Not Vasculitis, But a Bacterium: Proteus-induced Diffuse Alveolar Hemorrhage

Sir, Diffuse alveolar hemorrhage (DAH) is a clinical syndrome marked by bleeding within the alveolar spaces, typically caused by damage to the alveolar–capillary membrane. Histopathologically, DAH manifests in one of three patterns: pulmonary capillaritis, bland pulmonary hemorrhage, or diffuse alveolar damage. Of the three patterns, pulmonary capillaritis is the most prevalent and is frequently associated with autoimmune diseases.[1] Infectious etiologies are a less common cause of DAH. The pathogens most frequently associated with DAH in immunocompetent individuals include influenza A (H1N1), dengue virus, Leptospira spp., Plasmodium spp., and Staphylococcus aureus.[2] We report a successfully managed case of infective DAH. The clinical relevance of this case lies in the identification of the causative pathogen, the timely therapeutic intervention, and the diagnostic utility of molecular testing – factors that underscore its significance and contribute to the growing recognition of infectious DAH. A 49-year-old male with no known comorbidities presented with a 3-day history of high-grade, intermittent fever accompanied by chills, rigors, headache, myalgia, and a nonproductive cough. Notably, there was no history of hemoptysis. His vitals were stable on presentation. Bronchial breath sounds were noted over the right suprascapular, supraclavicular, and infraclavicular regions. Radiographic imaging demonstrated nonhomogeneous perihilar opacities involving the right upper and middle lung zones. Laboratory evaluation revealed a hemoglobin concentration of 14.4 g/dL, total leukocyte count of 11,400/mm3 (neutrophils 79%, lymphocytes 12%, and eosinophils 0.9%), and platelet count of 1.83 lakh/mm3. Biochemical parameters included a total bilirubin of 0.6 mg/dL, Serum glutamic–oxaloacetic transaminase of 105 IU/L, serum glutamic–pyruvic transaminase of 90 IU/L, serum urea of 33 mg/dL, and serum creatinine of 1.06 mg/dL. A presumptive diagnosis of community-acquired pneumonia was established, and the patient was started on empirical broad-spectrum intravenous antibiotics. On day 4 of hospitalization, the patient developed acute respiratory distress characterized by tachycardia (heart rate: 112/min), tachypnea (respiratory rate: 32/min), and hypoxemia (oxygen saturation: 88% on room air). A progressive decline in hemoglobin was noted, from 14.4 g/dL at admission to 12.9 g/dL. On high-resolution computed tomography (HRCT) of the chest, consolidation with air bronchograms and ground-glass opacities (GGOs) was noted in the right upper lobe, accompanied by multifocal patchy areas of consolidation and GGOs in bilateral lung fields [Figure 1a and b]. A moderate pleural effusion on the right side was also identified.Figure 1: High-resolution computed tomography of the chest demonstrating (a) consolidation with air bronchograms (red arrow) and ground-glass opacities (GGOs) in the right upper lobe, (b) multifocal patchy areas of consolidation (blue arrow) and GGOs (red arrows) in bilateral lung fieldsFlexible bronchoscopy was performed, and bronchoalveolar lavage (BAL) samples were obtained from the anterior segment of the right upper lobe. The retrieved fluid was overtly hemorrhagic in appearance. Molecular analysis of the BAL using the BioFire® FilmArray® Pneumonia Panel identified Proteus species at a concentration of 104 copies/mL, along with detection of the Verona integron-encoded metallo-β-lactamase (VIM) resistance gene. Cytological evaluation revealed the presence of hemosiderin-laden macrophages, supporting the diagnosis of DAH. A vasculitis screen, including relevant autoimmune markers, yielded negative results. The patient was treated with a combination of intravenous ceftazidime–avibactam (2 g/0.5 g every 8 h) and intravenous aztreonam (2 g every 8 h). Following initiation of therapy, he exhibited significant clinical improvement, including resolution of fever, respiratory distress, and hypoxemia. His hemoglobin level rose to 13.9 g/dL. At a 2-week follow-up, both clinical assessment and imaging confirmed complete resolution of the pulmonary findings. In the present case, a progressive decline in hemoglobin in conjunction with worsening hypoxemia prompted clinicians to consider etiologies beyond community-acquired pneumonia. HRCT of the chest in DAH classically demonstrates bilateral, centrally predominant GGOs and areas of consolidation.[3,4] Flexible bronchoscopy accompanied by sequential BAL remains the preferred diagnostic approach. In addition, the presence of hemosiderin-laden macrophages, as demonstrated by Prussian blue staining of the BAL fluid, serves as further evidence of alveolar bleeding.[5] Management of DAH remains challenging, particularly due to the paucity of randomized controlled trials outside the context of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. When an underlying etiology is identified, targeted management should be promptly initiated. This includes antimicrobial therapy for infections, withdrawal of offending drugs or toxins, and correction of coagulopathies. Immune-mediated causes such as vasculitis and connective tissue disorders require high-dose systemic corticosteroids and additional immunosuppressive agents.[6] However, it is imperative to rule out infectious causes prior to initiating immunosuppression. Given the urgent nature of DAH, molecular diagnostic tools such as BAL polymerase chain reaction (PCR) panels are preferred over conventional Gram stain and culture due to their rapid turnaround and broader pathogen detection. A variety of infectious organisms have been associated with DAH, primarily through the mechanism of diffuse alveolar injury. Although Proteus species are uncommon pathogens in the respiratory tract, there have been sporadic reports of pneumonia caused by this organism, typically in immunocompromised patients.[7,8]Proteus is a Gram-negative, facultatively anaerobic bacillus classified under the Enterobacteriaceae family. It is noted for its vigorous motility and distinctive swarming behavior on culture media. Generally, its pathogenic potential in pulmonary infections is considered to be low. Our patient, notably immunocompetent with no history of recurrent infections or known risk factors, represents a rare instance of Proteus-associated DAH. Moreover, the strain identified by multiplex PCR from BAL fluid harbored the VIM resistance gene. VIM is one of the most prevalent metallo-β-lactamases found in Gram-negative organisms and confers resistance to carbapenems.[9] For pneumonia caused by carbapenem-resistant Enterobacterales expressing VIM, the recommended therapeutic options include ceftazidime–avibactam plus aztreonam or cefiderocol.[10] In this case, the patient was successfully treated with a 7-day course of intravenous ceftazidime–avibactam combined with aztreonam, without the use of adjunctive corticosteroids. Clinical improvement was evident within 72 h, with resolution of respiratory failure and recovery of hemoglobin levels. This case underscores the critical role of timely recognition, thorough diagnostic assessment, and the use of molecular techniques in identifying infectious etiologies of DAH and facilitating targeted treatment. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.