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American Journal of Clinical Dermatology May 2021Erythema nodosum is the most common form of panniculitis and is characterized by tender erythematous nodules mainly in the lower limbs on the pretibial area. The exact... (Review)
Review
Erythema nodosum is the most common form of panniculitis and is characterized by tender erythematous nodules mainly in the lower limbs on the pretibial area. The exact cause of erythema nodosum is unknown, although it appears to be a hypersensitivity response to a variety of antigenic stimuli. Although the etiology is mostly idiopathic, ruling out an underlying disease is imperative before diagnosing primary erythema nodosum. Erythema nodosum can be the first sign of a systemic disease that is triggered by a large group of processes, such as infections, inflammatory diseases, neoplasia, and/or drugs. The most common identifiable causes are streptococcal infections, primary tuberculosis, sarcoidosis, Behçet disease, inflammatory bowel disease, drugs, and pregnancy. We propose a diagnostic algorithm to optimize the initial work-up, hence initiating prompt and accurate management of the underlying disease. The algorithm includes an initial assessment of core symptoms, diagnostic work-up, differential diagnosis, and recommended therapies. Several treatment options for the erythema nodosum lesions have been previously reported; nevertheless, these options treat the symptoms, but not the triggering cause. Making an accurate diagnosis will allow the physician to treat the underlying cause and determine an optimal therapeutic strategy.
Topics: Anti-Inflammatory Agents; Diagnosis, Differential; Drug Therapy, Combination; Erythema Nodosum; Humans; Incidence; Skin; Treatment Outcome
PubMed: 33683567
DOI: 10.1007/s40257-021-00592-w -
American Journal of Clinical Dermatology May 2022Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is an inflammatory, non-infectious skin reaction characterized clinically by tender, erythematous... (Review)
Review
Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is an inflammatory, non-infectious skin reaction characterized clinically by tender, erythematous papules/plaques/pustules/nodules commonly appearing on the upper limbs, trunk, and head and neck; histologically, SS is characterized by dense neutrophilic infiltrate in the dermis. SS is accompanied by fever; an elevation of inflammatory markers (e.g., erythrocyte sedimentation rate, C reactive protein) in serum may also be observed. Although most cases of SS are idiopathic, SS also occurs in the setting of malignancy or following administration of an associated drug. SS has also been reported in association with pregnancy and a burgeoning list of infectious (most commonly upper respiratory tract infections) and inflammatory diseases; likewise, the litany of possible iatrogenic triggers has also grown. Over the past several years, a wider spectrum of SS presentation has been realized, with several reports highlighting novel clinical and histological variants. Corticosteroids continue to be efficacious first-line therapy for the majority of patients with SS, although novel steroid-sparing agents have been recently added to the therapeutic armamentarium against refractory SS. New mechanisms of SS induction have also been recognized, although the precise etiology of SS still remains elusive. Here, we catalogue the various clinical and histological presentations of SS, summarize recently reported disease associations and iatrogenic triggers, and review treatment options. We also attempt to frame the findings of this review in the context of established and emerging paradigms of SS pathogenesis.
Topics: Adrenal Cortex Hormones; Humans; Iatrogenic Disease; Neck; Skin; Sweet Syndrome
PubMed: 35157247
DOI: 10.1007/s40257-022-00673-4 -
The Chinese Journal of Physiology 2021Hidradenitis suppurativa is a cutaneous chronic inflammatory disease that is estimated to affect about 1% of the population and caused pain, malodorous discharge,... (Review)
Review
Hidradenitis suppurativa is a cutaneous chronic inflammatory disease that is estimated to affect about 1% of the population and caused pain, malodorous discharge, disfigurement, and poor quality of life with psychosocial problems. The typical features are recurrent painful nodules, abscesses, and sinus tracts on the axillae, groins, gluteal areas, and anogenital regions since postpuberty. Smoking and obesity are two major triggering factors of hidradenitis suppurativa. Women are prone to have hidradenitis suppurativa than men in Western countries, but the male-to-female ratio is reversed in oriental countries. The disease severity can be affected by menstruation, pregnancy, and menopause. Furthermore, the phenotypes are different among men and women with hidradenitis suppurativa. Men are prone to have buttock involvement while women are prone to have axillary, groins, and submammary lesions. This review introduces the skin appendages and pathophysiology of hidradenitis suppurativa and then focuses on the sex difference and the effects of sex hormones on hidradenitis suppurativa and current hormone-associated treatments.
Topics: Female; Gonadal Steroid Hormones; Hidradenitis Suppurativa; Humans; Inflammation; Male; Quality of Life; Skin
PubMed: 34975118
DOI: 10.4103/cjp.cjp_67_21 -
American Journal of Clinical Dermatology Mar 2022Hidradenitis suppurativa (HS) is a severe chronic relapsing inflammatory disorder of the hair follicle unit that can cause painful abscesses, nodules, tunnels, and... (Review)
Review
Hidradenitis suppurativa (HS) is a severe chronic relapsing inflammatory disorder of the hair follicle unit that can cause painful abscesses, nodules, tunnels, and tracts in intertriginous parts of the body. The disease can often result in disfigurement and adversely impact patient quality of life. The management of HS has expanded significantly over the past decade to include multiple modalities, including topical therapies, systemic therapies (non-biologics and biologics), surgical therapies, lifestyle changes, and management of comorbidities. Management can often be clinically challenging and may involve the combination of medical and surgical approaches for optimal results. The purpose of this review is to present an update on non-biologic and non-interventional modalities published in 2019-2021 in the clinical management of HS. With emerging therapies, ongoing clinical trials, and heightened awareness about HS, there is hope that new treatment options will revolutionize the management of patients suffering from HS.
Topics: Abscess; Comorbidity; Hair Follicle; Hidradenitis Suppurativa; Humans; Quality of Life
PubMed: 34990004
DOI: 10.1007/s40257-021-00667-8 -
Actas Dermo-sifiliograficas Nov 2020Juvenile xanthogranulomas (JXGs) are rare, benign lesions that belong to the large group of non-Langerhans cell histiocytoses. JXG presents with 1 or more erythematous... (Review)
Review
Juvenile xanthogranulomas (JXGs) are rare, benign lesions that belong to the large group of non-Langerhans cell histiocytoses. JXG presents with 1 or more erythematous or yellowish nodules that are usually located on the head or neck. Most JXG lesions are congenital or appear during the first year of life. Extracutaneous involvement is rare, but the literature traditionally suggests investigating the possibility of ocular compromise. JXG is mainly a clinical diagnosis, but a skin biopsy may sometimes be needed for confirmation. JXGs on the skin are self-limiting and usually do not require treatment. This review describes the clinical and therapeutic aspects of JXG, emphasizing available evidence and the diagnosis of extracutaneous involvement.
Topics: Biopsy; Histiocytosis, Non-Langerhans-Cell; Humans; Skin; Xanthogranuloma, Juvenile
PubMed: 32721389
DOI: 10.1016/j.ad.2020.07.004 -
Cureus Nov 2023This case report focuses on a 40-year-old female with multiple subcutaneous skin nodules presenting to the clinic for worsening skin lesions associated with erythema and...
This case report focuses on a 40-year-old female with multiple subcutaneous skin nodules presenting to the clinic for worsening skin lesions associated with erythema and mild tenderness. A biopsy of the skin lesions showed non-necrotizing granulomas with multinucleated giant cells. The patient was being worked up for non-necrotizing granulomatous skin lesions and was diagnosed with subcutaneous sarcoidosis. Sarcoidosis diagnosis is based on clinical presentation, histopathological changes, and ruling out other granulomatous causes. Our patient is being treated with systemic steroids, hydroxychloroquine, methotrexate, and adalimumab. The patient is nine months into the treatment. A clinically significant reduction in the nodule size was noted. Other systemic involvement of sarcoid was ruled out. This subcutaneous skin involvement is a rare finding called the Darier-Roussy sarcoid. Usually self-resolving but extensive, deformative lesions need to be treated.
PubMed: 38152786
DOI: 10.7759/cureus.49501 -
EClinicalMedicine Mar 2023Prurigo nodularis is a chronic skin disease characterised by intensely pruritic, hyperkeratotic nodules. Vixarelimab, a human monoclonal antibody, binds to the beta...
Efficacy and safety of vixarelimab, a human monoclonal oncostatin M receptor β antibody, in moderate-to-severe prurigo nodularis: a randomised, double-blind, placebo-controlled, phase 2a study.
BACKGROUND
Prurigo nodularis is a chronic skin disease characterised by intensely pruritic, hyperkeratotic nodules. Vixarelimab, a human monoclonal antibody, binds to the beta subunit of the oncostatin M receptor, inhibiting signalling of both interleukin 31 and oncostatin M, two cytokine pathways that contribute to pruritus and nodule formation in prurigo nodularis.
METHODS
This double-blind, placebo-controlled, phase 2a trial was done at both private and academic dermatology outpatient research clinics across the United States and Canada (n = 40). Patient eligibility criteria included age 18-75 years, physician-documented diagnosis of prurigo nodularis minimum 6 months duration of prurigo nodularis, presence of at least 10 pruritic nodules approximately 0.5-2 cm in size on at least two different anatomical locations (excluding face and scalp) and involving the extremities, and presence of normal-appearing skin between nodules; atopic dermatitis as a comorbidity was exclusionary. Patients were required to have moderate-to-severe pruritus, defined as Worst Itch-Numeric Rating Scale (WI-NRS) score ≥7 at screening and LS-mean weekly WI-NRS score ≥5 for each of the 2 consecutive weeks immediately before randomisation. Participants were randomly assigned (1:1) to receive weekly subcutaneous vixarelimab 360 mg (720 mg loading dose) or placebo using stratification factors (sex and presence of atopy) and block size 4 through the IWRS system. Stratification by atopy status was based on the reported high prevalence of atopy in this population and the potential impact of atopy in the immunopathologic process in prurigo nodularis. Patients, investigators, study sponsor, and site staff were masked to study treatment. The primary efficacy endpoint was least squares (LS)-mean percent change from baseline (PCFB) at Week 8 in weekly average Worst Itch-Numeric Rating Scale (WI-NRS) score. The primary efficacy endpoint was analysed with ANCOVA including treatment as fixed effect, with baseline WI-NRS, and randomisation stratification factor as covariates. All randomised patients who had at least 1 dose of study drug or placebo were included in the Safety Analysis Set. This trial is registered at ClinicalTrials.gov, NCT03816891.
FINDINGS
Of 50 patients randomised between March 11, 2019 and January 31, 2020, 23 vixarelimab recipients and 26 placebo recipients comprised the modified intent-to-treat analysis population (baseline LS-mean [SD] WI-NRS score, 8.3 [1.05]). Outcomes at Week 8 for vixarelimab versus placebo included LS-mean PCFB in WI-NRS score, -50.6% versus -29.4% (LS-mean difference [95% CI], -21.2% [-40.82, -1.60]; p = 0.03); ≥4-point reduction in WI-NRS score, 52.2% (12/23) versus 30.8% (8/26) (p = 0.11); PN-IGA score of 0 or 1, 30.4% (7/23) versus 7.7% (2/26) (p = 0.03); LS-mean PCFB in pruritus VAS score, -54.4% versus -32.6% (p = 0.03); and LS-mean PCFB sleep loss reduction (improvement), -56.3% versus -30.0% (p = 0.02). No deaths, serious TEAEs, or TEAEs leading to dose interruption were reported. The percentage of vixarelimab recipients reporting any TEAE was 91.3% (21/23) versus 76.9% (20/26) of placebo recipients; drug-related TEAEs generally were similar between the two groups (vixarelimab, 43.5% [10/23]; placebo, 38.5% [10/26]).
INTERPRETATION
Vixarelimab demonstrated rapid reduction of pruritus and achievement of clear/almost clear skin in one-third of the patients by Week 8. Relief of itch and clearing of skin nodules represent two important potential therapeutic advances in the management of patients suffering from the debilitating disease Prurigo Nodularis.
FUNDING
Kiniksa Pharmaceuticals, Ltd.
PubMed: 36816342
DOI: 10.1016/j.eclinm.2023.101826 -
JMIR Dermatology Jan 2024Hyaluronidase (Hyal) can reverse complications of hyaluronic acid (HA) fillers, which has contributed substantially to the popularity of such procedures. Still, there... (Review)
Review
BACKGROUND
Hyaluronidase (Hyal) can reverse complications of hyaluronic acid (HA) fillers, which has contributed substantially to the popularity of such procedures. Still, there are differing opinions regarding Hyal treatment, including dosage recommendations in filler complication management.
OBJECTIVE
We aimed to address unanswered questions regarding Hyal treatment for HA filler complications, including timing and dosage, skin pretesting, properties of various Hyals and interactions with HA gels, and pitfalls of the treatment.
METHODS
PubMed and Google Scholar databases were searched from inception for articles on Hyal therapy for filler complications. Articles were evaluated regarding their contribution to the field. The extensive literature review includes international leaders' suggestions and expert panels' recommendations.
RESULTS
There are limited controlled data but increasing clinical experience with Hyal treatment. The currently used Hyals provide good results and have an acceptable safety profile. Nonemergent complications such as the Tyndall effect, noninflamed nodules, and allergic or hypersensitivity reactions should be treated with low or moderate Hyal doses. Hyal should be considered with prior or simultaneous oral antibiotic treatment in managing inflammatory nodules. Hyal may be tried for granulomas that have not responded to intralesional steroids. Emergent complications such as vascular occlusion and blindness require immediate, high-dose Hyal treatment. Regarding blindness, the injection technique, retrobulbar versus supraorbital, remains controversial. Ultrasound guidance can increase the efficacy of the above interventions.
CONCLUSIONS
Hyal is essential in aesthetic practice because it can safely treat most HA filler complications. Immediate Hyal treatment is required for emergent complications. Aesthetic practitioners should be versed in using Hyal and effective dosage protocols.
PubMed: 38231537
DOI: 10.2196/50403 -
The Journal of Allergy and Clinical... Jan 2024Prurigo nodularis (PN) is a chronic neuroimmune skin disease characterized by bilaterally distributed pruritic hyperkeratotic nodules on extremities and trunk....
BACKGROUND
Prurigo nodularis (PN) is a chronic neuroimmune skin disease characterized by bilaterally distributed pruritic hyperkeratotic nodules on extremities and trunk. Neuroimmune dysregulation and chronic scratching are believed to both induce and maintain the characteristic lesions.
OBJECTIVES
This study sought to provide a comprehensive view of the molecular pathogenesis of PN at the single-cell level to identify and outline key pathologic processes and the cell types involved. Features that distinguish PN skin from the skin of patients with atopic dermatitis were of particular interest. We further aimed to determine the impact of the IL31RA antagonist, nemolizumab, and its specificity at the single-cell level.
METHODS
Single-cell RNA-sequencing of skin from 15 healthy donors and nonlesional and lesional skin from 6 patients each with PN and atopic dermatitis, combined with spatial-sequencing using the 10x Visium platform. Integration with bulk RNA-sequencing data from patients treated with nemolizumab.
RESULTS
This study demonstrates that PN is an inflammatory skin disease characterized by both keratinocyte proliferation and activation of profibrotic responses. This study also demonstrates that the COL11A1 fibroblast subset is a major contributor to fibrosis and is predominantly found in the papillary dermis of PN skin. Activation of fibrotic responses is the main distinguishing feature between PN and atopic dermatitis skin. This study further shows the broad effect of nemolizumab on PN cell types, with a prominent effect driving COL11A1 fibroblast and keratinocyte responses toward normal.
CONCLUSIONS
This study provides a high-resolution characterization of the cell types and cellular processes activated in PN skin, establishing PN as a chronic fibrotic inflammatory skin disease. It further demonstrates the broad effect of nemolizumab on pathological processes in PN skin.
Topics: Humans; Prurigo; Dermatitis, Atopic; Skin; Chronic Disease; RNA; Pruritus
PubMed: 37506977
DOI: 10.1016/j.jaci.2023.07.005