Comparison of outcomes of azathioprine, leflunomide and allergen avoidance in patients with patch test-positive pigmented contact dermatitis: a randomized comparative study

Clin Exp Dermatol. 2024 Feb 14;49(3):247-254. doi: 10.1093/ced/llad378.


Background: Pigmented contact dermatitis (PCD) is a noneczematous form of allergic contact dermatitis characterized by dermal hyperpigmentation. Allergen avoidance is the cornerstone of therapy, but it is difficult to achieve. The use of immunosuppressives seems rational, but data are lacking.

Objectives: To compare outcomes with azathioprine (AZA), leflunomide and allergen avoidance (AA) in patients with PCD.

Methods: A comparative study was conducted on 28 patients with patch test-positive PCD who were randomly allocated to one of three treatment groups: AZA 2 mg kg-1 daily for 24 weeks + AA (n = 10); leflunomide (LEF) 20 mg daily for 24 weeks + -AA (n = 8); AA alone (n = 10). Patients were followed up for an additional 24 weeks. The Dermal Pigmentation Area and Severity Index (DPASI) score and Hindi Melasma Quality of Life scale (MELASQOL) were used to assess hyperpigmentation and quality of life (QoL). respectively.

Results: Hair colorants (n = 12) and paraphenylenediamine (n = 8) were the most common allergens. Mean (SD) DPASI score decreased from 30.97 (3.69), 32.35 (3.90) and 31.86 (3.47) to 13.78 (4.25), 21.67 (2.99) and 20.64 (3.82) at 48 weeks in the three groups, respectively (P < 0.001); the maximum percentage decline was seen with AZA (56%). Mean (SD) MELASQOL score was reduced in the three treatment groups from 48.0 (6.46), 46.75 (3.69) and 46.6 (4.65) to 19.6 (6.98), 24.5 (5.80) and 24.0 (5.49), respectively, at 48 weeks (P < 0.001). Reductions in DPASI and Hindi MELASQOL scores were significantly correlated. The most frequent adverse event was transaminitis in both the AZA and LEF groups.

Conclusions: Patients on AZA achieved a statistically significantly greater reduction in DPASI and MELASQOL score; therefore, AZA may fulfil an unmet need in PCD treatment. An objective reduction in hyperpigmentation was paralleled by an improvement in QoL score, reiterating the need for active management of this disease.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Allergens
  • Azathioprine / adverse effects
  • Dermatitis, Allergic Contact* / diagnosis
  • Dermatitis, Allergic Contact* / etiology
  • Humans
  • Leflunomide / adverse effects
  • Melanosis*
  • Patch Tests
  • Quality of Life


  • Allergens
  • Azathioprine
  • Leflunomide