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Drug-Induced Neutropenia During Treatment of Non-Neoplastic Dermatologic Diseases: A Review

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Abstract

Idiosyncratic drug-induced neutropenia (DIN) is a rare, potentially fatal adverse reaction. A literature search was performed on Pubmed and Embase, targeting articles indicating neutropenia as a complication during the treatment of non-neoplastic dermatological disorders. In 66 identified articles, the common incriminated drugs included conventional oral immunomodulators, topical cytotoxic agents, antibacterials, antifungals, biologics and targeted synthetic disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs, and retinoids, with dapsone being reported most often. The duration of drug exposure before the diagnosis of neutropenia varied, but mostly ranged from days to weeks. The majority of patients recovered after drug discontinuation and supportive management including antibiotics and granulocyte colony-stimulating factor, but fatal cases were reported. The proposed pathogenesis of DIN consists of direct drug toxicity and immune-mediated reaction. Certain genetic variants, individual variability in enzyme efficiency, and concomitant use of other drugs may increase the risk of DIN. Being familiar with the most commonly implicated agents and risk factors helps early identification and prompt management of this potentially fatal complication.

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References

  1. Revuelta-Herrero JL, García-Sánchez R, Anguita-Velasco J, de Lorenzo-Pinto A, Ortega-Navarro C, Sanjurjo-Sáez M. Drug safety surveillance within a strategy for the management of non-chemotherapy drug-induced neutropenia. Int J Clin Pharm. 2019;41:1143–7.

    CAS  PubMed  Google Scholar 

  2. Curtis BR. Non–chemotherapy drug–induced neutropenia: key points to manage the challenges. Hematology. 2017;2017:187–93.

    PubMed  Google Scholar 

  3. Andrès E, Mourot-Cottet R, Maloisel F, Séverac F, Keller O, Vogel T, et al. Idiosyncratic drug-induced neutropenia and agranulocytosis. QJM An Int J Med. 2017;110:299–305.

    Google Scholar 

  4. Andersohn F, Konzen C, Edeltraut G. Annals of internal medicine review systematic review: agranulocytosis Induced by nonchemotherapy. Ann Intern Med. 2007;146:657–66.

    PubMed  Google Scholar 

  5. Andrès E, Zimmer J, Mecili M, Weitten T, Alt M, Maloisel F. Clinical presentation and management of drug-induced agranulocytosis. Expert Rev Hematol. 2011;4:143–51.

    PubMed  Google Scholar 

  6. Stock W, Hoffman R. White blood cells 1: non-malignant disorders. Lancet. 2000;355:1351–7.

    CAS  PubMed  Google Scholar 

  7. Andrès V, Zulfiqar S, Mourot-Cottet G. State of art of idiosyncratic drug-induced neutropenia or agranulocytosis, with a focus on biotherapies. J Clin Med. 2019;8:1351.

    PubMed Central  Google Scholar 

  8. Benichou C, Solal Celigny P. Standardization of definitions and criteria for causality assessment of adverse drug reactions. Drug-induced blood cytopenias: report of an international consensus meeting. Nouv Rev Fr Hematol. 1991;33:257–62.

    CAS  PubMed  Google Scholar 

  9. Johnston A, Uetrecht J. Current understanding of the mechanisms of idiosyncratic drug-induced agranulocytosis. Expert Opin Drug Metab Toxicol. 2015;11:243–57.

    CAS  PubMed  Google Scholar 

  10. Kaufman DW, Kelly JP, Levy M, Shapiro S. The drug etiology of agranulocytosis: an update of the international agranulocytosis and aplastic anemia study. Pharmacoepidemiol Drug Saf. 1993;2:S25–9.

    Google Scholar 

  11. Hon KL, Chang M, Chong SC, Yuen YP, Tsui SKW. Adverse effects of azathioprine in a child and her mother with eczema. Indian J Pediatr. 2018;85:918–9.

    PubMed  Google Scholar 

  12. Berth-Jones J, Takwale A, Tan E, Barclay G, Agarwal S, Ahmed I, et al. Azathioprine in severe adult atopic dermatitis: a double-blind, placebo-controlled, crossover trial. Br J Dermatol. 2002;147:324–30.

    CAS  PubMed  Google Scholar 

  13. Yan W, Zhou YH, Wang L, Xiao J, Li W. NUDT15 polymorphism and severe azathioprine-induced myelosuppression in a Chinese man with pemphigus vulgaris. Br J Dermatol. 2018;178:e40–1.

    CAS  PubMed  Google Scholar 

  14. Tichy M, Urbanek J, Sternbersky J, Ditrichova D, Hercogova J. Life-threatening course of pemphigus vulgaris complicated by sepsis caused by azathioprine-induced bone marrow suppression, successfully managed with combination therapy. Dermatol Ther. 2014;27:183–6.

    PubMed  Google Scholar 

  15. Laha B, Guha R, Hazra A. Multiple cutaneous neutropenic ulcers associated with azathioprine. Indian J Pharmacol. 2012;44:646–8.

    PubMed  PubMed Central  Google Scholar 

  16. Shih YC, Zou YR, Wang B, Zheng J, Pan M. Azathioprine-induced myelosuppression in two pemphigus vulgaris patients with homozygous polymorphism of NUDT15. J Dermatol. 2019;46:e59–61.

    PubMed  Google Scholar 

  17. Patel AA, Swerlick RA, McCall CO. Azathioprine in dermatology: the past, the present, and the future. J Am Acad Dermatol. 2006;55:369–89.

    PubMed  Google Scholar 

  18. Wang T-S, Chiu H-Y, Wu LS-H, Chu C-Y, Tsai T-F. Correlation of thiopurine methyltransferase and inosine triphosphate pyrophosphatase polymorphisms and adverse effects induced by azathioprine treatment in Taiwanese dermatology patients. Dermatologica Sin. 2014;32:13–8.

    Google Scholar 

  19. Walker GJ, Harrison JW, Heap GA, Voskuil MD, Andersen V, Anderson CA, et al. Association of genetic variants in NUDT15 with thiopurine-induced myelosuppression in patients with inflammatory bowel disease. JAMA. 2019;321:773–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Roberts RL, Barclay ML. Update on thiopurine pharmacogenetics in inflammatory bowel disease. Pharmacogenomics. 2015;16:891–903.

    CAS  PubMed  Google Scholar 

  21. Lee YJ, Hwang EH, Park JH, Shin J-H, Kang B, Kim S-Y. NUDT15 variant is the most common variant associated with thiopurine-induced early leukopenia and alopecia in Korean pediatric patients with Crohn’s disease. Eur J Gastroenterol Hepatol. 2016;28:475–8.

    CAS  PubMed  Google Scholar 

  22. Rahhal RM, Bishop WP. Initial clinical experience with allopurinol-thiopurine combination therapy in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2008;14:1678–82.

    PubMed  Google Scholar 

  23. Huang P-W, Tseng Y-H, Tsai T-F. Predictive value of NUDT15 variants on neutropenia among han chinese patients with dermatologic diseases: a single-center observational study. Dermatol Ther (Heidelb). 2020;10:263–71.

    PubMed  PubMed Central  Google Scholar 

  24. Cutolo M, Sulli A, Pizzorni C, Seriolo B, Straub RH. Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis. 2001;60:729–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Shupack JL, Webster GF. Pancytopenia following low-dose oral methotrexate therapy for psoriasis. JAMA J Am Med Assoc. 1988;259:3594–6.

    CAS  Google Scholar 

  26. Primka EJ, Camisa C. Methotrexate-induced toxic epidermal necrolysis in a patient with psoriasis. J Am Acad Dermatol. 1997;36:815–8.

    PubMed  Google Scholar 

  27. Chen T-J, Chung W-H, Chen C-B, Hui RC-Y, Huang Y-H, Lu Y-T, et al. Methotrexate-induced epidermal necrosis: a case series of 24 patients. J Am Acad Dermatol. 2017;77:247.e2–255.e2.

    Google Scholar 

  28. Turck M. Successful psoriasis treatment then sudden “cytotoxicity”. Hosp Pract. 1984;19:175–6.

    CAS  Google Scholar 

  29. Al-Quteimat OM, Al-Badaineh MA. Methotrexate and trimethoprim–sulphamethoxazole: extremely serious and life-threatening combination. J Clin Pharm Ther. 2013;38:203–5.

    CAS  PubMed  Google Scholar 

  30. Dixon AJ, Wall GC. Probable colchicine-induced neutropenia not related to intentional overdose. Ann Pharmacother. 2001;35:192–5.

    CAS  PubMed  Google Scholar 

  31. Eleftheriou G, Bacis G, Fiocchi R, Sebastiano R. Colchicine-induced toxicity in a heart transplant patient with chronic renal failure. Clin Toxicol (Phila). 2008;46:827–30.

    CAS  Google Scholar 

  32. Lee K-Y, Kim DY, Chang JY, Bang D. Two cases of acute leukopenia induced by colchicine with concurrent immunosuppressants use in Behçet’s disease. Yonsei Med J. 2008;49:171–3.

    PubMed  PubMed Central  Google Scholar 

  33. Tsoi MF, Cheung TT, Lam MPS, Cheung CL, Wong ICK, Hung IFN, et al. Safety of colchicine for gout: a ten-year survey of the Hong Kong population. Clin Ther. 2017;39:e36–7.

    Google Scholar 

  34. Jick H, Myers MW, Dean AD. The risk of sulfasalazine- and mesalazine-associated blood disorders. Pharmacotherapy. 1995;15:176–81.

    CAS  PubMed  Google Scholar 

  35. McKenna KK, Burrows D. Leucopenia, thrombocytopenia and lymphadenopathy associated with sulphasalazine. Clin Exp Dermatol. 1994;19:419–20.

    CAS  PubMed  Google Scholar 

  36. Orden RA, Timble H, Saini SS. Efficacy and safety of sulfasalazine in patients with chronic idiopathic urticaria. Am Coll Allergy Asthma Immunol. 2014;112:64–70.

    CAS  Google Scholar 

  37. McGirt LY, Vasagar K, Gober LM, Saini SS, Beck LA. Successful treatment of recalcitrant chronic idiopathic urticaria with sulfasalazine. Arch Dermatol. 2006;142:1337–42.

    CAS  PubMed  Google Scholar 

  38. Wadelius M, Eriksson N, Kreutz R, Bondon-Guitton E, Ibañez L, Carvajal A, et al. Sulfasalazine-induced agranulocytosis is associated with the human leukocyte antigen locus. Clin Pharmacol Ther. 2018;103:843–53.

    CAS  PubMed  Google Scholar 

  39. Chew CY, Mar A, Nikpour M, Saracino AM. Hydroxychloroquine in dermatology: new perspectives on an old drug. Australas J Dermatol. 2020;82:72–9.

    Google Scholar 

  40. Chernof D, Taylor KS. Hydroxychloroquine-induced agranulocytosis. Arch Dermatol. 1968;97:163–4.

    CAS  PubMed  Google Scholar 

  41. Sames E, Paterson H, Li C. Hydroxychloroquine-induced agranulocytosis in a patient with long-term rheumatoid arthritis. Eur J Rheumatol. 2016;3:91–2.

    PubMed  Google Scholar 

  42. Sharma B, Manta D. 1218: hydroxychloroquine induced profound neutropenia with septic shock. Crit Care Med. 2013;41:A311–2.

    Google Scholar 

  43. Shah A, Albrecht J, Boniila-Martinez Z, Okawa J, Rose M, Rosenbach M, et al. Lenalidomide for the treatment of resistant discoid lupus erythematosus. Arch Dermatol. 2009;145:303–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Gribben JG, Fowler N, Morschhauser F. Mechanisms of action of lenalidomide in B-cell non-hodgkin lymphoma. J Clin Oncol Am Soc Clin Oncol. 2015;33:2803–11.

    CAS  Google Scholar 

  45. Cohen PR. Topical application of 5-fluorouracil 5 percent cream associated with severe neutropenia: Discussion of a case and review of systemic reactions after topical treatment with 5-fluorouracil. Dermatol Online J. 2018;24.

  46. Johnson MR, Hageboutros A, Wang K, High L, Smith JB, Diasio RB. Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. Clin Cancer Res. 1999;5:2006–11.

    CAS  PubMed  Google Scholar 

  47. Dillaha CJ, Jansen GT, Honeycutt WM, Holt GA. Further studies with topical 5-fluorouracil. Arch Dermatol. 1965;92:410–7.

    CAS  PubMed  Google Scholar 

  48. Erlanger M, Martz G, Ott F, Storck H, Rieder J, Kessler S. Cutaneous absorption and urinary excretion of 6-14C-5-fluorouracil ointment applicated in an ointment to healthy and diseased human skin. Dermatologica. 1970;140(Suppl 1):7–14.

    Google Scholar 

  49. Stoehr GP, Peterson AL. Systemic complication of local podophyllin therapy. Ann Intern Med. 1978;89:362–3.

    CAS  PubMed  Google Scholar 

  50. Ranawaka RR, Mendis S, Weerakoon HS. Dapsone-induced haemolytic anaemia, hepatitis and agranulocytosis in a leprosy patient with normal glucose-6-phosphate-dehydrogenase activity. Lepr Rev. 2008;79:436–40.

    PubMed  Google Scholar 

  51. Bhat RM, Radhakrishnan K. A case report of fatal dapsone-induced agranulocytosis in an Indian mid-borderline leprosy patient. Lepr Rev. 2003;74:167–70.

    PubMed  Google Scholar 

  52. Satarasinghe RL, Jayawardana MAR, De Silva GVTSK, Murugathas S, Riyaaz AAA, Wickrmasingha UDUK, et al. Total agranulocytosis caused by dapsone therapy for tuberculoid leprosy—an unappreciated serious side effect of anti-leprosy treatment with clinical implications. Drug Metabol Drug Interact. 2009;24:325–9.

    CAS  PubMed  Google Scholar 

  53. Potočnjak I, Likić R, Šimić I, Juričić Nahal D, Čegec I, Ganoci L, et al. Dapsone-induced agranulocytosis—possible involvement of low-activity N-acetyltransferase 2. Fundam Clin Pharmacol. 2017;31:580–6.

    PubMed  Google Scholar 

  54. Kobe Y, Setoguchi D, Kitamura N. Dapsone-induced agranulocytosis leading to perianal abscess and death: a case report. J Med Case Rep BioMed Central Ltd. 2011;5:107.

    Google Scholar 

  55. Besser M, Vera J, Clark J, Chitnavis D, Beatty C, Vassiliou G. Preservation of basophils in dapsone-induced agranulocytosis suggests a possible pathogenetic role for leucocyte peroxidases. Int J Lab Hematol. 2009;31:245–7.

    CAS  PubMed  Google Scholar 

  56. Milkova L, Hallermann C, Simon JC, Treudler R. Asymptomatische Dapson-induzierte Agranulozytose bei einem Patienten mit chronisch spontaner Urtikaria. JDDG J Ger Soc Dermatol. 2014;12:717–20.

    Google Scholar 

  57. Schmidt E, Kraensel R, Goebeler M, Sinkgraven R, Bröcker EB, Rzany B, et al. Treatment of bullous pemphigoid with dapsone, methylprednisolone, and topical clobetasol propionate: a retrospective study of 62 cases. Cutis. 2005;76:205–9.

    PubMed  Google Scholar 

  58. Hoffmann TK, von Schmiedeberg S, Wulferink M, Thier R, Bier H, Ruzicka T, et al. Dapsone-induced agranulocytosis. The role of xenobiotic-metabolizing enzymes demonstrated by a case report TT—Dapson-induzierte Agranulozytose. Die Rolle fremdstoffmetabolisierender Enzyme am Beispiel einer Kasuistik. Hautarzt. 2005;56:673–7.

    CAS  PubMed  Google Scholar 

  59. Coleman MD. Dapsone-mediated agranulocytosis: risks, possible mechanisms and prevention. Toxicology. 2001;162:53–60.

    CAS  PubMed  Google Scholar 

  60. Coleman MD. Dapsone toxicity: some current perspectives. Gen Pharmacol. 1995;26:1461–7.

    CAS  PubMed  Google Scholar 

  61. Uetrecht J, Zahid N, Shear NH, Biggar WD. Metabolism of dapsone to a hydroxylamine by human neutrophils and mononuclear cells. J Pharmacol Exp Ther. 1988;245:274–9.

    CAS  PubMed  Google Scholar 

  62. Kaufmann D. Severe episode of high fever with rash, lymphadenopathy, neutropenia, and eosinophilia after minocycline therapy for acne. Arch Intern Med. 1994;154:1983–4.

    CAS  PubMed  Google Scholar 

  63. Ahmed F, Kelsey PR, Shariff N. Lupus syndrome with neutropenia following minocycline therapy - A case report. Int J Lab Hematol. 2008;30:543–5.

    CAS  PubMed  Google Scholar 

  64. Berkelhammer C. Minocycline-induced hepatitis with autoimmune features and neutropenia. J Clin Gastroenterol. 1998;27:74–5.

    PubMed  Google Scholar 

  65. Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clin Ther. 2005;27:1329–42.

    CAS  PubMed  Google Scholar 

  66. Fraser GL, Beaulieu JT. Leukopenia secondary to sulfadiazine silver. JAMA. 1979;241:1928–9.

    CAS  PubMed  Google Scholar 

  67. Wilson P, George R, Raine P. Topical silver sulphadiazine and profound neutropenia in a burned child. Burns. 1986;12:295–6.

    CAS  Google Scholar 

  68. Fuller FW. The side effects of silver sulfadiazine. J Burn Care Res. 2009;30:464–70.

    PubMed  Google Scholar 

  69. Pai V, Ganavalli A, Kikkeri NN. Antifungal resistance in dermatology. Indian J Dermatol. 2018;63:361–8.

    PubMed  PubMed Central  Google Scholar 

  70. Chaudhary RG, Rathod SP, Jagati A, Zankat D, Brar AK, Mahadevia B. Oral antifungal therapy: emerging culprits of cutaneous adverse drug reactions. Indian Dermatol Online J. 2019;10:125–30.

    PubMed  PubMed Central  Google Scholar 

  71. Li L-JMS, Miller J. Terbinafine-induced neutropenia. Br J Dermatol. 1999;140:1196–7.

    PubMed  Google Scholar 

  72. Ornstein DL, Ely P. Reversible agranulocytosis associated with oral terbinafine for onychomycosis. J Am Acad Dermatol. 1998;39:1023–4.

    CAS  PubMed  Google Scholar 

  73. Gupta AK, Soori GS, Del Rosso JQ, Bartos PB, Shear NH. Severe neutropenia associated with oral terbinafine therapy. J Am Acad Dermatol. 1998;38:765–7.

    CAS  PubMed  Google Scholar 

  74. Kovacs MJ, Alshammari S, Guenther L, Bourcier M. Neutropenia and pancytopenia associated with oral terbinafine. J Am Acad Dermatol. 1994;31:806.

    CAS  PubMed  Google Scholar 

  75. Kantarcioglu B, Turkoz HK, Yilmaz G, Pepedil Tanrikulu F, Kaygusuz Atagunduz I, Adiguzel C, et al. Aplastic anemia associated with oral terbinafine: a case report and review of the literature. Turk J Haematol Off J Turk Soc Haematol. 2014;31:411–6.

    Google Scholar 

  76. Aguilar C, Mueller KK. Reversible agranulocytosis associated with oral terbinafine in a pediatric patient. J Am Acad Dermatol. 2001;45:632–4.

    CAS  PubMed  Google Scholar 

  77. Ryder NS. Terbinafine: mode of action and properties of the squalene epoxidase inhibition. Br J Dermatol. 1992;126(Suppl):2–7.

    PubMed  Google Scholar 

  78. Schultz B, Culton D. A case of late-onset neutropenia secondary to rituximab in a patient with mucous membrane pemphigoid. JAAD Case Rep. 2019;5:715–9.

    PubMed  PubMed Central  Google Scholar 

  79. Adler BL, Crew AB, Woodley DT. Early-onset neutropenia after rituximab therapy for bullous pemphigoid. Clin Exp Dermatol. 2019;44:334–6.

    CAS  PubMed  Google Scholar 

  80. Goh MSY, McCormack C, Dinh HV, Welsh B, Foley P, Prince HM. Rituximab in the adjuvant treatment of pemphigus vulgaris: a prospective open-label pilot study in five patients. Br J Dermatol. 2007;156:990–6.

    CAS  PubMed  Google Scholar 

  81. Rios-Fernández R, Gutierrez-Salmerón MT, Callejas-Rubio J-L, Fernández-Pugnaire M, Ortego-Centeno N. Late-onset neutropenia following rituximab treatment in patients with autoimmune diseases. Br J Dermatol. 2007;157:1271–3.

    PubMed  Google Scholar 

  82. Khosravi H, Abdollahi M, Badakhsh M, Soori T, Jafari M, Bae G, et al. Rituximab induced neutropenia in a patient with bullous pemphigoid. Arch Med. 2017;9:1–2.

    Google Scholar 

  83. Parodis I, Söder F, Faustini F, Kasza Z, Samuelsson I, Zickert A, et al. Rituximab-mediated late-onset neutropenia in systemic lupus erythematosus—distinct roles of BAFF and APRIL. Lupus. 2018;27:1470–8.

    CAS  PubMed  Google Scholar 

  84. Wolach O, Bairey O, Lahav M. Late-onset neutropenia after rituximab treatment: case series and comprehensive review of the literature. Medicine (Baltimore). 2010;89:308–18.

    PubMed  Google Scholar 

  85. Rajakulendran S, Gadsby K, Allen D, O’Reilly S, Deighton C. Neutropenia while receiving anti-tumour necrosis factor treatment for rheumatoid arthritis. Ann Rheum Dis. 2006;65:1678–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Jordan J, Bieber T, Wilsmann-Theis D. Rapid remission of psoriasis with reversible leucopenia after two injections with adalimumab. Clin Exp Dermatol. 2009;34:1004–5.

    Google Scholar 

  87. Lahbabi I, Adamski H, Le Jean S, Cannieux V, Polard E, Chevrant-Breton J. Neutropenia and thrombocytopenia in a patient presenting psoriasis treated with etanercept. Ann Dermatol Venereol. 2008;135:409–10.

    CAS  PubMed  Google Scholar 

  88. Bessissow T, Renard M, Hoffman I, Vermeire S, Rutgeerts P, Van Assche G. Review article: non-malignant haematological complications of anti-tumour necrosis factor alpha therapy. Aliment Pharmacol Ther. 2012;36:312–23.

    CAS  PubMed  Google Scholar 

  89. Van De Kerkhof PCM, Griffiths CEM, Reich K, Leonardi CL, Blauvelt A, Tsai TF, et al. Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2016;75(83–98):e4.

    Google Scholar 

  90. Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:345–56.

    CAS  PubMed  Google Scholar 

  91. Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373:1318–28.

    CAS  PubMed  Google Scholar 

  92. Forlow SB, Schurr JR, Kolls JK, Bagby GJ, Schwarzenberger PO, Ley K. Increased granulopoiesis through interleukin-17 and granulocyte colony-stimulating factor in leukocyte adhesion molecule-deficient mice. Blood. 2001;98:3309–14.

    CAS  PubMed  Google Scholar 

  93. Tegtmeyer K, Zhao J, Maloney NJ, Atassi G, Beestrum M, Lio PA. Off-label studies on tofacitinib in dermatology: a review. J Dermatolog Treat. 2019. https://doi.org/10.1080/09546634.2019.1673877.

    Article  PubMed  Google Scholar 

  94. Huang F, Luo Z-C. Adverse drug events associated with 5 mg versus 10 mg Tofacitinib (Janus kinase inhibitor) twice daily for the treatment of autoimmune diseases: a systematic review and meta-analysis of randomized controlled trials. Clin Rheumatol. 2019;38:523–34.

    PubMed  Google Scholar 

  95. Schulze-Koops H, Strand V, Nduaka C, DeMasi R, Wallenstein G, Kwok K, et al. Analysis of haematological changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies. Rheumatology. 2016;56:46–57.

    PubMed  Google Scholar 

  96. Friedman ES, LaNatra N, Stiller MJ. NSAIDs in dermatologic therapy: review and preview. J Cutan Med Surg. 2002;6:449–59.

    PubMed  Google Scholar 

  97. Wishner AJ, Milburn PB. Meclofenamate sodium-induced agranulocytosis and suppression of erythropoiesis. J Am Acad Dermatol. 1985;13:1052–3.

    CAS  PubMed  Google Scholar 

  98. Strom BL, Carson JL, Schinnar R, Snyder ES, Shaw M, Lundin FEJ. Nonsteroidal anti-inflammatory drugs and neutropenia. Arch Intern Med. 1993;153:2119–24.

    CAS  PubMed  Google Scholar 

  99. Klose S, Pflock R, König IR, Linder R, Schwaninger M. Metamizole and the risk of drug-induced agranulocytosis and neutropenia in statutory health insurance data. Naunyn Schmiedebergs Arch Pharmacol. 2020;393:681–90.

    CAS  PubMed  Google Scholar 

  100. Mamus SW, Burton JD, Groat JD, Schulte DA, Lobell M, Zanjani ED. Ibuprofen-associated pure white-cell aplasia. N Engl J Med. 1986;314:624–5.

    CAS  PubMed  Google Scholar 

  101. Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC. Current use and future potential role of retinoids in dermatology. Drugs. 1997;53:358–88.

    CAS  PubMed  Google Scholar 

  102. Sarkar R, Chugh S, Garg VK. Acitretin in dermatology. Indian J Dermatol Venereol Leprol. 2013;79:759–71.

    PubMed  Google Scholar 

  103. Chave TA, Mortimer NJ, Hutchinson PE. Agranulocytosis and total scalp alopecia following acitretin. Br J Dermatol. 2003;148:1063–4.

    CAS  PubMed  Google Scholar 

  104. Ozdemir MA, Kose M, Karakukcu M, Ferahbas A, Patiroglu T, Koklu E. Isotretinoin-induced agranulocytosis. Pediatr Dermatol. 2007;24:425–6.

    PubMed  Google Scholar 

  105. Waisman M. Agranulocytosis from isotretinoin. J Am Acad Dermatol. 1988;18:395–6.

    CAS  PubMed  Google Scholar 

  106. Olbricht SM, Ave B, Griffiths CEM, Street P. Leukopenia and neutropenia associated with isotretinoin therapy. Arch Dermatol. 1987;123:293–5.

    Google Scholar 

  107. Barbieri JS, Shin DB, Wang S, Margolis DJ, Takeshita J. The clinical utility of laboratory monitoring during isotretinoin therapy for acne and changes to monitoring practices over time. J Am Acad Dermatol. 2020;82:72–9.

    PubMed  Google Scholar 

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  1. Department of Medical Education, National Taiwan University Hospital, No.7, Zhongshan S. Rd Zhongzheng Dist., Taipei City 100, Taiwan, ROC

    Chang-Yu Hsieh

  2. Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, No.7, Zhongshan S. Rd Zhongzheng Dist., Taipei City 100, Taiwan, ROC

    Tsen-Fang Tsai

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  1. Chang-Yu Hsieh
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Chang-Yu Hsieh has no conflict of interest to disclose. Tsen-Fang Tsai has conducted clinical trials or received honoraria for serving as a consultant for Abbvie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli-Lilly, Galderma, Janssen-Cilag, Merck Sharp & Dohme, Novartis International AG, Pfizer Inc., and UCB Pharma.

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C-YH conducted the literature search and drafted the manuscript. T-FT provided the idea of this review and made final revisions of this article. 

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Hsieh, CY., Tsai, TF. Drug-Induced Neutropenia During Treatment of Non-Neoplastic Dermatologic Diseases: A Review. Clin Drug Investig 40, 915–926 (2020). https://doi.org/10.1007/s40261-020-00956-w

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