A 66-year-old lady presented with three-week history of night sweats, low-grade pyrexia and weight loss. She also had progressive dyspnoea on exertion over 3-4 weeks and non-productive cough that failed to respond to a seven-day course of oral amoxicillin. Her medical history included well controlled asthma, migraine, hypothyroidism and a tonsillectomy as child, with no hospitalisations. She is a non-smoker with minimal alcohol consumption, and no recent travel abroad. On examination she had a low grade pyrexia (37.9  C). Respiratory examination revealed respiratory rate of 24 breaths/min; oxygen saturations were 97% on air. There were minimal coarse crackles in the right lung base and subclavian lymphadenopathy. Cardiovascular, abdominal and neurological examinations were unremarkable. Rectal examination showed no evidence of melena.
Full blood count revealed normocytic anaemia with a haemoglobin of 70 g/L (baseline haemoglobin 136 g/L), white cell count of 17.3 x 109/L (Neutrophil counts 14.7 x 109/L) and mildly raised C-reactive protein (74 mg/L). Platelet counts was also elevated (667 x 109/L). Erythrocyte sedimentation rate (ESR) was markedly elevated at 114 mm/hr. Her bilirubin was also slightly raised (29 mumol/L) with a low albumin (28 g/L), liver and renal function tests were otherwise unremarkable. A chest radiograph showed bilateral small pleural effusion.
In light of the persistent cough, night sweats, weight loss and significantly raised ESR > 100mm/hr, initial differential diagnosis included infective (e.g. tuberculosis), inflammatory (e.g. polymyalgia rheumatica, rheumatoid arthritis) and malignant (e.g. lymphoma, multiple myeloma) aetiology.
CT scan showed extensive mediastinal lymphadenopathy, with the largest lymph node seen in the paratracheal region measuring 22 mm and additionally in the subclavian, pretracheal and paratracheal distribution (Fig. 1). No pulmonary masses were found. Broncho-alveolar lavage showed no acid-fast bacilli on smear, and no growth after 6 weeks of culture. No malignant cells were detected on cytology. Myeloma screen was negative with normal serum immunoglobulins and absence of Bence Jones protein in urinalysis. Serum calcium was also within normal range (2.13 mmol/L).
A haemolysis screen revealed raised lactate dehydrogenase (643 IU/L) and reticulocytes (9%, absolute count 292 x 109/L). Iron, folate and Vitamin B12 level and thyroid function test were all within normal range. Direct antiglobulin test (DAT) was positive for complement C3d, and negative for IgG, consistent with cold agglutinin haemolysis. Blood film confirmed multiple cold agglutinins, large platelets and target cells. Serology showed positive IgM for Mycoplasma pneumonia, and there was >4 fold increase in IgG between the initial sample and convalescent sample.
The patient was initially treated with intravenous (IV) fluids and empirical broad-spectrum IV pipercillin-tazobactam as well as oral clarithromycin for the atypical presentation. Given her symptomatic anaemia, two units of warm packed red cells was transfused. Her observations post-transfusion remained stable, apyrexial with no further significant haemolysis, and she was discharged with oral clarithromycin.
The patient was followed up in respiratory clinic one month following hospitalisation, and found to have a normal clinical examination. Interval CT scan showed improving but persistent lymphadenopathy (Fig. 1). Endobronchial ultrasound (EBUS) was therefore performed for mediastinal lymph node biopsy, which showed fragments of blood clots with lymphocytes/anthracotic lymphoid tissue. No malignant cells were seen. The patient remained symptom-free in two month follow up.