Necrotizing Gingivitis: A Possible Oral Manifestation of TiclopidineInduced Agranulocytosis(Journal of the New Zealand Medical Association, 15-June-2007, Vol 120 No 1256 Rama Krsna Rajandram, Roszalina Ramli, Fadzlina Karim, Roslan Abdul Rahman, Leong Chooi Fun)

Ines Augustina Sumbayak 0806324974

ABSTRACT Case: A 54-year-old Malaysian-Chinese female of ticlopidine-induced agranulocytosis and neutropenia with necrotizing gingivitis. Started on ticlopidine 250 mg twice daily 3 weeks prior to this hospital admission. Treatment: Intravenous metronidazole and amoxicillin and clavulanic acid (Augmentin) and concurrently stopped ticlopidine. Result: Necrotizing gingivitis possibly secondary to agranulocytosis was made. The patient was discharged home after 2 weeks of hospitalisation.

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INTRODUCTION Necrotizing gingivitis (NG) is an acute opportunistic infection of the gingiva. Treponema spp, Selenomonas spp, Prevotella intermedia, Borrelias, Gram-positive cocci, beta-haemolytic group B streptococci, and Candida albicans were all shown as significant bacteria in the pathogenesis of this condition.

Agranulocytosis is a rare haematological condition defined as profound decrease in the number of neutrophils in the circulating blood i.e. less than 0.5 109/L and it can be a serious and life-threatening side effect of ticlopidine. An unusual case of NG which may be secondary to agranulocystosis induced by ticlopidine.

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CASE REPORT A 54-year-old Malaysian-Chinese female was referred to the Oral and Maxillofacial Surgery Clinic: generalised gingival and teeth pain associated with recurrent fever, difficulty in swallowing, and reduced appetite for 1 week. Diagnosis: acute necrotizing gingivitis very inflamed gingiva with ulcers particularly on the papilla.

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Past medical history: sick sinus syndrome cardiac pacemaker inserted 4 months. Also previously diagnosed with hypertension, bilateral knee osteoarthritis, gastritis, and hepatitis B. She was on verapamil 40 mg three times daily for the past 7 years and ticlopidine (Ticlid) 250 mg twice daily which was started about 3 weeks prior to this admission. Full blood count: white cell count of 0.6 109/L neutrophils 0.1 109/L lymphocytes 0.4 109/L Hb 7.4 g/dL hypochromic microcytic anaemia platelet declined from 154 to 22 109/L C-reactive protein and ESR were increased to 27.55 mg/L and 123 mm/hour procalcitonin 0.68425

Bone marrow showed an increase in plasma cells with some showing flame-shaped, binuclearity, occasional plasmablast, and severe suppression of granulopoiesis, which was suggestive of multiple myeloma. A full work-upincluding serum immunoglobulin, skeletal survey, serum calcium, serum protein electrophoresis and urine protein electrophoresiswas performed.

Hypochromic anisopoikilocytosis with the presence of pencil cells

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Started on intravenous amoxicillin and clavulanic acid (Augmentin) 1.2 g and metronidazole (Flagyl) 500 mg, also advised to use Chlorhexidine mouthwash (0.12%) After two weeks of hospitalisation: total white cell count 5.6 109/L neutrophils 2.4 109/L lymphocytes 2.2 109/L haemoglobin 10.4 g/dL platelets 170 109/L

She was discharged well and during her follow-up about 3 months later, her full blood count had normalised periodontal therapy commenced.7

DISCUSSION Ticlopidine is a potent and long-acting inhibitor of platelet aggregation and has been shown to be more effective than aspirin in preventing recurrent transient ischaemic attacks. Side effects: max risk of the onset of haematologic dyscrasia is from 3 weeks to 3 months after starting therapy agranulocytosis, aplastic anaemia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura. Pathogenesis: unclear. Ticlopidine exerts a dosedependent direct cytotoxic effect on myeloid precursors in bone marrow cultures, which may be due to local increases in prostaglandin E2 or genetic predisposition.

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Other oropharyngeal side effect: - White cell disorders mouth ulcers and pharyngitis - Iron deficiency anaemia disrupt the oral mucosal surface integrity: ulcers, glossitis, angular cheilitis Apart from the orophrayngeal side effects, skin rashes has also been reported in a study.

CONCLUSSION !!! The possible association of Necrotizing Gingivitis and Agranulocytosis in a patient who is taking ticlopidine. Stopped ticlodipine and started vigorous antibiotics treatment improved the patients condition.

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