Quantitative sensory testing in notalgia paresthetica reveals small fiber-type-specific differences in non-pruritic sensitivity: a pilot study.

Introduction: Notalgia paresthetica (NP) is a chronic condition characterized by pruritus and other unpleasant dysesthetic sensations unilaterally on the subscapular back. Its specific underlying mechanisms are largely unknown, though hypothesized to be neuropathic. Determination of possible somatosensory contributors to the condition could pave the way for novel treatments. Objectives: Given the potential involvement of non-pruritic mechanisms in NP, our objective was to broadly characterize the somatosensory function in NP-affected and unaffected skin using methods that have been standardized in pain-free controls and painful neuropathic disorders. We hypothesized that if NP is caused by neuropathic mechanisms not targeted directly to pruritoceptors in the skin, somatosensory abnormalities would not be itchspecific. Second, given the lack of symptoms on the contralateral side of the back, we hypothesized that this region would be normally sensitive. Methods: In this study, quantitative sensory testing (QST) was used to comprehensively assess the somatosensory function in 15 adult patients with NP. Standardized QST metrics were performed in the NP-affected region and compared with the contralateral asymptomatic skin and itch-free individuals using an age, gender, and site-matched reference data set. Results: There were no significant differences in sensitivity between symptomatic and asymptomatic skin, except for increased mechanical-evoked itch on the itchy side. However, reference data set comparisons revealed bilateral hyposensitivity to innocuous cold and noxious pinprick and higher temporal summation of pain in patients with NP. In addition, compared with reference data, patients with NP demonstrated decreased sensitivity to cold and pinprick, presence of paradoxical heat sensations, and increased wind-up of pain. Conclusion: These results suggest a role for Aδ fiber pathways and central sensitization in NP-associated itch. More research is needed to determine whether sensory differences extend beyond the NP-affected dermatomal level and what might cause neuropathy specifically targeting Aδ fibers.

Comparing Clinical Outcomes of Steroid-Sparing Therapy With Rituximab Versus Rituximab Alone in Pemphigus.

BACKGROUND: Previous clinical trials have demonstrated that rituximab therapy combined with conventional steroid-sparing therapy (SST) has increased rates of disease control for mucous membrane pemphigoid compared with rituximab alone. However, limited data is available regarding the role of SST with rituximab therapy in pemphigus. OBJECTIVE: This study aimed to examine clinical outcomes in pemphigus patients treated with rituximab with SST versus without the addition of SST. METHODS: A retrospective chart review was performed for adult pemphigus patients in the Southeastern US at Emory between January 1, 2011, and December 31, 2021. Primary outcomes, including time to remission, time to prednisone dose of 10 mg or less, time to cessation of prednisone therapy, and time to relapse after a rituximab cycle, were compared between patients on SST and patients without SST.  Results: Following rituximab therapy, there was no difference in time to remission, time to prednisone dose of 10 mg or less, time to cessation of prednisone therapy, or time to relapse for patients with or without SST. LIMITATIONS: Our study is limited by its retrospective decline, setting at a single academic center, and inclusion of a high proportion of patients with moderate disease. CONCLUSIONS: The use of SST with rituximab dosing did not improve clinical outcomes related to time to remission, reduction in prednisone dosing, or relapse. These data provide further evidence for the use of rituximab in the majority of pemphigus patients without the need for SST. J Drugs Dermatol. 2024;23(3):e97-e99    doi:10.36849/JDD.7949e.

Correlation between PainDETECT Questionnaire and Quantitative Sensory Testing for the Detection of Neuropathic Pain in Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that is often severely painful due to nociceptive mechanisms (i.e., stimulation of cutaneous nociceptors). However, patient-reported pain character suggests that neuropathy may also drive HS pain in a subset of patients. Quantitative sensory testing (QST) can help identify neuropathic pain by testing for heightened and paradoxical pain responses in patients, but it is less feasible for routine clinical use compared with brief questionnaires. We therefore tested the suitability of a standardized neuropathic questionnaire (PainDETECT; PD-Q) for use as a surrogate clinical measure by directly comparing it with QST-identified neuropathic pain in HS. METHODS: This observational, cross-sectional study included 22 adults with painful HS lesions who completed the PD-Q and underwent QST. A receiver operating characteristic curve was generated and Cohen's Kappa, sensitivity, and specificity were examined at three scoring thresholds. RESULTS: Of the 22 participants, 14 (64%) exhibited dynamic mechanical allodynia and/or paradoxical thermal sensations in QST, which are characteristically found in neuropathic pain. According to the PD-Q, 8 participants (36%) were unlikely, 8 (36%) were possible, and 6 (27%) were likely to have neuropathic pain. A PD-Q Score indicating possible or likely neuropathic pain (i.e., ≥13) demonstrated 82% agreement with QST-determined neuropathic pain (Cohen's Kappa = 0.61 [p = 0.004]; sensitivity = 86%; specificity = 75%). CONCLUSION: The PD-Q demonstrates moderate agreement with QST in screening for neuropathic pain in HS and may be a helpful clinical tool.

Preordering Periodic Acid-Schiff Staining: A Quality Improvement Study.

ABSTRACT: Periodic acid-Schiff (PAS) stain is a commonly used ancillary test for inflammatory and infectious dermatoses, yet infrequently changes the diagnosis. Previous studies have shown that clinical suspicion and histopathologic features are poor predictors of PAS positivity. Current appropriate use criteria from the American Society of Dermatopathology supports PAS staining when histopathologic features could be consistent with a dermatophyte infection. At the authors' institution, PAS stains are preordered on biopsies of inflammatory and infectious diagnoses to aid in a timelier sign out. Our aim was to reduce the percentage of PAS stains preordered on all dermatology specimens over a 6-month period without reducing the percentage of fungal infections identified. Review of a 12-month preintervention period found that our laboratory received 6104 biopsies for which PAS stain was preordered on 616 (10.1%). Based on a review of the preintervention period, preordering PAS on cases with clinical suspicion for cutaneous T-cell lymphoma was stopped unless there was clinical suspicion for eczematous dermatitis, vesiculobullous disorders, or fungal infection. The proposed intervention resulted in a 3.7% reduction in the number of PAS stains ordered while PAS-positivity rate remained unchanged. The described quality improvement process may be used as a model for other laboratories.

Quantitative Sensory Testing to Characterize Sensory Changes in Hidradenitis Suppurativa Skin Lesions.

Importance: Pain is the most impactful symptom in patients with hidradenitis suppurativa (HS). Characterization of sensory profiles may improve understanding of pain mechanisms in HS and facilitate identification of effective pain management strategies. Objective: To characterize somatosensory profiles in patients with HS at clinically affected and nonaffected sites compared with pain-free reference data. Design, Setting, and Participants: This cross-sectional study was conducted at the Emory University Dermatology Clinic. It was hypothesized (1) that patients with HS would demonstrate hypersensitivity to pain in HS lesions and (2) that some patients would have sensory profiles consistent with complex pain mechanisms. Therefore, adults with dermatologist-diagnosed HS and at least 1 painful HS lesion at the time of testing were enrolled between September 10, 2020, and March 21, 2022. Patients with other diagnoses contributing to pain or neuropathy were excluded. Data analysis was conducted between March and April 2022. Exposure: Quantitative sensory testing was performed on HS lesions and control skin according to a standardized protocol. Main Outcomes and Measures: Quantitative sensory testing outcomes included innocuous thermal and mechanical sensitivity (cold, warmth, and light touch detection thresholds), noxious thermal and mechanical sensitivity (cold, heat, pinprick, and deep pressure pain thresholds and suprathreshold pinprick sensitivity), temporal summation of pinprick, paradoxical thermal sensations, and dynamic mechanical allodynia (pain upon light stroking of the skin). Sensitivity in HS lesions was compared with sensitivity in a control location (the hand) and in pain-free controls using t tests. Results: This study included 20 participants with a median age of 35.5 (IQR, 30.0-46.5) years, the majority of whom were women (15 [75%]). In terms of race and ethnicity, 2 participants (10%) self-identified as Asian, 11 (55%) as Black, 6 (30%) as White, and 1 (5%) as more than 1 race or ethnicity. Compared with site-specific reference values from healthy, pain-free control participants, HS lesions were insensitive to innocuous cold and warmth, noxious heat, and light touch (t = -5.69, -10.20, -3.84, and 4.46, respectively; all P < .001). In contrast, HS lesions also demonstrated significant hypersensitivity to deep pressure pain (t = 8.36; P < .001) and cutaneous pinprick (t = 2.07; P = .046). Hypersensitivity to deep pressure pain was also observed in the control site (t = 5.85; P < .001). A subset of patients with HS displayed changes in pain processing that are often seen in neuropathic and nociplastic pain conditions, including hypersensitivity to repetitive pinprick (5 [26%]), paradoxical thermal sensations (3 [15%]), and pain upon light stroking of the skin (10 [50%]). Conclusions and Relevance: The findings of this cross-sectional study suggest that HS involves local changes in the skin or its free nerve endings, possibly leading to peripheral neuropathy and alterations in the transduction of innocuous and noxious thermal and mechanical stimuli. For some patients, central nervous system changes in somatosensory processing may also occur, but confirmatory evidence is needed. Better understanding of neuropathic and nociplastic mechanisms in HS pain could lead to individually tailored treatments.

An oral lesion masquerading as lichen planus.

Proliferative verrucous leukoplakia (PVL) is a rare, aggressive form of oral leukoplakia with a substantial risk of malignant transformation. The slowly progressive course and the lack of a single defining histopathologic characteristic for PVL make this entity a diagnostic challenge. We report on a patient who presented with a 7-year history of worsening oral lesions.

Early experience with robotic central pancreatectomy with patient-reported outcomes and comparison with open central pancreatectomy.

BACKGROUND: Robotic central pancreatectomy (CP) has emerged in recent years as a noninferior approach to open CP and may offer improved patient-reported outcomes and reduction in incisional hernias. METHODS: All patients who underwent open and robotic CP between (2013 and 2022) were selected, and perioperative outcomes were analyzed. Patients who underwent robotic CP were interviewed over the phone to assess patient-reported postoperative outcomes. RESULTS: A total of 18 CP operations (56%-open vs. 44%-robotic) were identified. The overall median age was 67 years (interquartile range: 60-72), and 50% (n = 9) of patients were female. Median length of surgery was statistically longer for robotic CP (411 vs. 138 min, p = 0.002); all other intraoperative variables were similar. Postoperatively, a similar number of patients in the open and robotic cohorts developed clinically significant postoperative pancreatic fistulas (37.5% vs. 30%, p = 1) and major complications (37.5% vs. 20%, p = 0.60), respectively. No patients in the robotic cohort developed an incisional hernia, compared to 40% (n = 4) in open (p = 0.08). All patients returned to a baseline level of activity and reported a high quality of life. CONCLUSION: With the exception of longer operative times, robotic CP is a noninferior, definitive resection technique for select lesions of the middle pancreas. Additionally, the robotic approach may result in a reduction in incisional hernia development.

A review of pediatric macromastia etiology and indications for reduction mammaplasty.

BACKGROUND: Macromastia in adolescents is both physically and psychologically debilitating during a period in life when individuals are particularly vulnerable to peer pressure and social norms. Early recognition and intervention by both pediatricians and surgeons are critical to avoid unnecessary suffering. While reduction mammaplasty is the gold standard for the management of symptomatic macromastia in adults, the management of macromastia in pediatric patients remains controversial. In particular, there is great discussion regarding the timing of reconstructive breast surgery in pediatric patients. METHODS: A comprehensive review of the literature was performed to identify all articles related to macromastia in patients ≤16 years of age, the age at which full development is typically achieved in the United States. The etiologies of pediatric macromastia, approaches to management, and outcomes are summarized herein. FINDINGS: Pathological breast hypertrophy in pediatric patients is a rare finding and may occur secondary to juvenile hypertrophy of the breast (JHB) and pseudoangiomatous stromal hyperplasia (PASH). While medical management of these pathologies has been attempted with varying success, reduction mammaplasty is safe and effective in pediatric patients. There are, however, a number of pediatric-specific considerations that must be taken into account prior to surgery. We provide an algorithm for approaching pediatric macromastia.

Relationship between Cancer Diagnosis and Complications Following Pancreatoduodenectomy for Duodenal Adenoma.

BACKGROUND: Pancreatoduodenectomy (PD) for duodenal adenoma (DA) resection may be associated with excessive surgical risk for patients with potentially benign lesions, given the absence of pancreatic duct obstruction. We examined factors associated with final malignant pathology and evaluated the postoperative course of patients with DA versus pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively analyzed patients with DA who underwent PD from 2008 to 2018 and assessed the accuracy rate of preoperative biopsy and factors associated with final malignant pathology. Complications for DA patients were compared with those of matched PDAC patients. RESULTS: Forty-five consecutive patients who underwent PD for DA were identified, and the preoperative biopsy false negative rate was 29. Factors associated with final malignant pathology included age over 70 years, preoperative biliary obstruction, and common bile duct diameter > 8 mm (p < 0.05). Compared with patients with PDAC (n = 302), DA patients experienced more major complications (31% vs. 15%, p < 0.01), more grade C postoperative pancreatic fistulas (9% vs. 1%, p < 0.01), and greater mortality (7% vs. 2%, p < 0.05). Propensity score matched patients with DA had more major complications following PD (32% vs. 12%, p < 0.05). CONCLUSIONS: Preoperative biopsy of duodenal adenomas is associated with a high false-negative rate for malignancy, and PD for DA is associated with higher complication rates than PD for PDAC. These results aid discussion among patients and surgeons who are considering observation versus PD for DA, especially in younger patients without biliary obstruction, who are less likely to harbor malignancy.

High-throughput sequencing of murine immunoglobulin heavy chain repertoires using single side unique molecular identifiers on an Ion Torrent PGM.

With the advent of high-throughput sequencing (HTS), profiling immunoglobulin (IG) repertoires has become an essential part of immunological research. Advances in sequencing technology enable the IonTorrent Personal Genome Machine (PGM) to cover the full-length of IG mRNA transcripts. Nucleotide insertions and deletions (indels) are the dominant errors of the PGM sequencing platform and can critically influence IG repertoire assessments. Here, we present a PGM-tailored IG repertoire sequencing approach combining error correction through unique molecular identifier (UID) barcoding and indel detection through ImMunoGeneTics (IMGT), the most commonly used sequence alignment database for IG sequences. Using artificially falsified sequences for benchmarking, we found that IMGT's underlying algorithms efficiently detect 98% of the introduced indels. Undetected indels are either located at the end of the sequences or produce masked frameshifts with an insertion and deletion in close proximity. The complementary determining regions 3 (CDR3s) are returned correct for up to 3 insertions or 3 deletions through conservative culling. We further show, that our PGM-tailored unique molecular identifiers result in highly accurate HTS data if combined with the presented processing strategy. In this regard, considering sequences with at least two copies from datasets with UID families of minimum 3 reads result in correct sequences with over 99% confidence. Finally, we show that the protocol can readily be used to generate homogenous datasets for bulk sequencing of murine bone marrow samples. Taken together, this approach will help to establish benchtop-scale sequencing of IG heavy chain transcripts in the field of IG repertoire research.

Class IC antiarrhythmic drugs for suspected premature ventricular contraction-induced cardiomyopathy.

BACKGROUND: Class IC antiarrhythmic drugs (IC-AADs) can effectively suppress premature ventricular contractions (PVCs). However, IC-AADs increase mortality in patients with PVCs and left ventricular dysfunction after myocardial infarction. Whether IC-AADs can be safely used to treat premature ventricular contraction-induced cardiomyopathy (PVC-CM) remains to be established. OBJECTIVE: The purpose of this study was to determine the safety and efficacy of IC-AADs in patients suspected of having PVC-CM. METHODS: The electronic medical records at the Hospital of the University of Pennsylvania were screened to identify all patients suspected of having PVC-CM treated with flecainide or propafenone. Clinical, electrocardiographic, and imaging studies were reviewed. RESULTS: Twenty patients suspected of having PVC-CM were treated with IC-AADs. Patients had undergone an average of 1.3 ± 0.2 previous unsuccessful ablations. Six had an implantable or wearable defibrillator. With IC-AAD treatment, mean PVC burden decreased from 36.2% ± 3.5% to 10.0% ± 2.4% (P <.001). Mean left ventricular ejection fraction (LVEF) increased from 37.4% ± 2.0% to 49.0% ± 1.9% (P <.001). Seven patients with myocardial delayed enhancement on cardiac magnetic resonance imaging (all <5% of the total myocardium) experienced similar improvement in LVEF (from 36.8% ± 4.3% before IC-AAD to 51.7% ± 3.7% afterward; P <.01). Over an average 3.8 ± 0.9 treatment-years, no sustained ventricular arrhythmias or sudden cardiac deaths occurred. CONCLUSION: In patients suspected of having PVC-CM, IC-AADs effectively suppressed PVCs, leading to LVEF recovery in the majority. No adverse events occurred in this small cohort.