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Table of Contents
CASE REPORT
Year : 2022  |  Volume : 26  |  Issue : 3  |  Page : 48-50

Peripheral neuropathy associated with tofacitinib use in alopecia universalis


1 College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
2 Department of Dermatology, King Abdulaziz Medical City, Riyadh, Saudi Arabia

Date of Submission01-Nov-2019
Date of Decision17-May-2020
Date of Acceptance05-Aug-2020
Date of Web Publication22-Aug-2022

Correspondence Address:
Dr. Fatimah Alowirdi
Department of Dermatology, King Abdulaziz Medical City, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdds.jdds_69_19

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  Abstract 

Alopecia areata (AA) is an autoimmune disease characterized by nonscarring hair loss. Alopecia universalis (AU) is the advanced form of AA characterized by complete scalp and body hair loss. Traditional medical therapies for AA include topical and intralesional corticosteroids, topical anthralin immunotherapy, and light therapy. Tofacitinib is a Janus kinase-1 and 3 inhibitor used in the treatment of AA. In this report, we describe a 20-year-old female with AU refractory to topical therapies; thus, she was started on tofacitinib. Mild peripheral neuropathy was an unanticipated side effect that could be kept into consideration.

Keywords: Alopecia, Janus kinase-1 inhibitor, Janus kinase-3 inhibitor, peripheral neuropathy, tofacitinib


How to cite this article:
Alharthi R, Alowirdi F, Alsuhaymi S, AlQahtani M, Alsheikh A. Peripheral neuropathy associated with tofacitinib use in alopecia universalis. J Dermatol Dermatol Surg 2022;26, Suppl S1:48-50

How to cite this URL:
Alharthi R, Alowirdi F, Alsuhaymi S, AlQahtani M, Alsheikh A. Peripheral neuropathy associated with tofacitinib use in alopecia universalis. J Dermatol Dermatol Surg [serial online] 2022 [cited 2022 Dec 8];26, Suppl S1:48-50. Available from: https://www.jddsjournal.org/text.asp?2022/26/3/48/354317


  Introduction Top


Alopecia areata (AA) is an autoimmune disease characterized by nonscarring hair loss. It can present at any age and affects both genders equally. The worldwide incidence of AA is estimated to be 2%.[1] Alopecia universalis (AU) is the advanced form of AA characterized by complete scalp and body hair loss.[2] Autoimmune disorders such as vitiligo and thyroid conditions are associated with AA and AU. Furthermore, severe forms of AA and AU can be seen in children with eczema.[3]

The cause and mechanisms of AA have not been completely understood. However, several factors play a role in their pathogenesis including genetic predisposition, autoimmunity, and environmental precipitators.[1],[4]

Traditional medical therapies for AA include topical and intralesional corticosteroids, topical anthralin immunotherapy, and light therapy. Systemic medications such as corticosteroids, cyclosporine, and methotrexate have been used for severe forms; however, their side effects and high relapse rate limited their use.[1] Recent medications that have been used include Janus kinase (JAK) inhibitors (tofacitinib and ruxolitinib).[5] Tofacitinib is a JAK-1 and JAK-3 inhibitor approved for the treatment for rheumatoid arthritis and is effective for AA.[6],[7] Common adverse effects of JAK inhibitors comprise infections, headache, diarrhea, and abnormalities in lipid and liver profiles.[8],[9] A rare side effect of tofacitinib observed in two cases of rheumatoid arthritis is peripheral neuropathy.[10] In this report, we describe a 20-year-old female with AU refractory to topical therapies; thus, she was started on tofacitinib. Mild peripheral neuropathy was an unanticipated side effect.


  Case Report Top


A 20-year-old female with atopic dermatitis presented to our clinic with a 3-year history of AU. On examination, she had a generalized total loss of hair including eyelashes and eyebrows. She had tried diphencyprone, intralesional steroids, and narrow-band ultraviolet B phototherapy with a suboptimal response. Basic laboratory workup was normal including complete blood count, serum electrolytes, renal function, liver function, and lipid profile (only mildly high low-density lipoprotein). After she failed a trial of anthralin 1% cream along with minoxidil 5% solution, she was started on tofacitinib 5 mg twice daily alongside minoxidil 5%. Hair began to regrow on the scalp, eyebrows, eyelashes, and forearms by her 4-month follow-up visit. The initial side effects encountered were diarrhea and gastritis. Although 80% of hair regrew after 9 months of treatment, she reported mild-to-moderate numbness in her distal upper limbs along with action tremors in the hands, headache, and loss of appetite. There was no reported limb weakness or other neurological deficits. Tofacitinib was discontinued, and she was given anthralin 5% cream and tacrolimus 0.1% ointment. Her neurologic condition improved after 3 months of stopping tofacitinib. Tests for anti-double-stranded DNA antibody, antinuclear antibodies, thyroid-stimulating hormone, Vitamin B12, and complement levels (C3 and C4) were all within the normal ranges. Electromyography and nerve conduction studies done 3 months after discontinuation of tofacitinib were normal.


  Discussion Top


Tofacitinib is a JAK inhibitor (specifically JAK1 and JAK3) indicated for the treatment of a number of immune diseases such as rheumatoid arthritis.[11] In dermatology, tofacitinib has been used for the treatment of AA, psoriasis, psoriatic arthritis, vitiligo, and atopic dermatitis when other treatment options have been inadequate or intolerable.[11] Tofacitinib is effective and relatively safe in several studies.[12],[13],[14] In a study including rheumatoid arthritis patients, the long-term safety profile was sustained up to 9.5 years.[13] The adverse effects of tofacitinib and other JAK inhibitors include infections (more commonly herpes zoster and upper respiratory tract infections), gastrointestinal symptoms, increased lipid levels, abnormal liver function tests, and hematological abnormalities.[11],[13]

We found one case report linking tofacitinib and peripheral neuropathy in two female rheumatoid arthritis patients.[10] In the report, patients experienced peripheral neuropathy symptoms (limb dysesthesias and muscle weakness) within less than a month of starting tofacitinib treatment, while our patient started complaining of her symptoms (distal upper limb numbness and action tremors in the hands) at the 9th-month visit after treatment initiation. Our patient's clinical symptoms resolved after 3 months of tofacitinib discontinuation; however, in the previously mentioned report, the patient's clinical improvement was achieved 1 month after cessation of tofacitinib.[10] It is imperative to keep in mind that rheumatoid arthritis patients might concurrently receive tumor necrosis factor inhibitors, which increase the risk of acquiring peripheral neuropathy.[15] Another medication of a similar class, momelotinib, a JAK1 and JAK2 inhibitor, induced peripheral neuropathy in 44% of myelofibrosis patients in one study in 2015.[16] Nonetheless, no cases of AA patients on tofacitinib were reported to develop peripheral neuropathy during the course of treatment. Since both momelotinib and tofacitinib appear to induce peripheral neuropathy, this effect may be mediated through JAK-1, a signaling pathway they have in common.[11] Moreover, JAK inhibitors have a neuromodulatory effect on sensory neurons, ultimately affecting itch sensation.[17],[18] Currently, there is an ongoing cohort study evaluating pain sensation in rheumatoid arthritis patients receiving tofacitinib that might provide further insight.[19] In conclusion, peripheral neuropathy might be an adverse effect of tofacitinib. Hence, observation and anticipation of neurological symptoms may be warranted.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that their name and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: A systematic review. Clin Cosmet Investig Dermatol 2015;8:397-403.  Back to cited text no. 1
    
2.
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Thomas EA, Kadyan RS. Alopecia areata and autoimmunity: A clinical study. Indian J Dermatol 2008;53:70-4.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
McElwee KJ, Gilhar A, Tobin DJ, Ramot Y, Sundberg JP, Nakamura M, et al. What causes alopecia areata? Exp Dermatol 2013;22:609-26.  Back to cited text no. 4
    
5.
Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med 2014;20:1043-9.  Back to cited text no. 5
    
6.
Hernandez-Montoya C, Ruiz-Villaverde R. The role of tofacitinib in the management of alopecia totalis. Sultan Qaboos Univ Med J 2019;19:e77-8.  Back to cited text no. 6
    
7.
Craiglow BG, Liu LY, King BA. Tofacitinib for the treatment of alopecia areata and variants in adolescents. J Am Acad Dermatol 2017;76:29-32.  Back to cited text no. 7
    
8.
FDA, CDER. Medication Guide Xeljanz (ZEL' JANS') (tofacitinib). Available from: https://www.fda.gov/media/85196/download. [Last accessed on 2020 Jun 26].  Back to cited text no. 8
    
9.
FDA. Highlights of Prescribing Information. Available from: http://www.fda. gov/medwatch. [Last accessed on 2020 Jun 26].  Back to cited text no. 9
    
10.
Navarro EP, Posso-Osorio I, Aguirre-Valencia D, Naranjo-Escobar J, Tobón GJ. Tofacitinib and Risk of Peripheral Neuropathy? Experience of 2 Cases in Patients with Rheumatoid Arthritis. Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 2018.  Back to cited text no. 10
    
11.
Chaplin S. Janus kinase inhibitors for autoimmune disorders. Prescriber. 2017;28:33-7.  Back to cited text no. 11
    
12.
Liu LY, King BA. Tofacitinib for the treatment of severe alopecia areata in adults and adolescents. J Investig Dermatol Symp Proc 2018;19:S18-S20.  Back to cited text no. 12
    
13.
Wollenhaupt J, Lee EB, Curtis JR, Silverfield J, Terry K, Soma K, et al. Safety and efficacy of tofacitinib for up to 9.5years in the treatment of rheumatoid arthritis: Final results of a global, open-label, long-term extension study. Arthritis Res Ther 2019;21:89.  Back to cited text no. 13
    
14.
Kennedy Crispin M, Ko JM, Craiglow BG, Li S, Shankar G, Urban JR, et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight 2016;1:e89776.  Back to cited text no. 14
    
15.
Etminan M, Sodhi M, Samii A, Carleton BC, Kezouh A, Antonio Avina-Zubieta J. Tumor necrosis factor inhibitors and risk of peripheral neuropathy in patients with rheumatic diseases. Semin Arthritis Rheum 2019;48:1083-6.  Back to cited text no. 15
    
16.
Abdelrahman RA, Begna KH, Al-Kali A, Hogan WJ, Litzow MR, Pardanani A, et al. Momelotinib treatment-emergent neuropathy: Prevalence, risk factors and outcome in 100 patients with myelofibrosis. Br J Haematol 2015;169:77-80.  Back to cited text no. 16
    
17.
Fukuyama T, Ganchingco JR, Mishra SK, Olivry T, Rzagalinski I, Volmer DA, et al. Janus kinase inhibitors display broad anti-itch properties: A possible link through the TRPV1 receptor. J Allergy Clin Immunol 2017;140:306-9000.  Back to cited text no. 17
    
18.
Oetjen LK, Mack MR, Feng J, Whelan TM, Niu H, Guo CJ, et al. Sensory neurons Co-opt classical immune signaling pathways to mediate chronic itch. Cell 2017;171:217-28.e13.  Back to cited text no. 18
    
19.
Schaeverbeke T. Evaluation of Pain Sensitization in Rheumatoid Arthritis: Analysis on a Cohort of Tofacitinib Treated Patients. ClinicalTrials.gov. Available from: https://clinicaltrials.gov/ct2/show/NCT03815578 [Last accessed on 2020 Aug 19].  Back to cited text no. 19
    




 

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