Lepr Rev (2007) 78, 290– 292
CASE REPORT
Azathioprine in controlling Type 2 reactions
in leprosy: a case report
S. P. K. ATHREYA*
The Leprosy Mission Hospital, Nand Nagari, Delhi, India
Accepted for publication 10 May 2007
Introduction
Type 2 reaction (Erythema Nodosum Leprosum - ENL), occurs frequently in patients with
lepromatous leprosy.1 Steroids are the treatment of choice but can lead to various
complications when used on a long – term basis.2
In uncontrolled, recurrent Type 2 reactions, several second-line drugs such as clofazimine
or pentoxyfyllin have been tried but not with consistent success.3 Thalidomide, though
effective, is not recommended in some programmes for pre-menopausal female patients due
its teratogenic effects. The search for an effective alternative led to azathioprine known for its
suppressive action on T-cells and antibody mediated cytotoxicity.4
We present a case report of a female leprosy patient where azathioprine was used
successfully in combination with cortico-steroids to control Type 2 reaction.
Case Report
A 53 year old female diagnosed elsewhere in May 2000 as lepromatous leprosy presented at
our hospital in September 2000 with a 2-month history of papulonodular eruptions associated
with general malaise and recurrent fever. She was diagnosed with a Type 2 reaction.
Histopathology confirmed the diagnosis of BL leprosy, and her bacteriological index was
3·3 þ . She reported that she had taken two pulses of MDT and was prescribed non-steroidal
anti-inflammatory (NSAID) for her symptoms of pain and fever. She gave no history of
diabetes mellitus, hypertension, tuberculosis or drug intake for reason other than for the
current problem.
She was febrile, moderately built, well nourished, with no visible abnormality or
significant lymphadenopathy, hepatosplenomegaly or skeletal defects. The skin was
diffusely infiltrated, studded with tender papules and nodules distributed over her face and
Correspondence to: S. P. K. Athreya, The Leprosy Mission Hospital, Nandnagri, Delhi 110 093, India (Tel: þ 91
11 22581451; Fax: þ 91 11 22110788; e-mail: [email protected])
0305-7518//064053+03 $1.00
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Azathioprine in controlling Type 2 reactions
291
upper limbs. Laboratory investigations were normal except for a slight increase in ESR
and white blood cell count. On examination her ulnar and lateral popliteal nerves were
found to be thickened bilaterally but with no pain or tenderness. There was no sensory or
motor impairment.
She continued MB-MDT along with 40 mg prednisolone daily for treatment of ENL
reaction, following standard regimen. A time-line showing the laboratory investigations,
superimposed morbidity and treatment given is shown in Figure 1.
Azathioprine 50 mg/day was prescribed from August 2002 together with prednisolone
35 mg and clofazimine 300 mg daily. After one more episode in September 2002, the ENL
never recurred, and from June 2003, all drugs were stopped. Overall, she had consumed
nearly 20 g of prednisolone, 46 cc of dexamethasone and 11 g of azathioprine.
Fortnightly review till the end of 2004 revealed no further evidence of nerve function
impairment, and her full blood counts were normal indicating good bone marrow function.
She complained of weakness and loss of appetite in June 2003, but no abnormalities were
found on investigation. Body weakness is not a recognised side-effect of azathioprine but
anorexia is. She continued attending the hospital with complaints of body weakness and loss
of appetite associated with urinary tract infection, and minor gynecological problems. In
March 2004 she attended with knee joint pain that subsided in a week after treatment with
NSAIDs.
Figure 1. Timeline showing laboratory investigation, superimposed morbidity and treatment given.
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S.P.K. Athreya
Discussion
Type 2 reactions can be chronic, debilitating and unsuccessfully treated even with massive
dosages of steroids.1,2 Marlowe et al reported a successful use of azathioprine in treatment of
Type 1 reactions.5 The efficacy of azathioprine in Type 2 reactions is yet to be determined
through appropriate randomised controlled trials (RCT). In our patient, azathioprine was
introduced only after intensive treatment with steroids for nearly 2 years had failed to control
the Type 2 reaction. The dose of azathioprine was kept low since immune suppression may
have been already achieved with steroids.
Our experience shows that azathioprine may be useful in treating recurrent chronic ENL.
This case report highlights the need for larger studies defining the role of azathioprine in
managing Type 2 reactions.
Acknowledgements
I would like to thank Dr. P.S.S. Rao, Research Coordinator, for guidance while writing this
case report, and Dr. D. Vijay Kumar, Superintendent, TLM Hospital Nand Nagri, for support,
and to Mr. Jeyakumar Daniel, Director, for encouragement.
References
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2
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4
5
Pfaltzgraff RE and Ramu G. Clinical leprosy, Chap 17. In: Hastings RC (ed). Leprosy, 2nd edn. Churchill
Livingstone, London, 1990.
Lockwood DNJ. Leprosy, Chap 29, Page 29.1–29.21. In: Burns T, Breathnach S, Cox N, and Griffiths C (eds).
Vol.2, 7th edn. Rook’s Textbook of Dermatology, 7th edn. Blackwell Publishing, 2004.
De Carsalade GY, Achirafi A, Flageul B. Pentoxyfylline in the treatment of Erythema nodosum leprosum: results
of an open study. Acta Leprologica, 2003-4; 12: 107 –128.
Polifka JE, Friedman JM. Teratogen update: azathioprine and 6-mercaptopurine. Teratology, 2002; 65: 240– 261.
Marlowe SN, Hawksworth RA, Butlin CR, Nicholls PG, Lockwood DNJ. Clinical outcomes in a randomized
controlled study comparing azathioprine and prednisolone versus prednisolone alone in the treatment of severe
leprosy type 1 reactions in Nepal. Trans., R Soc Trop Med Hyg, 2004; 10: 602 –609.