Hypothyroidism as a late manifestation of drug hypersensitivity syndrome.

Sir,

A sixteen year-old girl presented with a history of swelling of the face and extremities, dryness of the skin, slurring of speech, and weight gain of one month's duration. Five months ago, she was admitted to our hospital for fever and skin rash which started four weeks after taking leflunomide tablets for joint pain. She had eosinophilia and abnormal liver function test results. She was diagnosed to have drug hypersensitivity syndrome (DHS) to leflunomide and was treated with oral steroids. She recovered completely and all the medications were stopped. Examination revealed that she had puffiness of the face, nonpitting edema, and dry skin. Beau's lines were present on the nails of her fingers and toes. Deep tendon reflexes were sluggish but her routine hemogram and urinalysis results were normal. Thyroid function tests showed T3: 0.32 ng/mL, T4: 0.8 μg/mL and TSH:142 μIU/mL (normal T3: 0.60–1.81 ng/mL, T4: 4.5–10.9 μg/mL, TSH: 0.35–5.5 μIU/mL) which was suggestive of hypothyroidism. Her symptoms subsided after treatment with L-thyroxine 100 μg tablets per day.

Drug hypersensitivity syndrome (DHS) is a severe, multisystem, adverse drug reaction that may occur following the use of numerous medications, including anticonvulsants, sulfonamides, and leflunomide.[1] This idiosyncratic reaction is characterized by fever, skin rash, and internal organ involvement.[2] It is associated with considerable morbidity and mortality. Various internal organs and systems like the liver, CNS, kidney, and hematological system may be involved; asymptomatic involvement of many organs is also likely.[3] A small group of patients may develop hypothyroidism as a part of autoimmune thyroiditis within two months of onset of symptoms of DHS. These patients may present with signs of hyperthyroidism at the time of DHS which will be often missed so that this group of patients presents with hypothyroidism several months after the acute episode.[3] Brown et al. reported minocycline-induced DHS associated with multiple autoimmune complications, including thyroid disease, type 1 diabetes mellitus, and elevated markers of systemic autoimmunity.[4]

Leflunomide is a new immunomodulator drug used in the management of rheumatoid arthritis and is known to cause severe, even fatal, adverse reactions.[1] Our patient initially presented with features of DHS to leflunomide and developed signs and symptoms of hypothyroidism after five months. To the best of our knowledge, this is the first report of hypothyroidism as a late consequence of DHS in Indian literature. In conclusion, it is advisable to screen for thyroid functions during the acute phase and during subsequent follow-up in all patients with DHS.