Crusted Scabies in Bullous Pemphigoid Treated with Dupilumab, Systemic Steroids, and Methotrexate: A Case Report

Crusted Scabies in Bullous Pemphigoid Treated with Dupilumab, Systemic Steroids, and Methotrexate: A Case Report | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 18 March 2025 V1 Latest version Share on Crusted Scabies in Bullous Pemphigoid Treated with Dupilumab, Systemic Steroids, and Methotrexate: A Case Report Authors : Yurui Han 0009-0007-3264-8468 , Xianzhong Zhu , Yiran Qiu , Yanghai Wei , Maoyun Wei , Yujie Shi , Wenlin Yang , and Qing Qi [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174227595.50481131/v1 388 views 140 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Crusted scabies, a severe form of Sarcoptes scabiei infestation, is increasingly reported in immunocompromised individuals. We present a case of a 77-year-old male with bullous pemphigoid (BP) who developed crusted scabies during treatment with dupilumab, systemic corticosteroids (methylprednisolone 60 mg/day), and methotrexate (15 mg/week). Clinical improvement of crusted scabies was observed after topical 20% sulfur ointment application. However, mite clearance was confirmed via follow-up at one month. We reviewed cases of scabies associated with biologics and emphasize the compounded immunosuppressive risks of corticosteroids, methotrexate, and biologics. Clinicians should maintain high vigilance for parasitic infections in patients on multidrug immunosuppressive regimens. Article type: Brief Reports Title: Crusted Scabies in Bullous Pemphigoid Treated with Dupilumab, Systemic Steroids, and Methotrexate: A Case Report Yurui Han 1# , Xianzhong Zhu 12# , Yiran Qiu 1 , Yanghai Wei 1 , Maoyun Wei 1 , Yujie Shi 1 , Wenlin Yang 1 , Qing Qi 12 1 Department of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China 2 Allergy Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China #Yurui Han, Xianzhong Zhu contributed equally to this study. Correspondence authors:Qing Qi, MD Department of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, R. P. China No.250 Changgang Dong Road, Haizhu District, Guangzhou Email: [email protected] Funding sources: Supported by National Natural Science Foundation of China (Project number: 82374443). Conflict of Interest Disclosures: The authors declare no conflicts of interest. Ethical Approval: This study adhered to the Declaration of Helsinki. No approval was required. Informed consent was obtained from the patient in the study. ABSTRACT Crusted scabies, a severe form of Sarcoptes scabiei infestation, is increasingly reported in immunocompromised individuals. We present a case of a 77-year-old male with bullous pemphigoid (BP) who developed crusted scabies during treatment with dupilumab, systemic corticosteroids (methylprednisolone 60 mg/day), and methotrexate (15 mg/week). Clinical improvement of crusted scabies was observed after topical 20% sulfur ointment application. However, mite clearance was confirmed via follow-up at one month. We reviewed cases of scabies associated with biologics and emphasize the compounded immunosuppressive risks of corticosteroids, methotrexate, and biologics. Clinicians should maintain high vigilance for parasitic infections in patients on multidrug immunosuppressive regimens. Keywords: Crusted Scabies; Dupilumab; Bullous Pemphigoid; Biological Agents; Immunosuppression. Crusted scabies, is increasingly reported in immunocompromised individuals 1 . Recently, there had been successive reports of crusted scabies infections occurring in patients treated with biological agents. Here, we report a case of crusted scabies in a patient with bullous pemphigoid undergoing dupilumab, corticosteroids and methotrexate treatment. CASE REPORT A 77-year-old male presented with generalized erythema and bullous lesions, confirmed as BP via biopsy and direct immunofluorescence. No prior history of scabies was documented. Initial treatment included methylprednisolone (60 mg/d), methotrexate (15 mg/week), and dupilumab (600 mg initial dose followed by 300 mg subcutaneous injections every two weeks). BP lesions improved significantly within four weeks. One month after initiating therapy, the patient developed widespread erythema and hyperkeratotic plaques, predominantly on the limbs and trunk (Figures 1A-1C). Sarcoptic mites and eggs were identified via skin scrapings and confirmed through dermoscopy and histopathological examination (Figure 2). The diagnosis of crusted scabies was established. Due to the limited access to ivermectin, off-label 20% sulfur ointment was applied daily for seven days. Dupilumab and methotrexate were discontinued. Clinical improvement was noted within one week (Figures 3A–3B), but follow-up the scales disappeared at a one-month follow-up (Figures 3C–3D). DISCUSSION A review of the literature identified 14 cases of scabies associated with biological agents, primarily among patients with dermatologic and rheumatic conditions (Table 1). Among these patients, females comprised the majority (8/14), with a median age of 51.5 years (ranging from 17 to 80 years), 85.7% cases (12/14) were diagnosed with crusted scabies, suggesting a potential link between biological therapy and impaired antiparasitic immunity. Here, two cases treated with dupilumab 2 and one case receiving omalizumab 3 were reported. Noteworthily, all three cases were diagnosed as crusted scabies. Multiple studies suggest that crusted scabies arises from Th1/Th2-cell imbalance, with a cytotoxic T-cell type 2 response in the skin, high levels of antibody in the blood, and uncontrolled growth of the parasite 4, 5 . Dupilumab, a dual receptor antagonist of IL-4Rα, simultaneously blocks IL-4 and IL-13, which were key cytokines involved in the expulsion of parasites by enhancing intestinal mucus production and inducing eosinophilic inflammation in the intestinal mucosa 6 . Previous study had proposed the suppression of IL-4 and IL-13 signaling may increase the susceptibility and severity of parasitic infections 7 . Hence, dupilumab therapy along with skin barrier impairment and immune compromised of methylprednisolone and methotrexate may be important risk factors for our case of crusted scabies. Omalizumab specifically depletes IgE, which plays a role in protective immunity against parasites 8 . Anti-TNF-α biological agents such as adalimumab, etanercept, and infliximab may alter the immune system’s ability to control scabies infestations 9 . B cell-related monoclonal antibodies like rituximab and belimumab may affect B cell function, potentially compromising immunity 10 . The use of tocilizumab 11 , targeting the IL-6 receptor, nivolumab 12 , a PD-1 inhibitor, and risankizumab 13 , targeting IL-23, has also been reported in cases of crusted scabies. This case underscores the necessity for clinicians to remain vigilant for scabies in patients receiving biological agents and immunosuppression. Prompt recognition and management, including discontinuing the offending agent and initiating effective antiparasitic therapy, are crucial to prevent severe complications 14 . In conclusion, This case suggest that the concurrent use of corticosteroids, methotrexate, and dupilumab likely synergistically impaired antiparasitic immunity, thereby increasing the risk of crusted scabies. It emphasizes the need for heightened awareness and proactive management strategies to address this potential adverse effect. References [1] Mauro A, Colonna C, Taranto S, et al. The hidden scabies: a rare case of atypical Norwegian scabies, case report and literature review. Ital J Pediatr. 2024; 50(1): 7. [2] Rodriguez-Lago L, Borrego L. Norwegian Scabies in an Atopic Patient Under Dupilumab Treatment. Dermatitis. 2022; 33: e54–5. [3] Karson C, Mannem S, Morin L, et al. Crusted Scabies Infection in the Setting of Chronic Steroid and Omalizumab Use. Cureus. 2021; 13(7): e16490. [4] Bhat SA, Walton SF, Ventura T, et al. Early immune suppression leads to uncontrolled mite proliferation and potent host inflammatory responses in a porcine model of crusted versus ordinary scabies. PLoS Negl Trop Dis 2020; 14: e0008601. [5] Walton SF, Beroukas D, Roberts-Thomson P, et al. New insights into disease pathogenesis in crusted (Norwegian) scabies: the skin immune response in crusted scabies. Br J Dermatol. 2008; 158: 1247–55. [6] Oeser K, Schwartz C, Voehringer D. Conditional IL-4/IL-13-deficient mice reveal a critical role of innate immune cells for protective immunity against gastrointestinal helminths. Mucosal Immunol. 2015; 8(3): 672-82. [7] Braddock M, Hanania NA, Sharafkhaneh A, et al. Potential Risks Related to Modulating Interleukin-13 and Interleukin-4 Signalling: A Systematic Review. Drug Saf. 2018; 41: 489–509. [8] Cooper PJ, Ayre G, Martin C, et al. Geohelminth infections: a review of the role of IgE and assessment of potential risks of anti-IgE treatment. Allergy. 2008; 63: 409–17. [9] Morsy TA, el Alfy MS, Arafa MA, et al. Serum levels of tumour necrosis factor alpha (TNF-alpha) versus immunoglobulins (IgG, IgM, and IgE) in Egyptian scabietic children. J Egypt Soc Parasitol. 1995; 25: 773–86. [10] Androsov G, Adalsteinsson JA, Whitaker-Worth D. Letter in reply: Crusted scabies mimicking a lupus flare after rituximab and belimumab. JAAD Case Rep. 2021; 16: 28–9. [11] Baccouche K, Sellam J, Guegan S, et al. Crusted Norwegian scabies, an opportunistic infection, with tocilizumab in rheumatoid arthritis. Joint Bone Spine. 2011; 78: 402–4. [12] Adris T, McEwen MW, Jones E. Crusted scabies masquerading as a drug eruption related to nivolumab. Dermatol Online J. 2021; 27. [13] Senterre Y, Jouret G, Collins P, et al. Risankizumab-aggravated crusted scabies in a patient with Down syndrome. Dermatol Ther (Heidelb). 2020; 10: 829–34. [14] Salavastru CM, Chosidow O, Boffa MJ, et al. European guideline for the management of scabies. J Eur Acad Dermatol Venereol. 2017; 31: 1248–53. FIGURE LEGENDS Fig. 1: Hyperkeratotic plaque can be seen on the limbs and trunk(A-C). Fig. 2: Scrapings from the interdigital spaces, limbs, groin, axillae, and scrotum examined under immunofluorescence microscopy revealed adult scabies mites (A, black arrow) and eggs (A, red arrows). Dermoscopy shows white sarcoptic burrows, mite eggs and secretions (B, black arrow) X 20. Histopathological examination revealed the scabies mites (C, black arrows). Haematoxylin and eosin, original magnification. Fig. 3: The plaque were decreased after one week of treatment (A-B), and the scales disappeared at a one-month follow-up (C-D). Author/ Year Age/ Gender biological agents Comorbidities Previous treatments Types of Scabies Treatment Outcome Rodriguez et al,10.1097/DER.0000000000000926 M/ 23 Dupilumab AD Unknown crusted scabies Oral ivermectin, topical permethrin 5% cream and 5% salicylic acid resolved Karson et al,10.7759/cureus.16490 M/ 69 Omalizumab Anxiety, Depression, CIU Corticosteroids crusted scabies Oral ivermectin, topical permethrin 5% cream scabies resolved but died ( bacterial sepsis） Our case M/ 77 Dupilumab BP Corticosteroids, Methotrexate crusted scabies Topical treatment (20% sulfur ointment) Resolved Belvisi et al,10.1017/ice.2015.188 F/ 65 Adalimumab PsA Unknown crusted scabies Repeated permethrin 5% cream topical administration Large outbreak Boureau et al,10.1016/j.jbspin.2013.06.009 M/ 50 Adalimumab AS None scabies Repeated use of ivermectin, local benzyl benzoate applications, disinfection of clothes Recurred 3 months after adalimumab was resumed. Boureau et al,10.1016/j.jbspin.2013.06.009 F/20 Etanercept. AS non-steroidal anti- inflammatory drugs and methotrexate scabies Oral ivermectin, disinfection of the clothes Resolved Saillard et al,10.1016/j.jaad.2012.09.049 M/ 42 Etanercept Severe plaque psoriasis None crusted scabies Oral ivermectin，keratolytic therapy, 10% benzyl benzoate lotion Resolved Pipitone et al, 10.1016/j.jaad.2004.12.039 F/17 Infliximab Juvenile rheumatoid arthritis Rofecoxib crusted scabies Repeated permethrin cream, 5% urea cream. The patient did not clear all the crusted lesions for months Ashrafzadeh et al,10.1016/j.jdcr.2020.06.001 F/57 Rituximab PV Corticosteroids, azathioprine, and mycophenolate crusted scabies Oral ivermectin， 5% permethrin cream Resolved Androsov eh et al,10.1016/j.jdcr.2021.07.041 F/28 Rituximab and Belimumab SLE， Concurrent Sjogren syndrome Hydroxychloroquine, Corticosteroids crusted scabies oral ivermectin, 5% permethrin cream Resolved Dahuron et al,10.1016/j.revmed.2019.10.315 F/ 53 Belimumab SLE Corticosteroids, Hydroxychloroquine, Cyclophosphamide, Motecophenolate, Azathioprine crusted scabies oral ivermectin, 5% permethrin cream, antihistamines Resolved Baccouche et al, 10.1016/j.jbspin.2011.02.008 F/ 80 Tocilizumab RA Methotrexate, Corticosteroid crusted scabies repeated use of ivermectin, topical piperonyl butoxide cream Outbreak of scabies among the staff (one doctor and one nurse) Adris, et al，10.5070/D3271156097 M/ 64 Nivolumab MM Unknown crusted scabies Oral ivermectin， topical permethrin cream Resolved Senterre et al,10.1007/s13555-020-00386-8 F/ 26 Risankizumab Ps，DS Topical dermocorticosteroids, UVB-phototherapy, acitretin crusted scabies Oral ivermectin, topical permethrin 5% cream，local keratolytic care (urea cream 15%） Resolved AS, ankylosing spondylitis; PV，Pemphigus vulgaris；RA, rheumatoid arthritis; Ps, psoriasis; Psa, Psoriatic arthrit; SLE, Systemic lupus erythematosus; BP, Bullous pemphigoid; AD, Atopic dermatitis; CIU, chronic idiopathic urticaria; DS, Down syndrome; MM, Metastatic melanoma; M, male; F, female; Information & Authors Information Version history V1 Version 1 18 March 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords disease immunisation parasite skin inflammation tools and techniques Authors Affiliations Yurui Han 0009-0007-3264-8468 Guangzhou Medical University Second Affiliated Hospital View all articles by this author Xianzhong Zhu Guangzhou Medical University Second Affiliated Hospital View all articles by this author Yiran Qiu Guangzhou Medical University Second Affiliated Hospital View all articles by this author Yanghai Wei Guangzhou Medical University Second Affiliated Hospital View all articles by this author Maoyun Wei Guangzhou Medical University Second Affiliated Hospital View all articles by this author Yujie Shi Guangzhou Medical University Second Affiliated Hospital View all articles by this author Wenlin Yang Guangzhou Medical University Second Affiliated Hospital View all articles by this author Qing Qi [email protected] Guangzhou Medical University Second Affiliated Hospital View all articles by this author Metrics & Citations Metrics Article Usage 388 views 140 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Yurui Han, Xianzhong Zhu, Yiran Qiu, et al. 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