Thyroid Research and Practice

: 2015  |  Volume : 12  |  Issue : 2  |  Page : 71--73

Life threatening ANCA associated vasculitis on Carbimazole exposure

Vimal Upreti1, Shrikant Somani1, Narendra Kotwal1, DS Bhakuni2,  
1 Department of Endocrinology, Army Hospital, Delhi Cantt, India
2 Department of Rheumatology, Army Hospital, Delhi Cantt, India

Correspondence Address:
Vimal Upreti
Department of Endocrinology, Army Hospital, Delhi Cantt 110 010


ANCA-associated vasculitis is a rare side effect of commonly used thionamide group of anti-thyroid drugs. It is most commonly associated with use of propylthiouracil and p-ANCA positivity. However, rarely it has been reported with carbimazole exposure and c-ANCA positivity. Here we report a case of life-threatening episode of c-ANCA-associated vasculitis in a female patient of Graves«SQ» disease on exposure to carbimazole, who was managed successfully by discontinuation of carbimazole and immunosuppressive therapy. A high index of suspicion is required for diagnosing such cases, who if not diagnosed correctly, may have adverse outcome.

How to cite this article:
Upreti V, Somani S, Kotwal N, Bhakuni D S. Life threatening ANCA associated vasculitis on Carbimazole exposure.Thyroid Res Pract 2015;12:71-73

How to cite this URL:
Upreti V, Somani S, Kotwal N, Bhakuni D S. Life threatening ANCA associated vasculitis on Carbimazole exposure. Thyroid Res Pract [serial online] 2015 [cited 2019 Sep 20 ];12:71-73
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Full Text


Thionamides group of anti-thyroid drugs(ATDs) including carbimazole, methimazole, and propylthiouracil (PTU) are commonly used in treatment of hyperthyroidism in India. Their common side effects include skin rash, arthralgia, urticaria, serum sickness, and raised transaminases. Drug-induced ANCA-positive vasculitis is uncommon but potentially life-threatening complication associated with use of ATDs, most frequently (>90%) occurring in association with propylthiouracil (PTU). [ 1],[2] ANCA associated vasculitis following use of carbimazole has been described rarely; only in the form of isolated case reports. [3],[4],[5] Here we report a case of severe ANCA-positive vasculitis unmasked by use of carbimazole in a female patient.


A 48-year-old female presented to local physician in August 2013 with complaints of tremulousness of hands, palpitations, excessive sweating, and weight loss (14 kg) over a period of 3 months. Clinically, she had a goiter, stare with overt features of hyperthyroidism. Thyroid profile was consistent with thyrotoxicosis [T3-2.6 ng/ml (0.7-2); T4-16 ug/dl (5.5-12.5); TSH - 0.02 uIU/ml (0.35-0.5)], anti-TPO antibody was positive and rest of the hemogram and biochemistry were within normal limits. She was prescribed oral carbimazole 40 mg daily with beta-blockers. Two months later, she complained of generalized weakness and passage of black tarry stools. Evaluation showed anemia (Hb - 4 gm%) with normal total leucocyte count (8,699/cmm) and platelet count (2,10,000/cmm). Coagulation profile including PT (Control/Test - 12/14 s, INR 1.12) and aPTT (Control/Test - 35/33 s) was normal. Upper gastrointestinal endoscopy revealed a bleeding solitary gastric ulcer. Rest of the relevant investigations were normal. She was managed with 6 packed RBC infusion, proton pump inhibitors (PPI), and endotherapy of the ulcer. With this therapy, melena stopped, Hb improved to 10.4 g/dl and she was discharged on hematinics, PPI, and carbimazole. Another 3 months later, she presented with complaints of generalized weakness, myalgia, arthralgia, easy fatigability, cough with reddish expectoration, worsening dyspnea and rash all over body (extremities > trunk). She also gave history of intermittent episodes of melena over past 3 months. Clinically, she had tachypnea (Respiratory rate - 26/min), tachycardia (PR - 130/min), normal JVP, pallor, 3-4 mm sized palpable non-blanchable rash over both the legs, arms and trunk [Figure 1], diffuse fine crackles in all the lung fields, and features of thyrotoxicosis. Rest of systemic examination was normal.{Figure 1}

Past history was significant with complaints of recurrent episodes of arthralgia and painful red eye for past 8 years, for which she was prescribed topical steroids by ophthalmologist.

Investigations revealed low Hb (4.4 g/dl), polymorphonuclear leucocytosis (TLC - 15,700/cmm, neutrophils 80%), normal platelet count (4.52 lac/cmm), and elevated ESR (80 mm in 1 st hour). Evaluation of anemia revealed it to be due to iron deficiency (microcytic hypochromic picture in peripheral smear; total iron - 19 μg/dl (normal: 60-160), TIBC - 1231 μg/dl (normal: 250-380) and Ferritin - 285 ng/ml (normal: 10-150). She also had hypoalbuminemia (serum albumin - 2.4 g/dl; normal: 3.5-5.5). Rest of the biochemistry profile was normal. Radiograph of chest revealed non-homogenous opacities throughout both the lung fields [Figure 2]a] and CECT chest/abdomen/pelvis revealed bilateral ground glass opacities and air space consolidation with diffuse lymphadenopathy [Figure 2]b]. Fibreoptic bronchoscopy revealed hemorrhagic BAL aspirate. Stool examination was positive for occult blood and UGI endoscopy showed Mallory Weiss tear. Other investigations including infection screen, urine analysis, and bone marrow biopsy were normal.

Biopsy from skin lesion was suggestive of small vessel vasculitis. Vasculitis profile showed strongly positive c-ANCA-PR3 (>100 U/ml; normal: <3.5) and negative p-ANCA-MPO (1.59 U/ml; normal: <9). Her thyroid profile was as follows: T3-2.68 ng/ml (0.8-2.1), T4-16.24 ug/dl (5.5-13.5), TSH - 0.1 uIU/ml (0.5-6.5).{Figure 2}

In view of above findings, she was diagnosed with Graves' disease (GD) with persistent thyrotoxicosis with active small vessel vasculitis resulting in diffuse alveolar hemorrhage. Carbimazole was immediately stopped and rheumatology consult was taken. A diagnosis of granulomatosis with polyangiitis was made, and she was started on oral prednisolone 1 mg/kg body weight with cyclophosphamide pulse therapy as remission induction regime along with other supportive therapy. She recovered gradually with above measures, was radioablated with 10 mCi of I-131 and was exhibited 6 cycles of cyclophosphamide along with maintenance dose of prednisolone.

Inadvertently, oral carbimazole was restarted by treating nuclear medicine physician, to which she developed purpuric skin rash within 4 days that disappeared immediately after stopping carbimazole. She was counseled never to restart carbimazole and same was clearly documented. At 6 months of follow up, she has gained about 12 kg weight, is asymptomatic, and euthyroid.


Drug-induced vasculitis is a rare side effect of the thionamide group of ATDs with only about 100 cases reported till date. [2] Owing to limited physician awareness, delay in diagnosis is common as in our case. Presenting symptoms are heterogenous and include renal involvement (67%), arthralgia (48%), fever (37%), skin involvement (30%), respiratory tract involvement (27%), myalgia (22%), scleritis (15%), and other manifestations (18%). [3] Our patient too, presented with skin rash and pulmonary manifestations and had past history of arthralgia and red eye. It is usually seen in females (75%), with PTU use (90%) and those who have received long-term (>18 months) ATDs or who have been recently started on ATDs. [1] However, cases such as ours developing vasculitis with carbimazole exposure have been rarely reported. [3],[4],[5] Our patient might have developed ANCA positivity while on carbimazole or it could have been precipitated by its exposure, since she had a past history of arthritis and red eye. p-ANCA (MPO) positivity is seen in 7.1-15.9% patients of GD treated with carbimazole [6],[7] while c-ANCA (PR3) positivity is described in case reports only. [5],[6] Proposed mechanisms of drug-induced vasculitis include modification of the offending drug that accumulates in neutrophils by MPO and PR3 or modification of MPO and PR3 by the offending drug, rendering them antigenic and subsequently inciting B-cell response in the form of production of ANCA. [2] Treatment includes withdrawal of the offending drug and immunomodulatory therapy in organ-threatening cases, [4],[5] as was done in our patient.

Treating physicians should be aware of this potential life-threatening vasculitis caused or precipitated by carbimazole and importance of adequate documentation in medical records to prevent inadvertent re-challenge cannot be overemphasized.


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