Development of crusted scabies during biologic therapy: A systematic review

To the Editor: Crusted scabies (CS) is a rare severe form of scabies characterized by high mite burden and crusted scaling lesions that often manifest in immunocompromised patients.1Bergamin G. Hudson J. Currie B.J. Mounsey K.E. A systematic review of immunosuppressive risk factors and comorbidities associated with the development of crusted scabies.Int J Infect Dis. 2024; 143107036https://doi.org/10.1016/j.ijid.2024.107036Abstract Full Text Full Text PDF Scopus (0) Google Scholar Biologics are targeted immunomodulators and may increase the risk of developing CS. Given that CS can lead to severe consequences such as sepsis,1Bergamin G. Hudson J. Currie B.J. Mounsey K.E. A systematic review of immunosuppressive risk factors and comorbidities associated with the development of crusted scabies.Int J Infect Dis. 2024; 143107036https://doi.org/10.1016/j.ijid.2024.107036Abstract Full Text Full Text PDF Scopus (0) Google Scholar it is important for physicians to consider CS in patients undergoing immune-suppressing therapies presenting with a nonresolving rash. Therefore, this systematic review summarizes reports of CS in patients undergoing biologic therapy. An Embase and MEDLINE search was conducted on May 17, 2024, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using variations of key words for scabies and specific biologics (Supplementary Table I, available via Mendeley at https://doi.org/10.17632/wkvt9bdm2x.1). The Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence was used for assessing the quality of evidence. Janus kinase inhibitors were included in the search; however, no cases of CS were associated with Janus kinase inhibitor therapy. Of 176 identified studies by 2 independent reviewers, 10 case studies met inclusion criteria, representing 10 patients (Fig 1; Table I). The mean age was 48.7 (range 17-80) years, and 7 were female. CS developed in patients undergoing treatment with tumor necrosis factor α inhibitors (3/10), interleukin-4 receptor inhibitors (2/10), B-cell inhibitors (2/10), and finally single cases of omalizumab and tocilizumab. Concurrent immunosuppressants include systemic corticosteroids (4/10) and methotrexate (1/10).Table ICases of crusted scabies during biologic therapyStudyStudy type (level of evidence)Age (y)/sexIndication for biologicComorbiditiesBiologic classBiologic name (route, dose, and frequency)Concurrent medications (route, dose, and frequency)Latency period, monthsLocation of scabies infestationPresentationDiagnosisBiologic stoppedTreatment for crusted scabies (route, dose, and frequency)ResolutionResolution period, wks1CRS (5)28/FSLENRB-cell inhibitorBelimumab (SC, 700 mg, Q4W); rituximab (SC, 1,000 mg, Q2W)Corticosteroids (NR, NR, NR); HCQ (NR, NR, NR)4Face, hands, and scalpPruritic, hyperkeratotic erythematous rash with burrowsSkin scraping and microscopyNRIvermectin (orally or by mouth, 12 mg, 5 doses) and permethrin (TOP, 5%, every day)CRNR2CRS (5)57/FPemphigus vulgarisNRB-cell inhibitorRituximab (SC, 500 mg, Q1W)Alendronate (NR, NR, NR); corticosteroids (orally or by mouth, 20 mg, every day)NRAxilla and lower extremitiesNonpruritic, hyperkeratotic, scaly, and velvety plaquesBiopsy, skin scraping, and microscopyNIvermectin (orally or by mouth, 200 μg/kg, NR) and permethrin (TOP, 5%, NR)CR23CRS (5)80/FRAPneumoniaIL-6R inhibitorTocilizumab (SC, 8 mg/kg, Q4W)Corticosteroids (orally or by mouth, 20 mg, every day); and MTX (orally or by mouth, NR, NR)NRExtremities, scalp, and trunkPruritic, erythroderma followed by hyperkeraotitc, and crusted lesionsBiopsy, skin scraping, and microscopyYIvermectin (orally or by mouth, 9 mg, 3 doses) and piperonyl butoxide (TOP, NR, every day)CR44CRS (5)65/FPsABone fractureTNF-α inhibitorAdalimumab (SC, NR, and NR)NRNREntire bodyNonpruritic, erythematous lesionsSkin scraping and microscopyNAntibiotics (NR, NR, NR) and permethrin (TOP, 5%, NR)NRNR5CRS (5)69/MIdiopathic urticariaAnxiety; depressionanti-IgEOmalizumab (SC, NR, and NR)Corticosteroids (NR, NR, and NR)NRFeet, hands, and trunkPruritic, excoriated petechial and ecchymotic lesions with scaleBiopsyNRRituximab (NR, NR, NR); prednisone (NR, NR, NR); ivermectin (orally or by mouth, 18 mg, 5 doses); and permethrin (TOP, 5%, Q1W)PRNR6CRS (5)17/FJuvenile rheumatoid arthritisNRTNF-α inhibitorInfliximab (SC, 6 mg/kg, Q8W)Rofecoxib (NR, NR, and NR)NRExtremities and trunkNonpruritic, hyperkeratotic, and linear plaques with burrowsSkin scraping and microscopyNPermethrin (TOP, NR, NR) and urea (TOP, 5%, NR)NRNR7CRS (5)23/MAtopic dermatitisAutismIL-4R inhibitorDupilumab (SC, 300 mg, Q2W)NRNRPerimubilical and upper extremitiesNonpruritic, hyperkeratotic plaques and pruriginous vesiclesSkin scraping and microscopyYIvermectin (orally or by mouth, 14 mg, 5 doses); permethrin (TOP, 5%, every day); and salicylic acid (TOP, 5%, every day)CR38CRS (5)42/MPsoriasisAlcoholismTNF-α inhibitorEtanercept (SC, 50 mg, Q1W)NR36Extremities, scalp, and trunkMildly pruritic hyperkeratotic plaques with burrows and scaleSkin scraping and microscopyYBenzyl benzoate (TOP, 10%, every day); and ivermectin (orally or by mouth, 200 ug/kg, 2 doses)CR19CRS (5)26/FPsoriasis-like lesionsTrisomy 21IL-23 inhibitorRisankizumab (SC, NR, Q2W)NRNREntire bodyNonpruritic, hyperkeratotic, ichtyosiform plaques with fissuresBiopsyYIvermectin (orally or by mouth, 200 ug/kg, 7 doses); permethrin (TOP, 50 mg/g, every day); and urea (TOP, 15%, twice a day)CR110CRS (5)80/FUlcerative colitisAtopy, hypothyroidismIL-4R inhibitorDupilumab (SC, 300 mg, NR)NRNRExtremities, scalp, periungal, and trunkNonpruritic hyperkeratotic plaques with crust, fissures, and powdery scaleBiopsyNRIvermectin (orally or by mouth, 200 ug/kg, 2 doses); permethrin (TOP, 5%, every day)CR2CR, Complete resolution; CRS, case report; IL, interleukin; MTX, methotrexate; N, no; NR, not reported; PR, partial resolution; PsA, psoriatic arthritis; Q1W, every week; Q2W, every 8 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks; R, receptor; RA, rheumatoid arthritis; SC, subcutaneous; SLE, systemic lupus erythematosus; TNF, tumor necrosis factor; TOP, topical; Y, yes. References are included in Supplementary File 1 (available via Mendeley at https://doi.org/10.17632/wkvt9bdm2x.1). Open table in a new tab CR, Complete resolution; CRS, case report; IL, interleukin; MTX, methotrexate; N, no; NR, not reported; PR, partial resolution; PsA, psoriatic arthritis; Q1W, every week; Q2W, every 8 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks; R, receptor; RA, rheumatoid arthritis; SC, subcutaneous; SLE, systemic lupus erythematosus; TNF, tumor necrosis factor; TOP, topical; Y, yes. References are included in Supplementary File 1 (available via Mendeley at https://doi.org/10.17632/wkvt9bdm2x.1). The most common morphological manifestation was hyperkeratotic lesions (8/10). Fewer than half of patients had pruritus (4/10) and burrows (3/10). Mites were detected by skin scrapings and using microscopy (7/10) and skin biopsies (3/10). Of the 8 cases that reported improvement after treatment, all used a topical scabicide in conjunction with oral ivermectin. Topical scabicides included permethrin (6/8), benzoyl benzoate (1/8), and piperonyl butoxide (1/8). Biologics were continued in one case, stopped in half of cases (4/8), and 3 cases did not report biologic status. In this study, we describe 10 cases of CS that are associated with biologic use. Notably, we highlight that most cases were responsive to conventional treatments with topical scabicides and oral ivermectin. Our study does not establish a causal relationship. The first major limitation is the small sample size. CS is a rare phenomenon. From 1998 to 2023, only 683 cases were described; however, the 5-year publication rate reporting CS is increasing.1Bergamin G. Hudson J. Currie B.J. Mounsey K.E. A systematic review of immunosuppressive risk factors and comorbidities associated with the development of crusted scabies.Int J Infect Dis. 2024; 143107036https://doi.org/10.1016/j.ijid.2024.107036Abstract Full Text Full Text PDF Scopus (0) Google Scholar In the future, increasing the use of biologics and better reporting of CS may reveal if there is a true association. Another limitation is that half of the patients included in our study were taking concomitant immunosuppressives with unknown doses. Immunosuppressive agents are known risk factors for developing CS1Bergamin G. Hudson J. Currie B.J. Mounsey K.E. A systematic review of immunosuppressive risk factors and comorbidities associated with the development of crusted scabies.Int J Infect Dis. 2024; 143107036https://doi.org/10.1016/j.ijid.2024.107036Abstract Full Text Full Text PDF Scopus (0) Google Scholar and can be confounding factors. However, biologics alone do increase the risk of serious infections.2Penso L. Dray-Spira R. Weill A. Pina Vegas L. Zureik M. Sbidian E. Association between biologics use and risk of serious infection in patients with psoriasis.JAMA Dermatol. 2021; 157: 1056-1065https://doi.org/10.1001/jamadermatol.2021.2599Crossref Scopus (43) Google Scholar,3Singh J.A. Cameron C. Noorbaloochi S. et al.Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis.Lancet. 2015; 386: 258-265https://doi.org/10.1016/S0140-6736(14)61704-9Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar This can possibly worsen outcomes given that mortality in CS is associated with bacteremia.4Hasan T. Krause V.L. James C. Currie B.J. Crusted scabies; a 2-year prospective study from the Northern Territory of Australia.PLOS Negl Trop Dis. 2020; 14e0008994https://doi.org/10.1371/JOURNAL.PNTD.0008994Crossref Google Scholar With limitations in mind, this study highlights treatment options for CS in patients using biologics and encourages consideration of CS as a possible complication during biologic treatment. Further studies are needed to better understand the findings from our study. None disclosed.

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