Management of pyoderma gangrenosum during pregnancy and breastfeeding: a systematic review.

Pregnancy is a conjectured risk factor for pyoderma gangrenosum (PG), an autoinflammatory neutrophilic dermatosis characterized by painful ulcers. Even so, there are no available treatment guidelines for those with PG who are pregnant or breastfeeding. To describe existing treatment options, we systematically reviewed the literature on PG treatment in pregnant or breastfeeding patients. A search over four databases was completed in October 2022. Independent reviewers accomplished screening and data extraction. 18 articles met the inclusion criteria. 15 cases involved the treatment of PG during pregnancy, and three cases involved the treatment of PG while breastfeeding. Most patients did not have a history of PG prior to pregnancy (77.7%), and most did not have PG-associated comorbidity (61.1%). Of the cases involving treatment of PG during pregnancy, the majority (73%) found treatment success with a systemic corticosteroid (SCS). Only three cases reported an adverse outcome, including premature rupture of membranes and premature birth (16.7%); all these cases involved treatment with a SCS at >0.5 mg/kg/day during pregnancy. We present a treatment algorithm for pregnant or breastfeeding patients with PG. Our findings suggest prioritizing topicals and TNF inhibitors due to more favorable side effect profiles. However, there is a paucity of data on the safety of PG therapies in pregnancy and breastfeeding, and thus, controlled studies and pregnancy registries must be pursued.

Evaluation of Cannabis-Related Product Use Among Patients With Hidradenitis Suppurativa: A Narrative Review.

The use of cannabis and cannabis-related products among patients with hidradenitis suppurativa (HS) is increasing globally. Given the potential anti-inflammatory, therapeutic, and pain management benefits of cannabis-related products, we reviewed primary literature to evaluate the prevalence and possible purpose for cannabis use among patients with HS and to provide recommendations to patients and physicians. A narrative review of original studies was conducted using Embase and Ovid Medline databases. The search strategy was confirmed by a librarian and conducted on September 1, 2023, using a detailed list of subject headings and keywords tailored to cannabis, cannabis-related products, HS, and both adult and pediatric populations. Among 43 identified studies, 6 met the eligibility criteria and encompassed 34,435 patients. Patients were mostly female, and studies were conducted across the United States, Canada, and France. Findings show higher cannabis use among HS patients, demonstrating efficacy in pain management, sleep, anxiety relief, itch relief, and improved quality of life. Cannabis may play a role in analgesia, improved quality of life, pain, itch, and overall mental health in patients with HS and healthcare providers including dermatologists should increase their familiarity in appropriate use of cannabis-related products.

Inpatient Management of Hidradenitis Suppurativa: A Delphi Consensus Study.

Inpatient hospitalization of individuals with hidradenitis suppurativa (HS) has increased. Inpatient services may not be familiar enough with this disease to understand how to manage severe HS and/or HS flares. It would be beneficial to the inpatient medical community to establish consensus recommendations on holistic inpatient care of patients with HS. A survey study was developed and distributed by Wake Forest University School of Medicine (Winston-Salem, North Carolina). A total of 26 dermatologists participated in the Delphi process, and the process was conducted in 2 rounds. Participants voted on proposal statements using a 9-point scale (1=very inappropriate; 9=very appropriate). Statements were developed using current published guidelines for management of HS and supportive care guidelines for other severe inpatient dermatologic diseases. A total of 50 statements were reviewed and voted on between the 2 rounds. Consensus was determined using the RAND/UCLA Appropriateness Method. Twenty-six dermatologists completed the first-round survey, and 24 completed the second-round survey. The 40 consensus recommendations generated through these surveys can serve as a resource for providers caring for inpatients with HS.

Interleukin 1 Receptor-Associated Kinase 4 is Overexpressed in Hidradenitis Suppurativa Skin and Correlates with Inflammatory Biomarkers.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting as painful dermal nodules, abscesses, and tunnels. Activation of the IL-1R/toll-like receptor (TLR) pathway is strongly implicated in the pathogenesis of HS; thus, the role of a key signaling node, IL-1R-associated kinase 4 (IRAK4), was investigated in a noninterventional study (NCT04440410) that enrolled 30 patients with HS. IRAK4 expression was evaluated in blood and lesional, perilesional, and nonlesional skin biopsies. Peripheral blood mononuclear cells (PBMCs) expressed IRAK4, with significantly higher levels in monocytes (P ≤ 0.0001). Ex vivo treatment of PBMCs with KT-474, a targeted degrader of IRAK4, robustly decreased IRAK4 in all immune cell types from healthy volunteers and patients with HS. Ex vivo treatment of TLR-stimulated healthy donor monocytes with KT-474 decreased IRAK4 protein levels and inhibited inflammatory cytokine production. In HS skin samples, IRAK4 protein levels were significantly higher in lesional versus nonlesional tissue (P ≤ 0.0001), and IRAK4-positive immune infiltrate increased with greater disease severity. Multiple inflammatory mediators were upregulated in HS lesional skin, correlating with IRAK4 overexpression. These data confirm the significance of the IL-1R/TLR pathway in the pathogenesis of HS and provide support for ongoing clinical studies evaluating KT-474 in the treatment of HS.

Yao syndrome: a novel systemic autoinflammatory disease with cutaneous manifestations.

Yao syndrome (YAOS) is a novel systemic autoinflammatory disease linked to the nucleotide-binding oligomerization domain (NOD2) gene. It is characterized by periodic fevers, gastrointestinal (GI) symptoms, arthritis, and dermatitis, among other symptoms. A sparse literature exists on this disease, and little is known about its dermatological manifestations. A review of available literature was performed to characterize the cutaneous manifestations of Yao syndrome. Cutaneous manifestations were documented in 85.7% of patients, with common characteristic descriptions of erythematous patches and plaques involving the face, trunk, abdomen, and extremities. Based on our review of treatment modalities employed for Yao syndrome, prednisone is an appropriate initial approach, with oral sulfasalazine and other disease-modifying antirheumatic drugs serving as appropriate secondary options. YAOS should be considered in the differential diagnosis of patients presenting with a dermatitic rash, especially in the context of concurrent articular symptoms, periodic fever, and GI symptoms.

Clinical Characteristics and Inciting Agents for Pseudoporphyria: The Mayo Clinic Experience, 1996-2020.

GENERAL PURPOSE: To raise awareness regarding the clinical presentations of patients with pseudoporphyria. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Describe the clinical presentation of pseudoporphyria.2. Identify the differential diagnoses of blistering lesions on hands and feet.3. Outline the management options for patients with porphyria.

Pseudoporphyria is an uncommon immunobullous disease that is clinically and histopathologically similar to porphyria cutanea tarda but without abnormal porphyrin levels. Limited case reports and case series of pseudoporphyria have been published. To describe the clinical characteristics and inciting agents for patients with pseudoporphyria. Health records were retrospectively reviewed for patients treated at an integrated multiregional health system from 1996 through 2020. To report results, the authors used descriptive statistics, median (range) for continuous variables, and number (percentage) for categorical data. In total, 23 patients met the inclusion criteria: 13 men and 10 women. The most common medications causing pseudoporphyria were nonsteroidal anti-inflammatory drugs, the antihypertensive agent hydrochlorothiazide, and retinoids. All patients had blisters and reported photosensitivity. Seven patients (30.4%) also had scarring, and one (4.3%) had milia. All patients had normal porphyrin levels in their serum, urine, and stool. Among patients with remission, symptoms resolved at a median of 2.5 months (range, 1 week to 24 months) after discontinuation of the suspected inciting medication. Four patients, however, had persistent symptoms at a median of 6 months (range, 2­9 months). Because pseudoporphyria is a diagnosis of exclusion, clinicians should familiarize themselves with the presentation and management of this uncommon condition.

Monoclonal gammopathy in the setting of Pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by ulcerative painful lesions with violaceous undermined borders. Up to 75% of PG cases develop in association with an underlying systemic disease. Monoclonal gammopathy is reportedly a concomitant condition with PG, with studies indicating immunoglobulin (Ig) A gammopathy as the most common. Whether gammopathy is associated with PG or is an incidental finding has been debated. We sought to investigate the association and characteristics of gammopathy in patients with PG. We retrospectively identified PG patients at our institution from 2010 to 2022 who were screened for plasma cell dyscrasia. Of 106 patients identified, 29 (27%) had a gammopathy; subtypes included IgA (41%), IgG (28%), and biclonal (IgA and IgG) (14%). Mean age was similar between those with and without gammopathy (60.7 vs. 55.9 years; P = .26). In addition, hematologic or solid organ cancer developed in significantly more patients with vs. without gammopathy (8/29 [28%] vs. 5/77 [6%]; P = .003). Among the subtypes of gammopathy, IgG monoclonal gammopathy had the highest proportion of patients with subsequent cancer development (4 of 8 patients, 50%). Study limitations include a retrospective, single-institution design with a limited number of patients. Overall, our data show a high prevalence of gammopathy in patients with PG; those patients additionally had an increased incidence of cancer, especially hematologic cancer.

Approach to the Atypical Wound.

The heterogeneity of atypical wounds can present diagnostic and therapeutic challenges; however, as the prevalence of atypical wounds grows worldwide, prompt and accurate management is increasingly an essential skill for dermatologists. Addressing the underlying cause of an atypical wound is critical for successful outcomes. An integrated approach with a focus on pain management and patient engagement is recommended to facilitate enduring wound closure. Advances in treatment, in addition to further research and clinical training, are necessary to address the expanding burden of atypical wounds.

Lower Extremity Angiosarcoma: A Life-Threatening Complication of Lymphedema.

ABSTRACT: When angiosarcoma, a rare and aggressive tumor of the soft tissue, develops in the setting of chronic lymphedema, it is referred to as Stewart-Treves syndrome. It is usually seen in chronic lymphedema of the upper limbs postmastectomy. Angiosarcoma developing in the lower limb in the setting of chronic lymphedema is rare and has a poor outcome. The presentation of angiosarcoma can vary, ranging from a bleeding papule to a plaque or a subcutaneous mass, which can later progress to ulceration or necrosis. Treatment for Stewart-Treves syndrome is aggressive because of its poor prognosis and usually requires a multidisciplinary approach of surgery, radiation, and chemotherapy. Several theories have been put forth to explain the mechanism of Stewart-Treves syndrome, but it remains ambiguous. The current literature regarding angiosarcoma developing in the setting of chronic lymphedema in the lower limb is limited to single case reports. Herein, the authors report a series of six cases of biopsy-proven angiosarcoma in the setting of lower extremity lymphedema. Providers should include angiosarcoma in the differential diagnosis of ulcerative or vascular tumors arising in the context of lower extremity lymphedema.

Proof-of-concept study exploring the effect of spesolimab in patients with moderate-to-severe hidradenitis suppurativa: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a considerable disease burden. Existing treatment options are limited and often suboptimal; a high unmet need exists for effective targeted therapies. OBJECTIVE: To explore the effects of spesolimab treatment in patients with HS. METHODS: This randomized, double-blind, placebo-controlled, proof-of-clinical-concept study was conducted at 25 centers across 12 countries from May 3, 2021, to April 21, 2022. Patients had moderate-to-severe HS for ≥1 year before enrollment. Patients were randomized (2:1) to receive a loading dose of 3600 mg intravenous spesolimab (1200 mg at Weeks 0, 1, and 2) or matching placebo, followed by maintenance with either 1200 mg subcutaneous spesolimab every 2 weeks from Week 4-10 or matching placebo. The primary endpoint was the percentage change from baseline in total abscess and inflammatory nodule (AN) count at Week 12. Secondary endpoints were the absolute change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4), percentage change from baseline in draining tunnel (dT) count, the proportion of patients achieving a dT count of zero, absolute change from baseline in revised Hidradenitis Suppurativa Area and Severity Index (HASI-R), the proportion of patients achieving Hidradenitis Suppurativa Clinical Response (HiSCR50), the proportion of patients with ≥1 flare (all at Week 12), and patient-reported outcomes (PROs). RESULTS: In this completed trial, randomized patients (N=52) received spesolimab (n=35) or placebo (n=17). The difference (95% confidence interval) versus placebo in least squares mean are reported. At Week 12, the percentage change in total AN count was similar between treatment arms: -4.1% (-31.7, 23.4). There was greater numerical improvement in the spesolimab arm, as measured by IHS4: -13.9 (-25.6, -2.3); percentage change from baseline in dT count: -96.6% (-154.5, -38.8); and the proportion of patients achieving a dT count of zero: 18.3% (-7.9, 37.5). Spesolimab treatment also improved HASI-R and HiSCR50 versus placebo. Spesolimab demonstrated a favorable safety profile, similar to that observed in trials in other diseases. CONCLUSIONS: This exploratory proof-of-clinical-concept study supports the development of spesolimab as a new therapeutic option in HS. ClinicalTrials.gov identifier: NCT04762277.

Discrepancies in hidradenitis suppurativa lesion characterization by providers and patients.

BACKGROUND: The hidradenitis suppurativa (HS) clinical response (HiSCR) has come under scrutiny as several HS clinical trials failed to meet primary endpoints with high placebo responses. This may be due to limitations of the tool and raters' ability to accurately characterize and count lesions, rather than lack of efficacy of the studied drug. Due to HS lesion complexity and potential differences in rater training, it was hypothesized that there would be discrepancies in how providers characterize and count lesions for HS clinical trials. OBJECTIVE: To evaluate how HS providers and patients name and count HS lesions and to identify discrepancies among providers to initiate the development of consensus-driven guidance for HS rater training. METHODS: An online survey was distributed to the members of HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC). Respondents were asked to classify lesion images composed of multiple and different morphology types and answer questions regarding inclusion of associated dermatological conditions. RESULTS: Forty-seven HISTORIC members responded (29 providers; 18 patients). There was variability in how respondents classified HS lesions. Of 12 questions containing images, four had ≥50% of respondents choosing the same answer. With an image of a lesion composed of different morphologies, 45% of providers counted it as a single lesion and 45% counted it as multiple distinct lesions. With an image of multiple interconnected draining tunnels, 7% of providers classified it as a single draining tunnel while 79% categorized it as multiple draining tunnels with the number estimated by visual inspection. There was also variability in deciding whether lesions occurring in associated conditions should be considered separately or included in HS lesion counts. Patient responses were also variable. CONCLUSIONS: The result of the current study reaffirms the gap in how providers characterize and count HS lesions for clinical trials and the need to develop consensus-driven rater training related to HS outcome measures.

Inflammatory and vaso-occlusive ulcers: Part I - clinical presentation and diagnosis.

In this CME, we review two specific categories of ulcers: inflammatory (where inflammation is the primary pathologic process leading to ulceration) and vaso-occlusive (where occlusion is the primary process). Inflammatory ulcers include pyoderma gangrenosum and vasculitides, whereas livedoid vasculopathy, calciphylaxis and Martorell ulcers are vaso-occlusive ulcers. Determining the causes of ulcers in these conditions may require laboratory evaluation, biopsy and imaging.

Inflammatory and vaso-occlusive ulcers: Part II - Management.

In the second part of this CME, we present an approach for the management of inflammatory and vaso-occlusive ulcers and highlight the need for further research in this field. The three overarching principles for management are etiology-specific treatment, ulcer care, and consideration of patient comorbidities and risk factors for poor healing. Both etiology-specific treatment and management of patient comorbidities and risk factors often require collaboration with providers from other specialties. Ulcer care is governed by TIME, or tissue debridement, infection control, management of moisture imbalance and epithelial edge advancement. As wound healing is a dynamic process, management should be adapted to changes in the status of the ulcer.

The Global Hidradenitis Suppurativa Atlas Methodology: Combining Global Proportions in a Pooled Analysis.

INTRODUCTION: Data concerning the global burden of hidradenitis suppurativa (HS) are limited. Reported prevalence estimates vary between 0.0003% and 4.1%, and data from various geographical regions are still to be collected. Previously reported prevalences have been limited by the methodological approach and source of data. This has resulted in great heterogeneity as prevalence data from physician-diagnosed cases poorly match those of self-reported apparent HS disease. METHODS: The Global Hidradenitis Suppurativa Atlas (GHiSA) introduces an innovative approach to determine the global prevalence of HS. This approach involves using a previously validated questionnaire to screen apparently healthy adults accompanying a patient to a non-dermatological outpatient clinic visit in a hospital or a private/family medicine clinic. The screening questionnaire (i.e., the index test) is combined with a subsequent physician-based in-person validation (i.e., the reference standard) of the participants who screen positive. Approximately ten percent of the screen-negative participants are also clinically assessed to verify the diagnostic precision of the test. The local prevalence (pi) will be estimated from each country that submits the number of patients who are HS positive according to the index test and clinical examination (n), and the corresponding total number of observations (N). CONCLUSION: The GHiSA Global Prevalence studies are currently running simultaneously in 58 countries across six continents (Africa, Europe, Australia, North America, South America, and Asia). The goal of the combined global proportion is the generation of a single summary (i.e., proportional meta-analysis), which will be done after a logit transformation and synthesized using a random-effects model. The novel standardization of the Global Prevalence Studies conducted through GHiSA enables direct international comparisons, which were previously not possible due to substantial heterogeneity in past HS prevalence studies.

Wound Bed Preparation 2024: Delphi Consensus on Foot Ulcer Management in Resource-Limited Settings.

GENERAL PURPOSE: To review a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Summarize issues related to wound assessment.2. Identify a class of drugs for the treatment of type II diabetes mellitus that has been shown to improve glycemia, nephroprotection, and cardiovascular outcomes.3. Synthesize strategies for wound management, including treatment in resource-limited settings.4. Specify the target time for edge advancement in chronic, healable wounds.

Chronic wound management in low-resource settings deserves special attention. Rural or underresourced settings (ie, those with limited basic needs/healthcare supplies and inconsistent availability of interprofessional team members) may not have the capacity to apply or duplicate best practices from urban or abundantly-resourced settings. The authors linked world expertise to develop a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. A group of 41 wound experts from 15 countries reached a consensus on wound bed preparation in resource-limited settings. Each statement of 10 key concepts (32 substatements) reached more than 88% consensus. The consensus statements and rationales can guide clinical practice and research for practitioners in low-resource settings. These concepts should prompt ongoing innovation to improve patient outcomes and healthcare system efficiency for all persons with foot ulcers, especially persons with diabetes.