A 41-year-old male, previously well, presented with a 2-year history of progressively worsening constitutional symptoms (fever, weight loss, and night sweats) and a dry cough. Additionally, he noted progressively worsening chronic lower back pain without sensory or motor fallout and a painful nonhealing ulcer on his right hallux. During this period, he presented several times to his local primary health care clinic where he was tested twice for MTB with a sputum Gene Xpert (GXP) test, which were both negative. He received symptomatic treatment for his back pain with paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), and antibacterial cream for the ulcer on his toe.
His first contact with our institute was via the vascular surgery outpatient clinic, where he was referred for the nonhealing ulcer on his right hallux (Figure 1(a)).  Table 1 reveals the blood investigations. The inflammatory markers were markedly elevated (erythrocyte sediment rate >130 mm/hr (normal range: less than 20 mm/hr) and C-reactive protein 113 mg/ml (normal range: less than 10 mg/ml)). Immunoglobulin A (IgA) levels were raised at 6.2 g/L (normal range: 0.7-4 g/L), measurement of circulating IgA-MTB antigen complexes was not available at our laboratory. There was a mildly raised anti-DNase B of 259 IU/ml (normal range: less than 200 IU/ml), with a negative autoimmune antibody panel (antinuclear antibodies, antidouble-stranded DNA antibody, and antineutrophil cytoplasmic antibodies). Testing for human immune virus (HIV), hepatitis B and C virus and syphilis were all negative. A nephrology consult was requested for a raised urine protein-creatinine ratio (uPCR) of 0.242 g/mmol creatinine.
A clinical examination found him to be normotensive, apyretic, and cachectic with no peripheral lymphadenopathy nor oedema. Tenderness upon palpation of his thoracic spine was noted with no associated neurological fallout. On dipsticks, he had 3+ leucocytes and 3+ red blood cells, while urine microscopy revealed granular casts with no bacterial culture growth.  Figure 1(b) shows a chest radiograph demonstrating bilateral reticular-nodular opacities.
An intensive MTB work up was performed. This included an induced sputum which tested trace positive for MTB on GXP and subsequently cultured MTB, sensitive to rifampicin and isoniazid. A biopsy of the right hallux ulcer (Figure 1(a)) revealed necrotising granulomatous inflammation with a solitary acid-fast bacillus seen on microscopy. Magnetic resonance imaging (MRI) of his spine (Figure 1(c)) revealed multi-level contiguous spondylitis at levels T6 to T10 with discitis and an epidural and paraspinal collection complicated by spinal cord compression but no oedema, in keeping with spinal MTB. No urine GXP nor urine TB cultures were sent.
The ultrasound showed bilateral normal-sized kidneys with increased echogenicity. A kidney biopsy was performed. The differential prior to kidney biopsy was acute interstitial nephritis (AIN) secondary to NSAIDs, direct infection of the kidney by MTB, or postinfectious glomerulonephritis.
Kidney biopsy demonstrated a total of 59 glomeruli, four of which were globally sclerosed, three were segmentally sclerosed, and one showed a cellular crescent to be present. Haematoxylin and eosin (H&E) showed glomeruli with diffuse mesangial hypercellularity with no evidence of endocapillary hypercellularity (Figure 2(a) and 2(b)). The Jones methenamine silver stain revealed no double contours or spikes present, and the Congo Red did not show any evidence of amyloidosis. Immunohistochemical stains revealed diffuse strong IgA (3+) staining within the mesangium with lesser amounts noted within the paramesangium region (Figure 2(c) and 2(d)). Weak staining for IgM and C3 were noted (1+ intensity). IgG and C1q stains were negative. The background kidney showed mild tubular atrophy and interstitial fibrosis with a chronicity score of 2/10 (mild) as per Sethi et al. criteria. No granulomata nor acid-fast bacilli were seen and no MTB were cultured. The diagnosis of IgAN (M0E0S0T0-C1) was assessed in the setting of disseminated MTB (pulmonary, spinal and skin). Early secreted antigenic target-6 staining was not available at our laboratory.
A multidisciplinary consultation (nephrology, orthopaedics, infectious diseases, and dermatology) advised first line MTB treatment with an extended course of 12 months (2 months intensive phase - (rifampicin/isoniazid, pyrazinamide/ethambutol), followed by 10 months of continuation phase (rifampicin/isoniazid)). An angiotensin-converting-enzyme inhibitor (enalapril) was prescribed for the proteinuria. At four months follow-up, the patient reported marked improvement in constitutional symptoms and back pain, while estimated GFR increased and uPCR also improved (Table 1).