Azathioprine: Clinical Indications
Azathioprine is an immunosuppressive agent used to treat a broad spectrum of autoimmune and inflammatory conditions, with licensed indications including systemic lupus erythematosus, dermatomyositis, and pemphigus vulgaris, while serving as a steroid-sparing agent in numerous dermatologic and rheumatologic diseases. 1
Licensed Indications
The following conditions have formal regulatory approval for azathioprine treatment:
- Systemic lupus erythematosus - particularly effective for maintenance therapy in lupus nephritis, showing superiority over cyclophosphamide following induction 1, 2
- Dermatomyositis and polymyositis - functions as a second-line agent in moderate-to-severe refractory disease, with case series demonstrating 57-75% improvement rates 1
- Pemphigus vulgaris - used as a steroid-sparing agent, with evidence supporting greater steroid-sparing effect compared to cyclophosphamide or mycophenolate mofetil 1
- Rheumatoid arthritis - FDA-approved indication with 15% withdrawal rate due to toxicity, comparing favorably to other disease-modifying drugs 3, 4
- Renal transplant rejection prophylaxis - well-established for inhibition of renal homograft rejection 3
Unlicensed Dermatologic Indications
Azathioprine is widely used off-label for numerous skin conditions, with varying levels of evidence:
Strong Evidence (Grade A)
- Atopic dermatitis - recommended as a systemic agent for refractory disease, with RCTs showing 37% improvement versus 20% with placebo after 12 weeks 1
- Chronic actinic dermatitis - supported by double-blind, placebo-controlled trials 1
- Behçet's disease - demonstrated efficacy in placebo-controlled trials 1
Moderate Evidence
- Bullous pemphigoid - used as adjunctive therapy with corticosteroids in 69% of German hospitals, with evidence supporting up to 50% steroid-sparing effect, though combined effectiveness not definitively established 1
- Cutaneous lupus erythematosus - no RCTs available, but case series suggest benefit 1
Limited Evidence (Grade C)
- Psoriasis - may be effective as monotherapy for moderate-to-severe disease, but rarely used in current practice; recent data suggest potential combination with biologics like infliximab 1
Vasculitis and Related Conditions
Azathioprine demonstrates therapeutic efficacy across multiple vasculitic syndromes:
- Wegener's granulomatosis (Granulomatosis with polyangiitis) - RCT evidence shows equivalence to cyclophosphamide for maintaining remission following induction therapy 1
- Cutaneous leucocytoclastic vasculitis - considered for severe cases unresponsive to dapsone, combined with systemic corticosteroids, though evidence limited to case series 1
- Rheumatoid vasculitis - limited evidence supports use 1
- ANCA-associated vasculitis - corresponds to mainstay maintenance therapy 5
Important Caveat
There is insufficient evidence for azathioprine in Henoch-Schönlein purpura nephritis, with no studies addressing whether it affects kidney disease development 1
Other Inflammatory Conditions
Limited formal studies exist, but case series suggest potential efficacy in:
- Pyoderma gangrenosum 1
- Pityriasis rubra pilaris 1
- Lichen planus - anecdotal evidence only (Grade C) 1
- Myasthenia gravis - 83% of tolerant patients improved, with initial response at 4-10 months and peak improvement at 14 months 6
Mechanism of Action
Azathioprine functions as a purine analog that preferentially affects rapidly proliferating cells, particularly B and T lymphocytes during inflammatory states 1, 3. The drug suppresses cell-mediated hypersensitivity and causes variable alterations in antibody production, with cytotoxicity partly due to incorporation of 6-thioguanine nucleotides (6-TGN) into DNA 3. It is considered a slow-acting drug, with effects persisting after discontinuation 3.
Critical Safety Considerations
Absolute Contraindications
- TPMT or NUDT15 deficiency - approximately 0.3% of European/African ancestry patients have absent TPMT activity, risking life-threatening pancytopenia; 2% of East Asian patients have two loss-of-function NUDT15 alleles 7, 3
- Severe infections 7
- Severely impaired hepatic or bone marrow function 7
- Pancreatitis 7
- Hypersensitivity to azathioprine or 6-mercaptopurine 7