Painful Nodules Research Articles

Transcriptome Meta-Analysis Confirms the Hidradenitis Suppurativa Pathogenic Triad: Upregulated Inflammation, Altered Epithelial Organization, and Dysregulated Metabolic Signaling.

Hidradenitis suppurativa (HS) is an inflammatory skin condition clinically characterized by recurrent painful deep-seated nodules, abscesses, and sinus tracks in areas bearing apocrine glands, such as axillae, breasts, groins, and buttocks. Despite many recent advances, the pathophysiological landscape of HS still demands further clarification. To elucidate HS pathogenesis, we performed a meta-analysis, set analysis, and a variant calling on selected RNA-Sequencing (RNA-Seq) studies on HS skin. Our findings corroborate the HS triad composed of upregulated inflammation, altered epithelial differentiation, and dysregulated metabolism signaling. Upregulation of specific genes, such as KRT6, KRT16, serpin-family genes, and SPRR3 confirms the early involvement of hair follicles and the impairment of barrier function in HS lesioned skin. In addition, our results suggest that adipokines could be regarded as biomarkers of HS and metabolic-related disorders. Finally, the RNA-Seq variant calling identified several mutations in HS patients, suggesting potential new HS-related genes associated with the sporadic form of this disease. Overall, this study provides insights into the molecular pathways involved in HS and identifies potential HS-related biomarkers.

NOT SO "HAPPY BUMP": A complication due to hyaluronic acid.

The use of hyaluronic acid (HA) as a dermal filler is considered safe. However, as new brands come to the market, reports of adverse events are becoming more and more common. To describe a particular type of adverse effect that, unlike the erythematous, indurated, and painful nodules described in the literature as "angry red bumps," is characterized by noninflammatory, stony-like nodules that appear in sites previously treated with HA. The report of four patients who presented this complication, and the occurrence of two HA syringes from the same batch that had hardened the product inside at the time of filling. The authors propose the nomenclature "happy bump" to group adverse reactions to HA that translate into noninflammatory nodules, with a stony consistency, appearing up to 4 weeks (recent) or after one month (late) in sites previously treated with AH.

34065 Lupus panniculitis with facial hemiatrophy

A 29-year-old Hispanic woman presented with a 7-year history of facial lesions and alopecic areas on the scalp. Her initial lesions were painful nodules. In addition, the left side of her face has progressively hardened and changed in its contour. Approximately a year after onset, she developed alopecia on both sides of her scalp. At the time of presentation to us, she denied fever, arthritis, chest pain, shortness of air, and fatigue. Physical examination demonstrated facial asymmetry, erythematous indurated nodules, and plaques on the left face, as well as alopecic nodules on the scalp.

35097 Characterization of B cell dynamics in hidradenitis suppurativa: Evidence for antigen-driven pathophysiology

Hidradenitis suppurativa (HS) is a high-morbidity, chronic inflammatory skin disorder that affects an estimated 1% of adults in developed countries and is disproportionately prevalent among African Americans and women. Lesions in HS primarily affect intertriginous sites and present as painful inflammatory nodules, subcutaneous abscesses, and scarring subcutaneous tunnels. Histologically, these lesions are rich in inflammatory infiltrate including T cells, neutrophils, macrophages, dendritic cells, B cells and plasma cells. While the role of B cells and their late differentiation partner, plasma cells, are unclear in HS, emerging evidence has suggested a link between these cells, disease progression, and treatment response. Here, we further characterize B cells in HS using single cell RNA-seq (scRNA-seq) and bacteriophage immunoprecipitation sequencing (PhIP-seq) to identify local and global alterations to B cell and plasma cell populations in HS. Using published bulk RNA-seq data from HS lesions and control skin, we extracted CDR3 sequences using MiXCR software. Diversity analysis demonstrated an increase in clonotypes in HS skin compared with control skin (P < .05). Further analysis of clonal populations in HS skin using D50 diversity index revealed selective clonal expansions (P < .01). To understand whether B cell axis alterations in HS were limited to the lesion, we assayed serum from 10 HS patients and 14 controls using PhIP-seq. HS patients possessed serum autoreactivity to a set of four autoantigens compared with controls, including type I collagen (P < .01 for each). Together, these studies provide evidence for local and global alteration to B cell populations in an antigen-specific manner in HS.

35154 The role of common environmental triggers in hidradenitis suppurativa patients

Background: Hidradenitis suppurativa (HS) is a chronic skin disease that has known associations with various environmental factors. Smoking, obesity, diet, mechanical stress, and sweating are triggers that have been studied to better understand the role of lifestyle modifications in disease management. Objective: To measure the association of patient reported triggers of HS with time since diagnosis, BMI, social/family support, disease severity, and body surface area involvement. Methods: The study recruited a total of 153 patients, and 67 patients completed the self-reported patient questionnaire. Environmental triggers that were studied included mechanical stress, tight clothing, food types, washing products, heat, tobacco use, and emotional stress. Results: 26% and 20% of patients with a social support system consisting <5 family members or friends said sugary foods and bakery products, respectively, worsened their HS when compared with 3.6% and 3.6% of patients with ≥ 5 family members or friends (P = .01, P = .04). Higher Hurley stage is associated with heat, emotional stress, and weight gain worsening HS. Increasing number of painful nodules seems to be associated mechanical stress, tight-fitted clothing, and emotional stress worsening HS. Limitations: The self-reported Hurley score lacks provider-reported data. The sample size was limited by the number of patient completed questionnaires. Conclusions: HS is a complex disease that is influenced by numerous lifestyle factors. The association of various social and environmental triggers in HS patients may point to the important role that lifestyle modifications can have in HS management and overall patient quality of life.

Immunomodulatory Drugs in the Treatment of Hidradenitis Suppurativa-Possibilities and Limitations.

Hidradenitis suppurativa, also known as acne inversa, is a chronic, progressive, debilitating, recurrent inflammatory skin disease characterized by the occurrence of very severe, persistent, painful nodules, abscesses, and fistulas, most commonly found in the skin folds of the axilla, groin, gluteal, and perianal areas. Treatment is rather difficult and typically requires the use of multiple modalities. Regardless of the presence of several therapeutic options, treatment often turns out to be ineffective or poorly selected concerning the clinical picture of the disease. Thus, the search for new biologics and other target treatments of hidradenitis suppurativa is ongoing. The safety and efficacy of adalimumab, still the only U.S. Food and Drug Administration approved biologic in the hidradenitis suppurativa treatment, paved the way for new drugs to be compared with it. Several more drugs with new immunological targets are currently under investigation for the treatment of acne inversa. The aim of the article was to present the current and future targets of acne inversa treatment, simultaneously providing insights into the molecular pathomechanisms of the disease.

Effectiveness and Safety of Acitretin for the Treatment of Hidradenitis Suppurativa, Predictors of Clinical Response: A Cohort Study

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicle which presents with painful nodules, abscesses, and fistulae in apocrine gland-bearing areas of the skin. Approved treatments include antibiotics and biologic drugs such as adalimumab. Despite these treatments, HS management is challenging. Acitretin is an oral retinoid used for its management as 3rd or 4th line therapy. There is little evidence regarding the effectiveness and safety of acitretin treatment for HS, and no reports have previously explored the potential clinical predictors associated with the response to the treatment. Methods: Retrospective cohort study to assess the effectiveness and safety of acitretin treatment in HS patients who failed to respond to topical therapies. Results: Sixty-two patients with moderate to severe HS were included. A significant decrease in the International HS Severity Scoring System (IHS4) score was found over time. Higher basal IHS4 score, family history of HS, follicular phenotype, and history of follicular plugging conditions were potential predictors of response. Most patients did not suffer any adverse events, and no severe side effects were observed. The main cause of discontinuation was lack of efficacy. Conclusion: Acitretin can be considered as a therapeutic option for patients with HS. The presence of follicular phenotype or a history of components of follicular occlusion syndrome is associated with better outcomes.

Transient leg nodules

A 14-year-old male presented to a pediatric dermatology clinic for painful skin-colored leg nodules (Fig 1). For the past 7 months, these nodules would transiently appear and disappear on his left lower leg while walking far distances or uphill. In the clinic, standing or bearing weight on the leg elicited the appearance of the nodules while plantar flexion of the foot and cessation of weight bearing caused the nodules to disappear (Video 1, available on www.jaad.org). The patient had previously seen other medical providers and underwent static leg ultrasound and magnetic resonance imaging (MRI) studies which revealed no abnormalities.

Hidradenitis Suppurativa: A Perspective on Genetic Factors Involved in the Disease.

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease of the pilosebaceous unit, clinically consisting of painful nodules, abscesses, and sinus tracts mostly in, but not limited to, intertriginous skin areas. HS can be defined as a complex skin disease with multifactorial etiologies, including—among others—genetic, immunologic, epigenetic, and environmental factors. Based on genetic heterogeneity and complexity, three different forms can be recognized and considered separately as sporadic, familial, and syndromic. To date, several genetic variants associated to disease susceptibility, disease-onset, and/or treatment response have been reported; some of these reside in genes encoding the gamma-secretase subunits whereas others involve autoinflammatory and/or keratinization genes. The aim of this perspective work is to provide an overview of the contribution of several genetic studies encompassing family linkage analyses, target candidate gene studies, and -omic studies in this field. In our viewpoint, we discuss the role of genetics in Hidradenitis suppurativa considering findings based on Sanger sequencing as well as the more recent Next Generation Sequencing (i.e., exome sequencing or RNA Sequencing) with the aim of better understanding the etio-pathogenesis of the disease as well as identifying novel therapeutic strategies.

NEUROENDOCRINE CARCINOMA AFFECTING THE PAROTID GLAND: CASE REPORT WITH IMMUNOHISTOCHEMICAL STUDY

Salivary gland neuroendocrine carcinoma (sgNEC) is a rare malignant neoplasm characterized by rapid tumor growth, commonly affecting older male patients and frequently observed on the parotid gland. These tumors can be classified as primary or metastatic sgNEC. A 57-year-old White woman sought medical care for facial swelling and odynophagia. On clinical examination, a painful large nodule located on the right parotid gland was noted, as well as regional lymphadenopathy. Imaginologic analysis revealed a large and irregular mass infiltrating the parotid gland. Core needle biopsy was performed, and the histopathologic analysis revealed features of poorly differentiated sgNEC. Immunohistochemistry showed strong immunopositivity for anti-synaptophysin and chromogranin. Mindbomb 1 labeling index was approximately 30%. The antineoplastic treatment consisted of chemotherapy and adjuvant radiotherapy, and there was no tumor recurrence after 36 months of follow-up. Although rare, sgNEC must be considered in differential diagnosis of parotid gland swellings. Salivary gland neuroendocrine carcinoma (sgNEC) is a rare malignant neoplasm characterized by rapid tumor growth, commonly affecting older male patients and frequently observed on the parotid gland. These tumors can be classified as primary or metastatic sgNEC. A 57-year-old White woman sought medical care for facial swelling and odynophagia. On clinical examination, a painful large nodule located on the right parotid gland was noted, as well as regional lymphadenopathy. Imaginologic analysis revealed a large and irregular mass infiltrating the parotid gland. Core needle biopsy was performed, and the histopathologic analysis revealed features of poorly differentiated sgNEC. Immunohistochemistry showed strong immunopositivity for anti-synaptophysin and chromogranin. Mindbomb 1 labeling index was approximately 30%. The antineoplastic treatment consisted of chemotherapy and adjuvant radiotherapy, and there was no tumor recurrence after 36 months of follow-up. Although rare, sgNEC must be considered in differential diagnosis of parotid gland swellings.

A RARE CASE OF A RECURRENT LEIOMYOSARCOMA OF THE BUCCAL MUCOSA

Leiomyosarcomas are rare malignant tumors that affect smooth muscle tissue. In the oral cavity, leiomyosarcomas are exceedingly rare. The diagnosis is challenging due to the overlap of morphologic findings with several spindle cell tumors. Herein, we reported a rare recurrent case of leiomyosarcoma in a 73-year-old woman presenting clinically as a painful nodule on the buccal mucosa. Microscopically, the tumor showed atypical spindle cells with elongated, blunt-ended nuclei and eosinophilic cytoplasm arranged in a fascicular pattern. Immunohistochemistry showed positivity for vimentin, α-SMA, HHF35, h-Caldesmon, and focal positivity for desmin. S-100 protein, CD34, myogenin, and pan-cytokeratin (AE1/AE3) were negative. Surgical excision followed by chemotherapy was performed. No recurrence was observed after 12 months of follow-up. Careful histopathologic analysis, supported by immunohistochemistry, is essential to ensure a correct diagnosis. Early wide surgical excision and prolonged follow-up is strongly recommended.

UNUSUAL ORAL MANIFESTATION OF PARACOCCIDIOIDOMYCOSIS MIMICKING ORAL SYPHILIS

A 38-year-old White man, rural dweller, presented to the stomatology service reporting a painful nodule with ulcerated areas in the buccal mucosa on the right side extending to the upper and lower lips about 1 year ago. He reported mouth opening limitation and difficulty eating. Facial asymmetry was also noticed in the extraoral examination. Some oral infectious diseases were considered as diagnostic hypotheses. Laboratory exams and partial biopsy were conducted. Serological tests were compatible with syphilis and microscopic features were inconclusive. Treatment with penicillin G benzathine intramuscular and dipyrone was prescribed. The patient returned 3 months later for follow-up examination without regression of signs and symptoms. A new biopsy was performed, and microscopic features confirmed oral paracoccidioidomycosis. The patient was referred to an infectologist and pneumologist. Treatment with itraconazole 100 mg was performed. Partial remission of oral lesions was observed after 2 months.

Erythema Induratum of Bazin, a Rare Manifestation of Cutaneous Tuberculosis: A Case Report

Background: Erythema induratum of Bazin is a rare manifestation of cutaneous tuberculosis. It may mimic some systemic disorders like sarcoidosis, poly arteritis nodosa, lymphoproliferative disorder, Histoplasmosis, and lupus profundus. Case Presentation: A 38-year young female, diabetic, and hypertensive presented with multiple painful skin lesion over anterior part of her leg for 3 months. These skin lesion used to appear as painful erythematous nodules of variable size and shape over the anterior and lateral aspects of both legs that became ulcerate, healed with hyperpigmentation. On examinations, all of her systemic examinations revealed unremarkable except skin lesion. Punch biopsy from skin lesion revealed lobular panniculitis with granuloma suggestive of erythema induratum and MTB gene Xpert from skin lesion found positive. Thereafter, she was put on anti TB therapy six-month regimens according to the national TB guideline, Bangladesh. After 2 and half months of treatment, her skin lesion disappeared. Conclusion: In a TB prevalent country, erythema induratum should be kept in differential diagnosis along with others. As it is usually underdiagnosed or misdiagnosed because of the absence of typical clinical features of TB, therefore comprehensive investigations like skin biopsy with histopathology, detecting DNA of Mycobacterium tuberculosis by PCR, positive Mantoux test are the cornerstone for confirmatory diagnosis. J MEDICINE 2022; 23: 165-168

803 Epidermal inflammatory activity is an important driver of hidradenitis suppurativa lesions

Hidradenitis suppurativa (HS) is an inflammatory skin disorder of the pilosebaceous unit defined by painful nodules, tunnels, and scarring. Previous studies documented dermal cell infiltrate and the abundance of inflammatory cytokines in HS lesions, including TNFα, IL-17, and IL-1β. However, not much is currently known about the contribution of keratinocytes and immune cell activity within the epidermis in HS. We found that the degree of epidermal inflammation in HS lesions positively correlated with Hurley stage of disease (r =0.746; p=0), indicating the evolution of epidermal responses with disease severity. Keratinocytes were the primary producers of TNFα (p<0.05) and IL-6 (p<0.05) in HS lesions at all Hurley stages. Increased expression of CXCL3 (5-fold; p<0.01) in keratinocytes of stage III lesions positively correlated with increased recruitment of neutrophils to stage III lesional epidermis. Compared to healthy keratinocytes, enhanced production of chemokines from HS keratinocytes, including CCL22 (stage II 4-fold; p=0.09) and CCL3 (stages II and III p<0.05; 30-fold and 10-fold respectively), was associated with CD8 T cell infiltration and corresponding chemokine receptor expression in the epidermis. These recruited immune cells strongly produce or enable the production of IFNγ (>50 fold), IL-17A (500-fold), and IL-1β (5 to 10-fold), as well as IFNβ1, CXCL10, and STAT1 (HS II/III lesions; p<0.05 for all) by multiple cell types locally in the epidermis, likely generating positive feedback for increased inflammation. As epidermal inflammation evolves during disease progression and contributes to immune cell recruitment, our data suggest that topical therapeutics that block cytokine and chemokine production from the epidermis may be efficacious in HS. In all, our results collectively indicate that keratinocytes are not simply bystanders in HS inflammatory events, but rather actively contribute to HS pathogenesis.

LB926 COVID-19 vaccine hesitancy in a cohort of hidradenitis suppurativa patients

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease manifest as painful nodules, abscesses, and draining sinus tracts (“tunnels”). Numerous studies of SARS-CoV-2 and currently available mRNA vaccines have been published in recent months, including investigations into the phenomenon of vaccine hesitancy. However, the rationality driving COVID-19 vaccine hesitancy has not yet been thoroughly explored or described in patients with HS. Methods: An IRB-retrospective chart review and telephone survey of patients receiving care at Einstein/Montefiore HS Center (MMC-HSC) were conducted between September-December 2021.

270 Impact of COVID-19 infection on hidradenitis suppurativa activity

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease manifest as painful nodules, abscesses, and draining sinus tracts (“tunnels”). Recent studies have shown increased inflammation and immune system hyperactivity are hallmarks of SARS-CoV-2 (COVID-19) infection and typically forecast disease progression. Coincidentally, chronic inflammation and immune dysregulation are characteristic of HS. We sought to examine if COVID-19 infection affected HS activity. An IRB-approved retrospective chart review and telephone survey of patients receiving care at the Einstein/Montefiore HS Center (HSC) was conducted between September-December 2021.

LB924 Ceftazidime-avibactam: A novel treatment for advanced hidradenitis suppurativa

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease manifest as painful nodules, abscesses, and draining sinus tracts (“tunnels”). While treatment consists of antibacterial, anti-hormonal, and anti-inflammatory modalities, advanced and recalcitrant HS poses a formidable challenge. We have found penem-class antibiotics are uniquely efficacious; however, flares often signal the emergence of penem-resistance requiring an alternative approach. We report dramatic regression of advanced HS with ceftazidime-avibactam.

729 Upregulation of caveolin-1 in lesional biopsies of hidradenitis suppurativa: A case series report

Hidradenitis suppurativa (HS) is an overlooked and often misdiagnosed inflammatory skin condition characterized by painful recurrent nodules and abscesses that rupture, leading to development of sinus tracts. Because of the associated pain, sensitive locations, drainage, odor and scarring, this condition has a tremendously negative psychosocial impact. Considering that 1) early stages of HS are often mistaken for other conditions, 2) pathophysiology is relatively unknown and 3) there are no established biomarkers of disease, it is unsurprising that an average delay in the correct diagnosis of HS is between 7-12 years.

Lobular Panniculitis in a Patient with Chronic Lymphoid Leukemia

Panniculitis is the inflammation of the subcutaneous fat that presents as red, painful nodules under the skin and may be a manifestation of internal disease. Causes of lobular panniculitis include systemic lupus erythema, pancreatic disorders, α1-antitrypsin deficiency, or infection. This case discusses a 63-year-old female that presents with lobular panniculitis without vasculitis associated with chronic lymphoid leukemia. Though cutaneous manifestations due to chronic lymphoid leukemia are not uncommon, it is rare to see panniculitis associated with chronic lymphoid leukemia.

BI14: Painful cutaneous nodules in chronic neutrophilic leukaemia

BI14: Painful cutaneous nodules in chronic neutrophilic leukaemia