Title : Multisystem IgG4-related disease with cardiac involvement mimicking cardiac sarcoidosis: a diagnostic challenge background
Abstract:
Background
IgG4-related disease (IgG4-RD) and sarcoidosis are multisystem inflammatory disorders with some overlapping clinical, radiological, and histopathological features. Both may involve the orbit, salivary glands, lymph nodes, and cardiovascular system, and may present with constitutional symptoms. Cardiac involvement is well recognised in sarcoidosis and increasingly reported in IgG4-RD, but myocardial disease in IgG4-RD remains rare and poses significant diagnostic challenges, particularly as imaging findings can be similar to Sarcoidosis. We present an interesting case where the differentiation between IgG4-RD and sarcoidosis was challenging, including clinical features, imaging and histology slides.
Case presentation
A 57-year-old man presented with a two-year history of progressive bilateral eye redness, proptosis, altered colour perception, and night sweats, without diplopia or pain. Examination demonstrated bilateral proptosis, reduced ocular motility, non-tender superolateral orbital masses, lower lid retraction, and parotid and submandibular gland enlargement. MRI of the orbits showed bilateral lacrimal gland enlargement consistent with inflammatory or lymphoproliferative disease. Laboratory investigations revealed marked hypergammaglobulinaemia (IgG 26.5 g/L) with significantly elevated IgG4 (11.44 g/L), low IgM, raised ESR and CRP, and negative ANA and ANCA. Lacrimal gland biopsy demonstrated a dense lymphoplasmacytic infiltrate with >80% IgG4-positive plasma cells, confirming IgG4-RD. The disease progressed to involve salivary glands with xerostomia, nasal obstruction, and gingival swelling. Whole-body PET-CT revealed widespread FDG-avid lymphadenopathy, bilateral lacrimal and parotid involvement, myocardial uptake, and a periaortic soft tissue cuff.
Cardiac assessment showed first-degree atrioventricular block (P-R interval 266ms) and right bundle branch block (QRS duration 141ms) on ECG, with markedly elevated NT-proBNP (3928 pg/mL). Transthoracic Echocardiography demonstrated concentric left ventricular hypertrophy with systolic and diastolic dysfunction, left atrial dilation, and features of pulmonary hypertension. Cardiac MRI revealed multifocal late gadolinium enhancement and myocardial oedema, appearances considered typical of cardiac sarcoidosis, and serum ACE was found to be elevated at 145U/L. However, EBUS-guided lymph node sampling, endomyocardial biopsy, and salivary gland cytology were non-diagnostic for sarcoidosis. Further evaluation with carbohydrate-depleted, fasting, half body cardiac 18-FDG PET CT confirmed left ventricular dysfunction (EF 42%), areas of scarring, and low-grade metabolic activity consistent with an inflammatory, infiltrative process. Following multidisciplinary discussion, the overall clinicopathological features supported IgG4-RD with probable cardiac involvement, and treatment was planned accordingly.
Discussion:
This case shows that IgG4-RD and sarcoidosis can be clinically and radiologically indistinguishable, particularly with cardiac involvement. Biomarkers such as ACE and IgG4 should be interpreted cautiously, multimodality imaging may be discordant, and negative biopsies do not exclude disease because of sampling limitations. Multidisciplinary discussion is essential when diagnostic uncertainty affects immunosuppression and the timing of device therapy.
Learning points for clinical practice
- IgG4-RD may closely mimic sarcoidosis, including cardiac imaging appearances.
- Elevated IgG4 with supportive histopathology outweighs non-specific biomarkers such as ACE.
- Cardiac involvement should be considered in multisystem IgG4-RD.
- Multidisciplinary evaluation is essential when diagnostic uncertainty influences immunosuppressive strategy.
