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Alopecia Areata and Severe Psoriasis Successfully Treated with Apremilast

Archives of Clinical Dermatology. 2017;1(1):2
DOI: 10.24983/scitemed.acd.2017.00033
Article Type: Case Report


Alopecia areata is a T-cell mediated autoimmune disease of nonscarring hair loss with no effective treatment that induces and sustains remission. Apremilast, a small molecule inhibitor of PDE4 approved for the treatment of psoriasis and psoriatic arthritis, showed rapid and extensive scalp-hair regrowth in a patient who had psoriasis and ophiasic alopecia areata.


  • Alopecia areata; psoriasis; phosphodiesterase 4 inhibitors.


The association between alopecia areata (AA) and psoriasis is a well-known but rare condition [1]. AA management in daily clinical practice remains unsatisfactory. We report herein, for the first time, a patient who had remarkably extensive scalp-hair growth while she had been receiving Apremilast for psoriasis localized in the scalp and body.

Case Report

A 57-year-old woman with a seven-year history of psoriasis and psoriatic arthritis was referred to our department, because at the time of psoriasis, she had also developed ophiasic alopecia areata. Psoriasis was treated with topical steroids, vitamin D analogues, UVB narrow band, and methotrexate, but they were ineffective. Treatment for alopecia areata included topical clobetasol propionate and minoxidil 5%, but there was no remarkable hair growth.

Dermatological examination revealed typical psoriasis plaques in both alopecic and non-alopecic areas of the scalp, arms, and trunk with initial Psoriasis Area and Severity Index (PASI) of 12, Body Surface Area (BSA) of 16, Physician's Global Assessment (PGA) of 3, and Scalp PGA of 4. It was remarkable that the patient complained of very severe itching (Itch Numeric Rating Scale of 8) and extensive hair loss of the temporal, parietal, and occipital regions of the scalp (Fig. 1).

Figure 1. Ophiasic alopecia areata before treatment with Apremilast.


There was no family history of AA or psoriasis. Rheumatologist consultation and radiography confirmed the diagnosis of psoriatic arthritis. Laboratory findings showed no abnormalities.

Treatment with Apremilast was started as label dosing, and after 6 weeks the patient showed significant improvement in psoriasis lesions with reduced erythema and scaling, and marked improvement of pruritus. Interestingly, significant hair regrowth was seen on the scalp (Fig. 2), and with the ongoing Apremilast therapy, hair continued to grow until it achieved complete regrowth.

Figure 2. Significant scalp-hair regrowth after 6 weeks with Apremilast. 


The patient developed diarrhea attributed to Apremilast since the first week, and subsequently weight loss (seven kilograms in 8 weeks). As the patient declined to stop the treatment, the drug use was continued, associating it with an oral antidiarrheal agent as loperamide and probiotics.

After twelve weeks, there was a successful hair regrowth on the scalp, in particular, in the areas with psoriasis lesions. The patient`s scalp hair was approximately 5 cm long with no remaining patches of AA (Fig. 3). Alopecia areata and psoriasis scalp were completely resolved. As the gastrointestinal side effects remained despite the complementary treatment, the patient agreed to stop the treatment. Six months later, the patient is still asymptomatic.

Figure 3. Total scalp-hair regrowth with a cosmetically important response after 12 weeks with Apremilast. 


While many factors have been implicated in the pathogenesis of AA, it is now clear that the immune system is the major player, with T cells and a collapse of the physiological immune privilege of the hair follicle playing critical roles [2]. Although the Th1 pathway has been suggested as pivotal in the disease, recent studies suggest that Th2, Th9, phosphodiesterase (PDE) 4, and IL-23 axes might contribute to AA pathogenesis [3]. Animal models have greatly helped to elucidate critical cellular and molecular immune pathways in AA. Instead, a humanized mouse model of AA has been used to demonstrate the previously hypothesized key role of CD8+ T cells and NKG2D+ cells in AA pathogenesis [4].

PDE4 inhibitors (Apremilast) showed very recently the efficacy in treating AA in a humanized AA mouse model that employs normal human scalp skin and PBMCs from healthy donors that are transplanted onto SCID/Beige mice [5]. In that paper, the group of mice treated with Apremilast showed almost complete absence of CD8+, NKG2D+ cells and reduced production of pro-inflammatory cytokines, such as IFN-gamma and TNF-alpha. PDE4 was also highly increased in human AA lesions.

Psoriatic alopecia is difficult to distinguish from AA [6]. The frequency of AA, the ophiasic pattern of the alopecia in our patient, and the presence of yellow dots in the dermoscopy led us to consider the diagnosis of AA as more probable. The gastrointestinal side effects were also remarkable in our patient. Although the weight loss was thought to be independent of diarrhea, and usually it was found to be 1.5 kg on average over a one-year period, we thought this was not the case in our patient, and we finally decided to stop the treatment [7, 8].


In this case report, it was interesting to observe the amazing effectiveness of Apremilast in refractory ophiasis AA with a rapid and highly scalp-hair regrowth with a cosmetically important response.


  1. Khaled A, Hawilo A, Zaouak A et al. Association between scalp psoriasis and alopecia areata. Tunis Med 2012;90:344. PMID: 22535354
  2. Dainichi T and Kabashima K. Alopecia areata: What’s new in epidemiology, pathogenesis, diagnosis, and therapeutic options? Journal of Dermatological Science 2017;86:3-12. PMID: 27765435; DOI: 10.1016/j.jdermsci.2016.10.004
  3. Renert-Yual Y and Guttman-Yassky E. A novel therapeutic paradigm for patients with extensive alopecia areata. Expert Opinion on Biological Therapy 2016;16:1005-1014. PMID: 27164008; DOI: 10.1080/14712598.2016.1188076 
  4. Gilhar A, Schrum AG, Etzioni A, Waldmann H and Paus R. Alopecia areata: Animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies. Autoimmunity Review 2016;15:726-735. PMID: 26971464; PMCID: PMC5365233 DOI: 10.1016/j.autrev.2016.03.008
  5. Keren A, Shemer A, Ullmann Y, et al. The PDE4 inhibitor, apremilast, suppresses experimentally induced alopecia areata in human skin in vivo. Journal of Dermatological Science 2015;77:74–76. PMID: 25530115; DOI: 10.1016/j.jdermsci.2014.11.009
  6. George SM, Taylor MR and Farrant PB. Psoriatic alopecia. Clinical and Experimental Dermatology 2015;40:717-721. PMID: 26202646; DOI: 10.1111/ced.12715
  7. Reich K, Gooderham M, Green L et al. The efficacy and safety of apremilast, etanercept and placebo in patients with moderate-to-severe plaque psoriasis: 52-week results from a phase IIIb, randomized, placebo-controlled trial (LIBERATE). Journal of the European Academy of Dermatology and Venereology 2017;31:507-517. DOI: 10.1111/jdv.14015
  8. Crowley J, Thaçi D, Joly P et al. Long-term safety and tolerability of apremilast in patients with psoriasis: Pooled safety analysis for ≥156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2). Journal of the American Academy of Dermatology 2017;77:310-317. DOI: 10.1016/j.jaad.2017.01.052

Editorial Information

Publication History

Received date: July 07, 2017
Accepted date: August 28, 2017
Published date: September 27, 2017


© 2017 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY).

Department of Dermatology, Central University Hospital of Asturias, Oviedo, Spain
Department of Dermatology, Central University Hospital of Asturias, Oviedo, Spain
Department of Dermatology, Central University Hospital of Asturias, Oviedo, Spain
Department of Dermatology, Central University Hospital of Asturias, Oviedo, Spain
Department of Dermatology, Central University Hospital of Asturias, Oviedo, Spain
Figure 1.JPG
Figure 1. Ophiasic alopecia areata before treatment with Apremilast.
Figure 2.JPG
Figure 2. Significant scalp-hair regrowth after 6 weeks with Apremilast.
Figure 3.JPG
Figure 3. Total scalp-hair regrowth with a cosmetically important response after 12 weeks with Apremilast.

Peer Review Report: Round 1

Reviewer 1 Comments 

  1. The relationship between psoriasis and AA is unclear in this case. Looking at Figure 1, it appears that psoriasis lesions were present in almost all areas affected by hair loss. Since psoriatic alopecia (George SM, et al. Psoriatic alopecia. Clin Exp Dermatol. 2015; 40:717-21) is difficult to distinguish from AA and can affect even areas not affected by psoriasis, the question remains how the diagnosis was confirmed. Were biopsies taken before therapy?
    ResponseWe agree with the reviewer’s comment regarding the concern about the differential diagnosis between psoriatic alopecia and AA. The ophiasic pattern and the presence of yellow dots in the dermoscopy exploration led us to consider the diagnosis of AA as more probable. Unfortunately, biopsy specimen was not taken. To assess this controversy, we included this point in the new version of the paper.
  2. Knowing the slow onset of response of psoriasis to apremilast (Papp K, et al. J Am Acad Dermatol. 2015; 73:37-49), it is surprising to see that after 6 weeks (Figure 2) the scalp psoriasis seems to have almost completely resolved. It is also surprising to see several centimeter long hairs in the previously bald areas in light of the usual latency between onset of successful AA treatment and hair regrowth and an expected growth rate of 1 cm/month.
     ResponseWe agree with the reviewer’s comment about considering as exceptional response of the patient´s scalp psoriasis and recovering of the hair with apremilast. In fact, that is one of the reasons encouraging us to communicate it. In our experience, the response to apremilast in scalp, palms and soles is not as slow as in the rest of the body.
  3. Apremilast is known to induce weight loss independent of diarrhea and patients usually lose 1.5 kg on average over a one-year period (Reich K, et al. J Eur Acad Dermatol Venereol. 2017; 31:507-517; Crowley J, et al. J Am Acad Dermatol. 2017; 77:310-317). To hear that this patient lost 7 kg in eight weeks (!) is, therefore, worrying, and if associated with diarrhea, should have probably led to the termination of apremilast treatment.
    This side effect was reported to the Agencia Española del Medicamento (AEMPS). Although the patient initially denied to give up the treatment, after her psoriasis and AA were completely recovered, we interrupted the treatment. Six months after that the patient remains asymptomatic. This is not the only patient who experienced a significant loss of weight since the first week of the treatment.

Reviewer 2 Comments 

  1. Based on the observation, if the author believes in the finding and the rationale, the author should recommend further studies.  
    ResponseModifications have been done as per the suggestions; thanks.

Peer Review Report: Round 2

Reviewer 1 Comments

The revised article can be accepted for publication. 

Reviewer 2 Comments

The article is accepted.