Case Presentation: A previously healthy 45-year-old male, who recently immigrated from India, presented with worsening dyspnea at rest, epistaxis, hearing loss, and bilateral eye irritation after three weeks on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy. Negative Mycobacterium tuberculosis polymerase chain reaction (MTB PCR) and acid-fast bacillus (AFB) sputum culture results from the previous admission to a satellite hospital, along with abnormal liver chemistries at the current admission, prompted the discontinuation of RIPE therapy. Chest computed tomography redemonstrated cavitary lesions with interval enlargement. Further examination revealed nasal septal perforations, bilateral tympanic membrane perforations, and subretinal/choroidal lesions. During admission, palpable purpura erupted in bilateral lower extremities, which demonstrated findings consistent with small-vessel vasculitis per pathology. Serum cytoplasmic-antineutrophil cytoplasmic antibodies (c-ANCA) was positive (1:80), and serine proteinase-3 (PR3) IgG was 546 AU/mL (ref < 19 AU/mL). Bronchoalveolar lavage samples produced a negative MTB PCR test and AFB culture. Treatment was initiated for granulomatosis with polyangiitis (GPA) with intravenous methylprednisolone and rituximab, and the patient was discharged with outpatient follow-up.
Discussion: Cavitary lung lesions with accompanying respiratory symptoms offer a broad differential diagnosis, including etiologies with potentially competing therapeutics. For a 45-year-old male who recently immigrated from India, a high suspicion for tuberculosis (TB) was reasonable considering the high incidence of TB in India (27% of new cases worldwide in 2022) [1] and occurrence of cavitary lung lesions in 40–87% of pulmonary TB cases [2]. Nevertheless, symptomatic progression despite RIPE therapy and a previously negative TB work-up led to repeat testing, including autoimmune and infectious evaluations. Specifically, ANCA testing has a sensitivity of 92% for patients with active limited-to-severe GPA [3], and PR3-ANCA titers (≥ 65 AU/mL) can then help differentiate GPA from non-ANCA associated vasculitides [4]. However, in an actively deteriorating patient without laboratory results to differentiate GPA from concomitant TB, the treatment decision can be challenging. The initiation of RIPE therapy for presumed TB and its associated liver dysfunction further complicated the diagnosis, emphasizing the risks of misdiagnosis and unnecessary therapy. In specific clinical scenarios, corticosteroids have been shown to mildly improve outcomes in active pulmonary and extrapulmonary TB infections [5,6,7] and not impair outcomes in concomitant TB and GPA cases [8,9]. A meta-analysis found corticosteroids improved outcomes of pulmonary TB at one month (risk ratio: 1.16) [5]. Interestingly, in vitro studies have shown dexamethasone to abrogate TB-induced mitochondrial signaling that typically results in cell necrosis [10].
Conclusions: Despite insufficient evidence that corticosteroids benefit TB outcomes, studies suggest low-risk of harm to initiate GPA treatment with possible concomitant TB. We hope this case informs providers to avoid diagnostic bias and consider early steroid treatment for patients suspected of GPA in the absence of an unequivocal TB diagnosis.