small fiber neuropathies (SFNs) are disorders of skin nerve endings inducing pruritus, burning pain, numbness, and paresthesia. The aims of this study were to search for putative etiologies of SFN and their occurrence in a cohort of patients and to compare patients with SFN to a group of patients without SFN to highlight potential factors associated with SFN. This study was observational, retrospective, and monocentric. All patients with symptoms of SFN who underwent skin biopsies with intraepidermal nerve density counts were included. Patients with a count lower than 5 percentiles were considered to be in the SFN group. Other patients were considered to be the control group. A total of 162 patients with SFN and 161 controls were included. No cause was identified for 108 patients (61.7%). The established causes were autoimmune diseases (9.1%), diabetes or glucose intolerance (8%), medication (4%), liver disease (3.4%), and monoclonal gammopathy of undetermined significance (2.9%). Current or former smokers were more numerous in the SFN group (26.5%) than in the control group (16.1%), while vitamin D amounts were significantly lower in the SFN group than in the control group. Hence, tobacco smoking and vitamin D deficiency might be new putative causes of SFN.

A Six-Year Retrospective Analysis of Skin Biopsies in the Pediatric and Adolescent Population Performed at a Tertiary Health Care Center in India.

Hesitancy to perform skin biopsies in children or adolescents may lead to delayed diagnosis or misdiagnosis and relatively, few studies analyzing pediatric skin biopsies exist. This study aims to analyze the spectrum of skin diseases biopsied and demographic data of pediatric patients underwent skin biopsies at a tertiary health care center in India. Biopsy records over six years were analyzed, noting demographic data, disease duration, clinical differential diagnoses (CDD), final diagnosis after histopathology, disease categorization, and agreement between clinical and final diagnosis. The mean, range, and statistical significance of differences between proportions were calculated. A total of 1308 biopsy records were analyzed. A male preponderance was noted (males - 55.1%; n = 721, females - 44.9%; n = 587). Most biopsies were performed in adolescents (12-18 years; 55.2%) followed by school-age children (5-12 years; 31.4%). Preponderant disease groups biopsied comprised papulosquamous (17.7%; n = 231) and infectious diseases (14.1%; n = 184). Leprosy was the most common infectious disease (37.5%; n = 69) with most patients belonging to borderline tuberculoid spectrum. The overall diagnostic agreement was 74.7%. No correlation of final diagnosis was noted with the number of CDD offered. In more than a fifth of cases, biopsy averted misdiagnosis. This study highlights the importance of skin biopsies in pediatric patients and the relatively high clinico-histopathologic agreement. Leprosy and papulosquamous diseases were preponderant in the pediatric dermatopathology caseload.

Combination of Fractional Microneedling Radiofrequency and Ablative Fractional Laser versus Ablative Fractional Laser Alone for Acne and Acne Scars.

Fractional microneedle radiofrequency (FMR) systems are used to treat inflammatory acne and scarring. Nonetheless, few controlled studies have combined this treatment with the traditional ablative fractional laser (AFL). We aimed to assess the safety and efficacy of the combination of FMR and AFL versus AFL alone in treating acne and acne scars. In this 20-week, randomized, split-face study, 23 Korean patients with facial acne and acne scars underwent FMR and AFL treatments. One half of each patient's face was randomly assigned to receive FMR+AFL, whereas the other half received AFL alone. Treatments were administered in three consecutive sessions at 4-week intervals. This study investigated the severity of inflammatory acne, acne scars, individual lesion counts, depressed scar volumes, as well as patient and physician satisfaction. In addition, five patients underwent skin biopsy, and sebum output was measured. The FMR+AFL treatment demonstrated superior efficacy compared to AFL alone in terms of inflammatory acne and acne scar grading, lesion counts, and subjective satisfaction. The side effects were minimal and well-tolerated in both groups. Immunohistochemical findings from skin biopsy samples revealed that the application of FMR+AFL could induce an inhibitory effect on sebum secretion at the molecular level. FMR combined with AFL is a well-tolerated and effective treatment modality for inflammatory acne and acne scarring.

Prognostic Significance of Cutaneous Angioimmunoblastic T-Cell Lymphoma: Correlation of Clinical, Histologic and Immunophenotypic Features with Response

Background: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma with a follicular helper T-cell immunophenotype. Up to 50% of AITL patients present with dermatologic manifestations. However, the prognostic implications of clinical, histologic, and immunophenotypic features of cutaneous AITL have not been fully elucidated. Objective: To characterize clinical, histologic, and immunophenotypic features of cutaneous AITL and determine their prognostic significance. Methods: We identified 293 patients seen at our institution diagnosed with AITL by characteristic immunohistochemical markers on lymph node biopsy between 1990 and 2020. Not all patients underwent skin biopsy for their rash, therefore we defined "suspected cutaneous AITL” as cases with documented rash occurring at the time of AITL diagnosis or during the disease course. A subset of cases were defined as "confirmed cutaneous AITL” if they had pathologist confirmed AITL on skin biopsy. Cutaneous presentations were excluded if another etiology, such as drug reaction or skin infection, was determined by clinical history and/or skin biopsy findings. We collected clinical data from patient medical records regarding patient demographics, disease characteristics, and clinical outcomes. The Chi-square test or Fisher's exact test was used to evaluate the association between two categorical variables. Wilcoxon rank sum test was used to evaluate the difference in a continuous variable between patient groups. Kaplan-Meier method was used for time-to-event analysis including progression free survival (PFS) and overall survival (OS). The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Results: Overall, 32% of the patients had suspected cutaneous AITL with various presentations, but most presented with a maculopapular rash (31%) on the legs (16%) that was pruritic (66%) with onset at about 4 months after the AITL diagnosis. Furthermore, 10% of all AITL patients had confirmed cutaneous AITL on skin biopsy, most commonly with a perivascular infiltrative pattern (69%). The median WBC among patients with suspected cutaneous AITL was higher than AITL without skin findings (8.95 vs. 6.3; p-value=0.0036). Otherwise, there were no significant differences in clinical features for suspected or confirmed cutaneous AITL patients. In terms of treatment response, patients without rash had a higher overall response rate (ORR) rate from the second line treatment compared to suspected cutaneous AITL patients (62.5% vs. 41.9%; p-value=0.049). Also, the rate of ORR from upfront treatment was higher among the patients with pruritus compared to the patients without pruritus (65.2% vs. 92.3%; p-value=0.0134). The median OS time for all AITL patients was 35.3 months (95% CI: 31.1 ~ 47 months) with a 5-year OS of 36%. The median follow-up time was 53.5 months (95% CI: 44.1 ~ 64.6 months). There were no significant differences in OS for suspected cutaneous AITL or confirmed cutaneous AITL patients. The median PFS time was 12.8 months (95% CI: 10.4 ~ 17.5 months) with a 5-year PFS of 19%. Conclusion: Our study corroborates the aggressive nature of AITL and its poor prognosis. AITL patients with pruritus may respond more favorably to upfront treatment, while AITL without skin involvement may respond better to second line treatment. However, we found no significant association between skin involvement and survival. Moreover, no histologic or immunophenotypic features in the skin were identified with prognostic value. Continued examination of disease characteristics for prognostic significance can serve to enhance the care for these patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Development of a Comprehensive Program for Evaluation of Hereditary Predisposition to Hematologic Malignancies

Introduction Germline pathogenic variants underlie or contribute to an estimated 20% of leukemia and up to 50% of aplastic anemia. Early diagnosis of inherited predisposition to hematologic malignancy (IPHM) and bone marrow failure is critical for treatment planning both due to the risk of subjecting patients to excessive toxicity from standard doses of chemotherapy or radiation and because affected relatives who are potential donors for stem cell transplant (SCT) should be identified. Further, identification of associated risks for other non-hematologic cancers and multisystem diseases provide opportunities for screening, monitoring, and early treatment. Family members may also be at risk for complications related to the IPHM identified in the proband and therefore are candidates for screening with counseling and surveillance. Methods We established a multicenter collaborative program between three hospitals [Huntsman Cancer Institute at University of Utah, LDS Hospital at Intermountain Healthcare, and Primary Children's Hospital (all in Salt Lake City, UT)] with specific criteria for genetic evaluation defined prospectively (Table 1). All patients identified for evaluation were assessed by a certified genetic counselor. Germline genetic testing was performed using DNA from culture fibroblast derived from skin biopsies. Laboratory selection for germline genetic testing was based on the patient's insurance coverage, admission status, personal history, family history, requested turnaround time, time to SCT, and comprehensiveness of panel. Germline genetic testing was performed at one of the following laboratories: Prevention Genetics, GeneDX Laboratories, ARUP Laboratories, Ambry Genetics, and Invitae Genetics. Chromosome breakage analysis and telomere length measurement were performed on patients with clinical suspicion of Fanconi anemia or a telomere biology disorder, respectively. Results Between October 2021 and April 2022, 61 patients were identified prospectively who met evaluation criteria for referral to genetic counseling (Table). Of these patients, 42 were males and 19 were females. Median age was 35 years (range newborn to 77 years). The most common reasons for evaluation were cytopenia (n=14), myelodysplastic syndrome (n=10), and acute myeloid leukemia (n=16). Four potential SCT donors were evaluated. Of 61 patients, 60 patients were referred directly to a genetic counselor. Of the 58 patients who kept their appointment (58/61, 95%), the median time from referral to clinic evaluation was 6 days (range, same day to 99 days,). Fifty-two patients underwent genetic testing with 47 having panel testing and 5 having gene specific testing. Twenty-nine patients underwent skin biopsy (all hematologic malignancies and one case of aplastic anemia), and 23 patients underwent testing on saliva or blood samples. Of the 52 patients who underwent germline genetic testing, eight were found to have pathogenic/likely pathogenic variants and eight were identified with suspicious variants of uncertain significance (Table 2). Identification of 16 patients with pathogenic or suspicious genetic test results led to testing of four potential HSCT donors. Conclusion The results of this study show the feasibility of developing a comprehensive, collaborative program for evaluation of IPHM. Essential to the success of such a program is a genetic counselor who is readily available for consultation and whose breath of knowledge is sufficient both to guide patient evaluation and to interpret findings that impact directly on management of patients and family members. Other important contributors to program success include active communication with pediatric and adult clinicians who treat patients with hematologic malignancies and bone marrow failure, and laboratory support for obtaining skin biopsies, culturing fibroblasts, and extracting and preserving DNA. Our program can serve as a blueprint for establishing a service line for comprehensive germline testing for IPHM at other medical centers. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Skin Biopsy and Quantitative Sudomotor Axon Reflex Testing in Patients With Postural Orthostatic Tachycardia Syndrome.

No formal diagnostic criteria exist for the neuropathic subtype of postural orthostatic tachycardia syndrome (POTS). Skin biopsy and quantitative sudomotor axon reflex testing (QSORT) are preferred methods of assessment for autonomic small fiber neuropathy (SFN). This study characterizes the utility of these testing methods at a tertiary center and identifies clinical features associated with abnormal testing. Medical records of 2658 patients undergoing tilt table testing at a single institution between June 2018 and December 2020 were reviewed. Patients with postural orthostatic tachycardia syndrome were included for analysis of intraepidermal nerve fiber density (IENFD), sweat output, comorbidities, symptoms, measures of cardiovascular autonomic function, and serum antibody levels. 356 patients (90% female, mean age 31 ± 10) met the diagnostic criteria for postural orthostatic tachycardia syndrome. Of 211 patients who underwent quantitative sudomotor axon reflex testing, 70 (33%) demonstrated reduced sweat output. These patients were more likely to demonstrate sympathetic impairment during the Valsalva maneuver. Of 80 patients who underwent skin biopsies, 19 (24%) demonstrated reduced intraepidermal nerve fiber density. These patients tended to be older and have reduced heart rate variability during deep breathing. Neither test was associated with specific serum antibodies, symptoms, or comorbidities, though there was a trend toward higher rates of comorbid autoimmune disease in patients with abnormal testing. A subset of patients with postural orthostatic tachycardia syndrome have evidence of small fiber neuropathy. These patients tend to have impaired cardiovascular autonomic function but are otherwise similar to patients with no evidence of small fiber neuropathy.

Skin Biopsy as a Novel Diagnostic Aid in Immune-Mediated Neuropathies.

Immune-mediated neuropathies are a heterogenous group of inflammatory peripheral nerve disorders. They can be classified according to the domain where the autoimmune process begins: the internode, paranode, or node. However, conventional diagnostic tools, electrodiagnosis (EDX), and autoantibody testing do not fully address this issue. In this institutional cohort study, we investigated the value of dermal myelinated fiber analysis for target domain-based classification. Twenty-seven consecutive patients with immune-mediated neuropathies underwent skin biopsies. The sections were stained with antibodies representative of myelinated fiber domains and were scanned using a confocal microscope. Clinical and pathological features of each patient were reviewed comprehensively. Quantitative morphometric parameters were subjected to clustering analysis, which stratified patients into 3 groups. Cluster 1 ("internodopathy") was characterized by prominent internodal disruption, intact nodes and paranodes, demyelinating EDX pattern, and absence of nodal-paranodal antibodies. Cluster 2 ("paranodopathy") was characterized by paranodal disruption and corresponding antibodies. Morphological changes were restricted to the nodes in cluster 3; we designated this cluster as "nodopathy." This report highlights the utility of skin biopsy as a diagnostic aid to gain pathogenic insight and classify patients with immune-mediated neuropathies.

33527 What is the most effective picosecond laser protocol for tattoo removal? A comparative study by histopathologic review

Background: Picosecond lasers have become widely adapted as the mainstay of tattoo removal due to their faster heating of target chromophores and consequently more effective tattoo removal. Different protocols for tattoo removal using the picosecond laser are actively being studied. Our investigation focuses on the R20 method: repeated exposure to laser light at 20-minute intervals in a single session. Several preliminary studies have shown that R20 technique could be effective in reducing treatment time while maintaining efficacy. Objective: This study aims to compare different picosecond laser techniques in clearing tattoos. Methods and materials: Three patients with tattoos (1 on foot, 2 on arms) underwent skin biopsy followed by laser tattoo removal. The target site was divided into 4 areas, each of which received different protocols: picosecond laser alone, R20 method, picosecond MLA followed by picosecond toning, and picosecond laser after gel application. The protocols were all performed five times at 1-month intervals. After treatment completion, 1 patient underwent biopsy of all four treatment sites while the other 2 underwent biopsy only at the R20 treatment area. Results: Histopathologic evaluation showed that the R20 treatment site had the least remaining intradermal pigmentation. Picosecond MLA followed by picosecond toning laser was shown to have the following best outcome. Conclusion: Our report compares skin biopsy findings before and after laser treatment and clinical results for tattoo removal. Although the number of cases is small, our preliminary findings suggest that the Pico R20 is favorable for tattoo removal.

Clinical triad with multi-biopsy histopathology as a reliable diagnostic marker of mycetomas: a retrospective review from a tertiary care center.

Mycetoma is a neglected tropical infectious disease which runs a prolonged and protracted course. Microbiological confirmation is diagnostic yet unreliable due to poor sensitivity and variable availability of culture facilities in resource poor settings. A retrospective review was performed on electronic records (histopathology, microbiology, and radiology) of all patients who underwent skin biopsies with mycetoma as one of the clinical differential diagnoses from year 2016 to 2020. Out of 73 patients biopsied with a differential of mycetoma, 42 fit the clinical triad of swelling-sinuses-granules. After clinical, microbiological, pathological, and radiological correlation, 31 cases were of eumycetoma and seven were of actinomycetoma. Mean patient age was 37.58 ± 13.8 years with a male to female ratio 2.45 : 1 and mean disease duration of 11.31 ± 10.9 years. Histopathological findings revealed fungal hyphae in 18 cases and gram-positive bacteria in six cases. Fungal culture was positive in 13 cases with the three commonest organisms being Madurella mycetomatis in five cases, Fusarium and Aspergillus nidulans in two cases each. X-ray changes of soft tissue, bones, and joints were seen in 25 cases, and "dot-in-circle" sign was seen in eight of nine MRIs. Eumycetoma was more common than actinomycetoma in our setup, ratio being 4.43 : 1. A clinical triad of swelling, multiple sinuses and grainy discharge with any one diagnostic support (histopathology/radiology) is sufficient to make a definitive diagnosis of mycetoma in the absence of microbiological identification.

Proportion of psoriasis among the patients with psoriasiform disorders

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Psoriasis is a prevalent chronic inflammatory skin disease with several clinical symptoms. Psoriasis has clinical forms that resemble a variety of dermatological disorders and may necessitate histological confirmation of the diagnosis. The aim of the study was to assess the proportion of psoriasis among patients with psoriasiform disorders.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This cross-sectional observational study was carried out at the department of dermatology and venereology, Shahid Syed Nazrul Islam Medical College, Kishoreganj during the period from January 2021 to December 2021 on 200 patients with psoriasiform disorders was enrolled in this study. Detailed history along with relevant family history and drug history was obtained. All the patients underwent skin biopsy followed by a histopathological examination to reveal the actual pathology of dermal lesions. Statistical analyses of the results were obtained by using window-based computer software devised with statistical packages for social sciences (SPSS-25).&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The proportion of psoriasis among the patients with psoriasiform disorders was found at 53.5%. The majority of patients (72.0%) had extensor surfaces and a well-demarcated border was found in 166 (83.0%) patients. Subungual hyperkeratosis was found in 30 (28.0%) and 16 (17.3%) in psoriasis and non-psoriasis groups respectively. Regular epidermal hyperplasia was 2 (1.9%) in psoriasis but not found in non-psoriasis. Spongiosis was 45 (42.1%) in psoriasis and 30 (32.3%) in non-psoriasis. The vertical orientation of the collagen bundle was 2 (1.9%) and 2 (2.2%) in psoriasis and non-psoriasis respectively. Perivascular lymphocyte infiltration was 75 (70.1%) in psoriasis and 63 (67.7%) in non-psoriasis. The difference was not statistically significant (p&amp;gt;0.05) between the two groups.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; All clinical features were significantly associated with psoriasis in patients who presented with psoriasiform disorders except subungual hyperkeratosis. In histopathology, all features were significantly associated with psoriasis excluding regular epidermal hyperplasia, spongiosis, vertical orientation of collagen bundle, and perivascular lymphocyte infiltration.&lt;/p&gt;

Proton pump inhibitor induced subacute cutaneous lupus erythematosus: Clinical characteristics and outcomes.

There is a growing literature reporting the association between proton pump inhibitor (PPI) use and subacute cutaneous lupus erythematosus (SCLE). To compare the clinical characteristics of a cohort of patients with PPI-induced SCLE, their clinical course and treatment with a control group of primary SCLE patients not exposed to PPI. We conducted a matched case-control study in a tertiary referral setting at the Louise Coote Lupus Unit. There were 64 SCLE patients: 36 with PPI-induced SCLE and 28 patients with primary SCLE. Twenty-six patients (72%) had pre-existing SLE in the PPI-induced SCLE group. Lower limb skin lesions were significantly more prevalent in the PPI group (p < 0.0001). The prevalence of anti-Ro and anti-Ro-52 antibodies was numerically higher in the PPI group (64% and 60%), respectively, compared with 46% and 42% in the primary SCLE group. Peripheral blood eosinophils were normal in all patients in the PPI group. Thirteen patients underwent skin biopsy in the PPI group and 12 had histology in keeping with SCLE. The median time to presentation was 8months with a median resolution period of 6 weeks. PPIs were stopped in 34 patients, while 2 patients continued treatment for other clinical indications. Twelve patients received concurrent oral corticosteroids. Two patients had severe SCLE in the form of Toxic Epidermal Necrolysis requiring critical care admission and were managed with corticosteroids, IV immunoglobulin and/or belimumab. Lower limb involvement is a pointer to PPI-induced SCLE which is likely a class effect with all PPI.

Skin amyloid deposits and nerve fiber loss as markers of neuropathy onset and progression in hereditary transthyretin amyloidosis.

This study was undertaken to assess skin biopsy as a marker of disease onset and severity in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), a treatable disease. In this single center retrospective study, skin Congo red staining and intraepidermal nerve fiber density (IENFD) were evaluated in symptomatic ATTRv-PN patients and asymptomatic TTR gene mutation carriers between 2012 and 2019. Non-ATTRv subjects with suspected small fiber neuropathy who underwent skin biopsy during the same timespan were used as controls. One hundred eighty-three symptomatic ATTRv-PN patients, 36 asymptomatic carriers, and 537 non-ATTRv patients were included. Skin biopsy demonstrated amyloid depositions in 80% of the 183 symptomatic cases. Skin amyloid deposits were found in 75% of early stage ATTRv-PN patients, and in 14% of asymptomatic carriers. All 183 symptomatic and 34 of 36 asymptomatic patients displayed decreased ankle IENFD with a proximal-distal gradient distribution, and reduced IEFND correlated with disease severity and duration. Our study demonstrates skin amyloid deposits are a marker of ATTRv-PN disease onset, and decreased IENFD a marker of disease progression. These results are of major importance for the early identification of ATTRv-PN patients in need of disease-modifying treatments.

Presence of Skin α-Synuclein Deposits Discriminates Parkinson's Disease from Progressive Supranuclear Palsy and Corticobasal Syndrome.

Background:Previous studies reported skin phosphorylated α-synuclein (p-syn) deposits in Parkinson’s disease (PD) patients but not in patients with parkinsonism due to tauopathies, although data on the latter are limited.Objective:We aimed to assess the presence of skin p-syn deposits in patients with clinical diagnosis of parkinsonism usually due to tauopathy and PD.Methods:We consecutively recruited 26 patients, 18 fulfilling clinical diagnostic criteria of progressive supranuclear palsy (PSP) and 8 of corticobasal syndrome (CBS), 26 patients with PD, and 26 healthy controls (HC). All subjects underwent skin biopsy to study p-syn deposits in skin nerves by immunofluorescence.Results:Skin p-syn deposits were present in only two of the PSP/CBS patients and none of the HC. Conversely, all PD patients showed p-syn deposition (p < 0.001, Chi-square). The two p-syn positive patients were diagnosed with PSP and CBS, respectively. Although clinical and MRI findings supported these diagnoses, both patients had some atypical features more typical of synucleinopathies.Conclusion:The detection of skin p-syn deposits may help in the differential diagnosis of parkinsonism. Indeed, in this study, all PD patients and only two out of 26 with a clinical diagnosis of PSP/CBS had skin p-syn deposits. Furthermore, these two patients showed clinical features that could suggest an atypical synucleinopathy presentation or a mixed pathology.

Neuronal intranuclear inclusion disease tremor-dominant subtype: A mimicker of essential tremor.

The GGC repeat expansion in the NOTCH2NLC gene has been identified as the genetic cause of neuronal intranuclear inclusion disease (NIID). Recently, this repeat expansion was also reported to be associated with essential tremor (ET). However, some patients with this repeat expansion, initially diagnosed with ET, were eventually diagnosed with NIID. Therefore, controversy remains regarding the clinical diagnosis of these expansion-positive patients presenting with tremor-dominant symptoms. This study aimed to clarify the clinical phenotype in tremor-dominant patients who have the GGC repeat expansion in the NOTCH2NLC gene. We screened for pathogenic GGC repeat expansions in 602 patients initially diagnosed with ET and systematically re-evaluated the clinical features of the expansion-positive probands and their family members. Pathogenic GGC repeat expansion in the NOTCH2NLC gene was detected in 10 probands (1.66%). Seven of these probands were re-evaluated and found to have systemic areflexia, cognitive impairment, and abnormal nerve conduction, which prompted a change of diagnosis from ET to NIID. Three of the probands had typical hyperintensity in the corticomedullary junction on diffusion-weighted imaging. Intranuclear inclusions were detected in all four probands who underwent skin biopsy. The NIID tremor-dominant subtype can be easily misdiagnosed as ET. We should take NIID into account for differential diagnosis of ET. Systemic areflexia could be an important clinical clue suggesting that cranial magnetic resonance imaging examination, or even further genetic testing and skin biopsy examination, should be used to confirm the diagnosis of NIID.

Detection rate of pustules in palmoplantar pustulosis with dermoscopy.

In this study, dermoscopy was applied to determine the site of skin biopsy in cases of palmoplantar pustulosis (PPP) with invisible tiny pustules or vesicles. Fifty-two clinically diagnosed PPP patients (11 men and 41 women) were observed by a dermoscope and underwent skin biopsy. Nineteen patients had visible pustules, whereas 33 had no visible pustules. Pustules were detected by a dermoscope on palmoplantar lesions in 17 of the 33 PPP patients. In contrast, 16 patients showed no presence of pustules or vesicles observed by a dermoscope. In this group, biopsy specimens were taken from scaly lesions. Out of the 16 patients, 10 histologically showed pustules in the epidermis. We finally detected pustules for 46 patients among 52 who were clinically diagnosed with PPP. As a result, we detected pustules in PPP for 19 patients on "inspection", and 36 patients on "inspection and dermoscopy", and 46 patients on "inspection, dermoscopy, and biopsy". Dermoscopy is significantly useful comparing the detection rate (inspection, 0.41; inspection and dermoscopy, 0.78; p=0.0003; using χ2 -test). In addition, we also should learn from the results that the detection rate goes down to 0.78 without a biopsy. Thus, dermoscopy is certainly a useful tool for invisible pustules and also undetectable pustules to detect pustules in PPP. Moreover, we objectively showed that "inspection, dermoscopy, and biopsy" are the best way to make a PPP diagnosis.