Alopecia Areata Treated with Oral Azathioprine: A Case Series.

Alopecia areata is commonly encountered non scarring alopecia with clinical presentations ranging from localised bald patches to extensive involvement. Clinical course is variable ranging from self limiting disease to chronic relapsing and recalcitrant disease. Topical and oral corticosteroids; nonetheless being front line agents for the treatment of alopecia areata;are not advocated for long term administration due to potentially undesirable systemic side effects. Hence the need of steroid sparing immunosuppresive agents like Azathioprine is warranted which have desired therapeutic action without much systemic adverse effects. We report a case series of 4 patients of alopecia areata treated with systemic azathioprine monotherapy. Copyright:

INTRODUCTION

Alopecia areata is a commonly encountered autoimmune condition which may present with wide spectrum of clinical presentations ranging from single or few smooth bald patches involving frontovertical or temporal areas to almost near-total or complete hair loss. Histologically, it reveals perifollicular T-cell colonization which prevents eruption of hair follicle to skin surface.

Although asymptomatic, cosmetic unacceptability associated with the condition is distressing for the patients and frequently the reason for seeking medical consultation. Mostly, topical or locally intensive treatment modalities are resorted to for the treatment of segmental or patchy involvement in alopecia areata. Given the frequent recurrences associated with natural course of the disease, local treatment measures such as topical steroids and topical minoxidil do not offer therapeutic benefits of long-term remissions.

Hence, widening our therapeutic horizons with prescription of reserve immunosuppressive drugs (like oral azathioprine) in armamentarium is warranted nowadays to interrupt progression of the disease and achieve longer remissions.

We report a case series of four patients of alopecia areata treated with systemic azathioprine monotherapy.

CASE REPORTS

Case 1

An 8-year-old female patient with recurrent patches of alopecia areata involving the scalp. She had received pulse oral and topical steroids with complete recovery recurrence followed after withdrawal of oral corticosteroids

Clinical examination revealed multiple patches of alopecia areata with partial areas of regrowth in the frontovertical area of the scalp. She was given a course of tapering regimen of oral betamethasone with good recovery. After 2 months of remission, she again reported recurrence in the form of multiple patches of alopecia areata

Line of management was shifted to oral azathioprine considering the long-term steroid she had received, given in the dose of 25 mg daily (1 mg/kg). She reported good hair growth by 4 weeks. On background of frequent episodes of recurrence reported in natural course of the disease, azathioprine was continued for 6 months, which resulted in remission [Figure 1]. After 6 months, azathioprine was discontinued and the patient was maintained on topical minoxidil.

Figure 1

Pre- and posttreatment photographs of an 8-year-old female patient showing regrowth after 6 months of azathioprine (1 mg/kg)

Case 2

A 13-year-old female patient presented with recurrent alopecia areata involving the frontovertical area of the scalp

For a span of the last 1 year, the patient had received oral betamethasone for 20 days and betamethasone pulse for 4 months

The patient reported adverse effects of oral corticosteroids in the form of increased appetite and weight gain

After withdrawal or oral steroids, the patient could maintain remission only for a month and subsequently reported recurrence

Tablet azathioprine 25 mg daily (1 mg/kg; weight 30 kg) was started along with 2 weeks oral steroid to which the patient responded with substantial hair growth [Figure 2]

Figure 2

Pretreatment and follow-up photographs of a 13-year-old female patient showing regrowth after 6 months of oral azathioprine 25 mg daily

Azathioprine was continued for 6 months which maintained the hair growth.

Case 3

An 11-year-old female presented with alopecia totalis of 1-year duration along with concomitant acral vitiligo for 2 months

She reported multiple episodes of alopecia areata in early childhood and had received multiple cocktail treatment regimens in the past for the same including oral steroids and immunosuppressive, topical immunomodulators and contact sensitizers for her alopecia without much improvement

Considering the clinical profile of alopecia areata coexisting with acral vitiligo, short-course oral betamethasone regimen (20 days) along with oral azathioprine daily 25 mg was planned

The patient reported appreciable hair growth within 4 weeks [Figure 3] and is being continued on oral azathioprine for 8 months to continue remission.

Figure 3

Regrowth seen after 8 months of oral azathioprine 25 mg in an 11-year-old female patient with alopecia subtotalis and acral vitiligo

Case 4

A 2-year-old female child presented with extensive alopecia areata (subtotalis) of over 1-year duration, with only few patches of hairy areas left

Hair regrowth was evident on treatment with oral betamethasone for 20 days good hair growth, but after steroid withdrawal turned up with recurrence. She had received four such short courses of oral steroid within 1 year, which ended up with recurrence after withdrawal of drug

Considering the extensive pattern of involvement in the child and potential adverse effects pertaining to bone involvement, especially of epiphyseal growth associated with oral corticosteroids in pediatric age group, oral azathioprine was given in the dosage of 1 mg/kg, which yielded in noticeable hair growth [Figure 4]

Figure 4

Pre- and posttreatment photos showing regrowth in a 2-year-old female child with alopecia subtotalis after 4 years of azathioprine daily (1 mg/kg)

Attempts to stop the azathioprine would result in resumption of hair loss. Hence, she is being maintained on once a week 25 mg for the last 6 months with normal hair growth.

DISCUSSION

Azathioprine is an antimetabolite drug having wide range of dermatological indications; of which predominantly listed are vitligo, autoimmune connective tissue disorders(systemic lupus erythematosus and dermatomyositis), photodermatoses, immunobullous disorders, refractory lepra reactions and vasculitides.

Active alopecia areata reveals a perifollicular lymphocytic infiltrate (swarm of bees), which histologically inhibits follicular eruption.[1] Corticosteroids (oral or intralesional form) suppress T-cell-mediated immune response and are frontline agents of therapeutic utility.

Alopecia areata can affect any age group, but it usually follows a chronic relapsing course in children. To obviate unwarranted side effects of long-term steroid use, immunosuppressant of relatively safer therapeutic profile, i.e., azathioprine, is used.

Azathioprine has been used safely in pediatric atopic dermatitis and inflammatory bowel disease for long term.[23] We used minimum dose (1 mg/kg) of azathioprine in all of our patients and discontinued it once hair growth was achieved with maximum duration of up to 6–12 months.

Very few studies employing monotherapy of azathioprine in treatment of refractory and recalcitrant alopecia areata have been reported earlier. Farshi et al.[4] reported a case series of 20 patients of alopecia of which five patients had alopecia universalis, treated with azathioprine with global regrowth percentage of around 53.2%. Vañó-Galván et al.[5] reported efficacy of treatment of azathioprine in recalcitrant cases of alopecia universalis earlier treated with topical and oral corticosteroids.

All the four cases reported in the series were female patients, of which two had multifocal pattern, one had alopecia totalis, and one had alopecia subtotalis. All of them presented with chronic relapsing course with extensive involvement causing considerable psychological distress. All of them responded to short regimens of oral azathioprine, but had to be maintained on the drug for continuing remission. Thiopurine methyltransferase (TPMT)[6] enzyme assay, done usually to assess potential risk of myelosuppression, was not done in any of our patients due to financial constraints. In the absence of TPMT value, patients were kept on minimal dose of azathioprine (1 mg/kg).

All cases were serially monitored down the line during the course of treatment for adverse effects, but no appreciable side effects were documented.

Azathioprine and its analogues interfere with DNA synthesis by inhibition of enzymes of purine synthesis, thereby affecting proliferation of cytotoxic T-cells and also by suppression of cytokines release by helper T-cells which dampens the immune response.

With reduction in colonization of T-cells around follicles, normal follicular growth phase resumes and clinical response is seen in the form of hair growth. Azathioprine scores over other local treatment modalities in that there is no need of infiltration in individual patches (like intralesional corticosteroids), and adverse effects associated with nonspecific immunosuppression caused by long-term systemic steroid administration are also obviated.

However, monitoring of unwarranted side effects of long-term azathioprine accounts for monitoring of hematological parameters, and dipping of leukocyte especially lymphocyte count is considered an alarming feature for stopping the drug. Another limiting factor figured out was to delineate the endpoint of the treatment to maintain the remission.

Newer drugs (Janus kinase inhibitors)[7] are being explored for their role in alopecia areata, but azathioprine still is gaining popularity as a cost-effective alternative.

CONCLUSION

Azathioprine provides a good therapeutic alternative which can be instituted early in therapeutic algorithm for the treatment of alopecia areata considering efficacious results achieving significant and long-term remissions with avoidance of potential adverse effects of conventional immunosuppressive agents, though large-scale studies are warranted.

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

Nil.

Conflicts of interest

There are no conflicts of interest.