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Year : 2019  |  Volume : 11  |  Issue : 4  |  Page : 173-176  

Alopecia universalis in a case of rheumatoid arthritis after treatment with etanercept

Department of Dermatology, Military Hospital, Meerut, Uttar Pradesh, India

Date of Web Publication19-Aug-2019

Correspondence Address:
Dr Renu Kandpal
Department of Dermatology, Military Hospital, Meerut, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijt.ijt_22_19

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Alopecia universalis (AU) is a condition which causes generalized hair loss of the body. It is postulated that autoimmunity plays an important role in its pathogenesis. It is characterized by the involvement of multiple inflammatory cytokines such as tumor necrosis factor-alpha and multiple interferons. Hence, biologics like tumor necrosis factor alpha (TNF-α) antagonist may be used to block this inflammatory process. It is not very commonly appreciated that the use of biologics can lead to alopecia areata. Here, we report a case of severe alopecia areata which progressed to AU after etanercept administration. We here describe a 23-year-old unmarried female who was a known case of rheumatoid arthritis who developed AU after 6 months of continuous treatment with etanercept. TNF-α antagonist may not play a sufficient role in the treatment of alopecia areata. There exists a strong and significant connection between TNF-α blockers and development of alopecia and specifically AU and their role in the pathophysiology of the disease should be called into question if our findings are observed again.

Keywords: Alopecia areata, alopecia universalis, etanercept, rheumatoid arthritis

How to cite this article:
Kandpal R. Alopecia universalis in a case of rheumatoid arthritis after treatment with etanercept. Int J Trichol 2019;11:173-6

How to cite this URL:
Kandpal R. Alopecia universalis in a case of rheumatoid arthritis after treatment with etanercept. Int J Trichol [serial online] 2019 [cited 2022 May 28];11:173-6. Available from: https://www.ijtrichology.com/text.asp?2019/11/4/173/264713

   Introduction Top

Alopecia universalis (AU) is an advanced and severe form of alopecia areata which is characterized by the total loss of hair from the scalp along with the body hairs.[1] Alopecia areata affects approximately 1.7% of the population.[2] It is an autoimmune condition, and cytotoxic CD8+ T cells play a key role in its pathogenesis. These are the first cells to infiltrate the hair bulb and produce multiple cytokines such as tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ) which initiate a pro-inflammatory cascade leading to chronic inflammation of hair follicles leading to loss of hair follicle.[3] There are other factors also which play an important role in its onset. The environmental and genetic factors are important factors among these.[4]

Rheumatoid arthritis (RA) is also an autoimmune condition which is characterized by destructive arthropathy with systemic symptoms.[5] Clinically, it is characterized by painful swelling of wrist and hand joints bilaterally and symmetrically.[5] It is usually insidious in onset, and gradually progressive disease and chronic condition may lead to complete destruction of joint, deformity, and anatomical and functional impairment. The pathogenesis of the disease is very complex involving an autoimmune reaction.[6] It is characterized by the collection of inflammatory cells such as T cells, B cells, monocytes, macrophages, fibroblasts, and neutrophils which lead to the abnormal production of cytokines and other inflammatory mediators. These cytokines elicit inflammation of synovial membranes leading to the swelling of joints. Persistent inflammation leads to systemic inflammation leading to the involvement of many other visceral organs of the body.

The development of AU as an adverse effect is observed rarely after using TNF-α inhibitors in case of RA. In our case report, we are describing a 23-year-old female patient, a known case of RA, who after treatment with etanercept developed alopecia areata followed by AU. Moreover, when it was stopped, no significant improvement is seen in alopecia. It is believed that when etanercept was given it led to the blockade of action of TNF-α and the only cytokine that remained was IFN-α which promoted inflammation in hair bulb leading to hair loss. Hence, if such situation arises, we have to look for benefit or risk ratio of initiation, continuation, and discontinuation of the therapy.

   Case Report Top

A 23-years-old female who is a known case of RA from the age of 16 years and was on regular treatment for the same was referred to skin department by the rheumatologist, with complaints of loss of all hairs from the scalp and the body for the past 12 months. The patient denied having similar complaints before. According to the patient, she had been treated with multiple therapies for joint pains and swelling. Initially, she was managed with nonsteroidal anti-inflammatory drugs, along with oral methotrexate for approximately 4 years to which she was responding well. However, after 4 years, in spite of regular treatment, she gradually started developing deformities of hands and feet for which her rheumatologist started her on subcutaneous injection etanercept once fortnightly for initial 3 months and then once monthly for next 3 months leading to a marked improvement in her arthritis. After 6 months of the treatment, the patient gradually started losing her hair from the scalp followed by other body hairs. After observing this, her rheumatologist referred the patient to our clinic. The patient does not give any other history of triggering factors such as any kind of stress, infection, or trauma.

Her dermatological examination revealed multiple patches of nonscarring alopecia along with the presence of few thin, pigmented hairs on the scalp and complete absence of hair in axilla, pubic region and other body parts as shown in [Figure 1], [Figure 2], [Figure 3], [Figure 4].
Figure 1: Complete loss of hairs from parietal region of scalp

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Figure 2: Complete loss of hair from frontal region of scalp

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Figure 3: Complete loss of hair from axilla

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Figure 4: Regrowth of scalp hair after starting of oral steroid mini pulse therapy

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Biopsy of scalp showed the presence of miniaturization of the hair with peribulbar infiltrate as shown in [Figure 5]. On doing dermoscopy of the scalp, it demonstrated the presence of black dots, yellow spots, and dystrophic hair [Figure 6]. The patient had a normal thyroid profile and normal vitamin D3 level. The patient was started on oral mini-pulse of steroid and topical treatment with minoxidil 5%. After 3 months, she started regaining hair of scalp in a patchy pattern, but no hair growth was observed in other body parts.
Figure 5: Histopathology section shows perifollicular inflammatory infiltrate

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Figure 6: Dermoscopy of scalp shows yellow and black dots

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In our case, we made a diagnostic hypothesis of AU which is stimulated by the use of anti-TNF drug etanercept.

The decision to stop etanercept was made after consulting her rheumatologist.

   Discussion Top

AU is a known dermatological condition which is characterized by the complete loss of hair on the scalp and body. In other words, it can be said that it is an advanced type of alopecia areata.[1],[2],[3] There are different hypothesis supporting its pathogenesis, but according to the most widely accepted one, it is an autoimmune condition which is characterized by the activation of immune system against the hair follicles.[7] This lead to the reaction of CD4 and CD8 T cells of the immune system with autoantigens of hair bulb initiating an inflammatory reaction. This ultimately leads to the expression of multiple pro-inflammatory cytokines such as TNF-α, IFN-gamma, and various other Th1 chemokines such as CXCL9 and CXCL10.[8],[9] All these lead to the suppression of immunosuppressive environment around the hair bulb leading to immune activation and further hair loss.[10],[11]

Similarly, RA is also an inflammatory autoimmune condition which is characterized by bone and systemic involvement. Its pathophysiology also involves the interaction of T and B cells along with pro-inflammatory cytokines like TNF-α and interleukin (IL-1) IL-6; IL-17, etc.[11],[12]

In this respect, due to the similar pathophysiology, alopecia areata is found to be associated with autoimmune diseases like RA, and it also suggests that TNF-α and IFNs play an important role in cases of autoimmunity.[13] The development of biologic medications has raised high hopes for effective control of many immune-mediated diseases. Hence, one might expect an excellent response on both RA and alopecia areata with anti-TNF-α drugs. However, in our case, when etanercept was started for RA, it was surprising that alopecia areata occurred and it gradually progressed to become AU. Furthermore, the alopecia had been somewhat treatment resistant. Hence, this alopecia appears paradoxical, because TNF-α inhibits hair growth. However, this paradoxical reaction also suggests that it might be possible that autoimmunity is mediated by blockade of regulatory T cells.[13],[14],[15] Hence, our case along with observation of Lazzarin et al.,[16] Posten and Swan,[17] Strober et al.,[18] Pelivani et al.[19] indicate that etanercept can trigger alopecia in predisposed individuals. Along with this, onset or worsening of alopecia has been found with other TNF-alpha antagonist such as infliximab and adalimumab.[20],[21] One report by Navarro et al. described RA treated with leflunomide alone can trigger the alopecia.[22] Based on these studies and literature data, there is a clear indication that there is some relation between both the events. According to a study done by Ostojic and Pavlov-Dolijanovic when TNF-alpha blockers are given, the main cytokine that may be involved in promoting inflammation is IFN-α.[23] On the basis of all these studies, it can be suggested that perhaps after using biologicals, the expression of various cytokines is altered which lead to decreased or no hair growth.

   Conclusion Top

The aim to report this case is that there are number of patients who are undergoing treatment with drugs which have anti-TNF properties. Hence, it becomes important to have the knowledge and reporting of associated adverse effects. It also suggests that TNF-α may not be the most important factor for the development of the disease; so, it really becomes essential to review again the role of T cells and the pro-inflammatory cytokines in the pathophysiology of AU and role of biologicals as its therapy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names 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


Conflicts of interest

There are no conflicts of interest.

   References Top

Darwin E, Hirt PA, Fertig R, Doliner B, Delcanto G, Jimenez JJ. Alopecia areata: Review of epidemiology, clinical features, pathogenesis, and new treatment options. Int J Trichology 2018;10:51-60.  Back to cited text no. 1
Safavi K. Prevalence of alopecia areata in the first national health and nutrition examination survey. Arch Dermatol 1992;128:702.  Back to cited text no. 2
van der Steen P, Traupe H, Happle R, Boezeman J, Sträter R, Hamm H. The genetic risk for alopecia areata in first degree relatives of severely affected patients. An estimate. Acta Derm Venereol 1992;72:373-5.  Back to cited text no. 3
Colombe BW, Lou CD, Price VH. The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis. J Investig Dermatol Symp Proc 1999;4:216-9.  Back to cited text no. 4
Barton A, Worthington J. Genetic susceptibility to rheumatoid arthritis: An emerging picture. Arthritis Rheum 2009;61:1441-6.  Back to cited text no. 5
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011;365:2205-19.  Back to cited text no. 6
Cho HH, Jo SJ, Paik SH, Jeon HC, Kim KH, Eun HC, et al. Clinical characteristics and prognostic factors in early-onset al opecia totalis and alopecia universalis. J Korean Med Sci 2012;27:799-802.  Back to cited text no. 7
Islam N, Leung PS, Huntley AC, Gershwin ME. The autoimmune basis of alopecia areata: A comprehensive review. Autoimmun Rev 2015;14:81-9.  Back to cited text no. 8
Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: Part I. Clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol 2010;62:177-88.  Back to cited text no. 9
Bertolini M, Zilio F, Rossi A, Kleditzsch P, Emelianov VE, Gilhar A, et al. Abnormal interactions between perifollicular mast cells and CD8+ T-cells may contribute to the pathogenesis of alopecia areata. PLoS One 2014;9:e94260.  Back to cited text no. 10
Paus R, Slominski A, Czarnetzki BM. Is alopecia areata an autoimmune-response against melanogenesis-related proteins, exposed by abnormal MHC class I expression in the anagen hair bulb? Yale J Biol Med 1993;66:541-54.  Back to cited text no. 11
Ito T, Ito N, Bettermann A, Tokura Y, Takigawa M, Paus R. Collapse and restoration of MHC class-I-dependent immune privilege: Exploiting the human hair follicle as a model. Am J Pathol 2004;164:623-34.  Back to cited text no. 12
McDonagh AJ, Messenger AG. The pathogenesis of alopecia areata. Dermatol Clin 1996;14:661-70.  Back to cited text no. 13
Gabriel SE, Michaud K. Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res Ther 2009;11:229.  Back to cited text no. 14
Zschoche C, Bidier M, Hadaschik E. Alopecia areata during treatment with adalimumab: Therapy with an alternative TNF-alpha inhibitor is possible. J Dtsch Dermatol Ges 2013;11:450-3.  Back to cited text no. 15
Lazzarini R, Capareli GC, Buense R, Lellis RF. Alopecia universalis during treatment with leflunomide and adalimumab – Case report. An Bras Dermatol 2014;89:320-2.  Back to cited text no. 16
Posten W, Swan J. Recurrence of alopecia areata in a patient receiving etanercept injections. Arch Dermatol 2005;141:759-60.  Back to cited text no. 17
Strober BE, Siu K, Alexis AF, Kim G, Washenik K, Sinha A, et al. Etanercept does not effectively treat moderate to severe alopecia areata: An open-label study. J Am Acad Dermatol 2005;52:1082-4.  Back to cited text no. 18
Pelivani N, Hassan AS, Braathen LR, Hunger RE, Yawalkar N. Alopecia areata universalis elicited during treatment with adalimumab. Dermatology 2008;216:320-3.  Back to cited text no. 19
Tosti A, Pazzaglia M, Starace M, Bellavista S, Vincenzi C, Tonelli G. Alopecia areata during treatment with biologic agents. Arch Dermatol 2006;142:1653-4.  Back to cited text no. 20
Garcia Bartels N, Lee HH, Worm M, Burmester GR, Sterry W, Blume-Peytavi U. Development of alopecia areata universalis in a patient receiving adalimumab. Arch Dermatol 2006;142:1654-5.  Back to cited text no. 21
Navarro R, Daudén E, Gallo E, Santiago Sánchez-Mateos D, García-Diez A. Alopecia areata during treatment of psoriasis with adalimumab and leflunomide: A case and review of the literature. Skin Pharmacol Physiol 2012;25:107-10.  Back to cited text no. 22
Ostojic P, Pavlov-Dolijanovic S. Alopecia universalis in a patient with rheumatoid arthritis developed during treatment with adalimumab. Z Rheumatol 2018;77:412-5.  Back to cited text no. 23


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

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