January 2024 Medical Image of the Month: Polyangiitis Overlap Syndrome (POS) Mimicking Fungal Pneumonia

Figure 1. PA chest radiographs obtained on 9/14/23 (A) and approximately 2.5 months later (B) demonstrates rapidly growing cavitary masses in the upper lungs (arrows). The rapid interval growth is more suggestive of an inflammatory as opposed to malignant process. To view Figure 1 in a separate, enlarged window click here.

Figure 2. Axial reconstructions from an unenhanced chest CT (A,B) demonstrate multiple areas of mass-like consolidation with some areas of cavitation and some internal air bronchograms. As was surmised from the CXRs, the appearance suggests an infections/inflammatory etiology. To view Figure 2 in a separate, enlarged window click here.

Figure 3. H&E (A) and GMS (B) stains of a specimen from biopsy of right upper lobe lesion. There is an organizing inflammatory process with extensive necrosis and no evidence of infectious organism. H&E staining of a renal biopsy (C) demonstrates chronic and active necrotizing and crescentic glomerulosclerosis with diffuse interstitial fibrosis and tubular atrophy. Taken in conjunction with the history and lack of any other findings to suggest infection, histopathological findings were deemed to be consistent with active granulomatosis with polyangiitis.  To view Figure 3 in a separate, enlarged window click here.

A 32-year-old woman with a history including hypertension, end-stage renal disease requiring dialysis, asthma, nonischemic cardiomyopathy, and migraines, was directly transferred to our hospital in November 2023 for the evaluation of hemoptysis. The patient reported a two-week history of a nonproductive cough, runny nose, muscle aches, subjective fevers, chills, fatigue, nausea, and decreased appetite. Within the past 2 days the patient had also developed hemoptysis, with 5-6 episodes per day.

Initial investigations, including chest X-ray and CT chest, revealed large biapical pulmonary consolidations with cavitation. Multiple nodular densities were observed throughout both lungs (Figures 1 and 2). The patient denied any recent sick contacts, travel history, and prior tuberculosis infection. She did, however, disclose a period of incarceration from 2011 to 2019.

Upon arrival at our hospital, the patient recounted a relatively normal state of health until January 2023 when she underwent a two-month hospitalization, culminating in the diagnosis of end-stage renal disease by biopsy at an outside facility. She attributed this to anautoimmune disease, for which she did not receive immunosuppressive therapy at the time. Subsequent hospitalization in September 2023 for rhinovirus pneumonia led to the diagnosis of heart failure with a reduced ejection fraction of 15-20%, determined to be of nonischemic origin.

In our ED vital signs revealed a heart rate of 110, blood pressure of 180/90 mmHg, normal respiratory rate, and no hypoxia on room air. Laboratory results were significant for leukocytosis 18.7x10⁹/L with high eosinophils count of 2.32x10⁹/L, elevated potassium 5.7 mmol/L, BUN 51 mg/dL, and creatinine 9.5 mg/dL. Chest X-ray depicted bilateral upper lung consolidations, notably worsened on the right with central cavitation (Figure 1B). Additional nodularity was observed in the left mid-lung, which was new in comparison to a prior chest x-ray done in September 2023 (Figure 1A).

Following her admission, an extensive infectious workup, including TB QuantiFERON testing, lumbar puncture, bronchoscopy with BAL, and blood cultures, was conducted. The results were unremarkable. Transbronchial biopsies from the right upper lobe cavity revealed an organizing inflammatory process with extensive necrosis, negative for neoplasm and infectious staining including GMS & acid-fast bacilli (Figure 3A,3B). An autoimmune panel revealed elevated ESR, CRP, PR3 antibody, and positive c-ANCA, leading to a diagnosis of Polyangiitis overlap syndrome. Treatment commenced with IV methylprednisone, transitioning to oral prednisone (60 mg daily) with a gradual taper over the next eight weeks. Inpatient administration of rituximab was initiated, with plans for three more infusions as part of her induction therapy.

According to the data from the French Vasculitis Study Group Registry (1), among the 795 patients with granulomatosis with polyangiitis (GPA), 354 individuals (44.5%) exhibited elevated blood eosinophil counts. Notably, hypereosinophilia, primarily of mild-to-moderate severity (ranging from 500 to 1500/mm³), was identified in approximately one-quarter of GPA patients at the time of diagnosis. In contrast, severe eosinophilia (>1500/mm3) was observed in only 28 patients (8%). Furthermore, this subset with severe eosinophilia was noted to have worse renal function at the time of presentation. Whereas in a retrospective European multicentre cohort published by Papo et al. (2), ANCA status was accessible for 734 EGPA patients with only 16 patients (2.2%) having PR3-ANCA. Notably, at baseline, PR3-ANCA positive patients, in comparison to those with MPO-ANCA and ANCA-negative individuals, exhibited a lower prevalence of active asthma and peripheral neuropathy. Conversely, they manifested a higher incidence of cutaneous manifestations and pulmonary nodules. Adding to the complexity, EGPA, characterized by peripheral blood eosinophilia, asthma, and chronic rhinosinusitis, contrasts with GPA, which manifests pulmonary nodules without eosinophilic infiltration and usually a more severe renal disease.

Polyangiitis overlap syndrome (POS), previously published by Leavitt and Fauci (3), was defined as systemic vasculitis that does not fit precisely into a single category of classical vasculitis or overlaps more than one subtype of vasculitis. Several polyangiitis overlap syndromes have been identified since 1986; however, less than 20 case reports of an overlap syndrome involving both GPA and EGPA have been published so far. As per the literature review performed by Bruno et al. (4), most of the reported POS cases had lung involvement with over half developed alveolar hemorrhage. They noted genetic and clinical heterogeneity in the pathogenesis of polyangiitis overlap syndrome suggesting distinct clinical phenotypes and outcomes to therapy. Notably, treatment strategies in polyangiitis overlap syndrome are usually tailored to the severity of the disease rather than the ANCA phenotype, leading to favorable outcomes in most cases.

John Fanous MD¹, Clint Jokerst MD², Rodrigo Cartin-Ceba MD¹

Division of Pulmonology¹and Department of Radiology²

Mayo Clinic Arizona, Scottsdale, AZ USA

References

1. Iudici M, Puéchal X, Pagnoux C, et al.; French Vasculitis Study Group. Significance of eosinophilia in granulomatosis with polyangiitis: data from the French Vasculitis Study Group Registry. Rheumatology (Oxford). 2022 Mar 2;61(3):1211-1216. [CrossRef] [PubMed]
2. Papo M, Sinico RA, Teixeira V, et al.; French Vasculitis Study Group and the EGPA European Study Group. Significance of PR3-ANCA positivity in eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Rheumatology (Oxford). 2021 Sep 1;60(9):4355-4360. [CrossRef] [PubMed]
3. Leavitt RY, Fauci AS. Pulmonary vasculitis. Am Rev Respir Dis. 1986 Jul;134(1):149-66. [CrossRef] [PubMed]
4. Bruno L, Mandarano M, Bellezza G, Sidoni A, Gerli R, Bartoloni E, Perricone C. Polyangiitis overlap syndrome: a rare clinical entity. Rheumatol Int. 2023 Mar;43(3):537-543. [CrossRef] [PubMed]

Cite as: Fanous J, Jokerst C, Cartin-Ceba R. January 2024 Medical Image of the Month: Polyangiitis Overlap Syndrome (POS) Mimicking Fungal Pneumonia. Southwest J Pulm Crit Care Sleep. 2024;28(1):5-8. doi: https://doi.org/10.13175/swjpccs052-23 PDF

December 2023 Medical Image of the Month: Metastatic Pulmonary Calcifications in End-Stage Renal Disease

Figure 1. Pulmonary function testing results for the patient demonstrate severe restriction with a reduced diffusion capacity with a corrected DLCO 50% of predicted and FVC 45% of predicted. To view Figure 1 in an enlarged, separate window click here.

Figure 2. Unenhanced chest CT images in the axial plane reconstructed with lung (A) and soft tissue (B) display settings. There are innumerable small solid pulmonary nodules with a peripheral distribution, some subpleural sparing, and architectural distortion (A). On soft tissues windows (B) the fact that the nodules are calcified are well-appreciated in the anterior and lateral right mid-lung. To view Figure 2 in a separate, enlarged window click here.

A 51-year-old African-American man with medical history of obesity (BMI 36) and hypertension was seen in pulmonary consultation for preoperative evaluation of kidney transplantation. End-Stage renal disease (ESRD) was diagnosed 7 years before evaluation secondary to resistant hypertension. The patient has been on hemodialysis since then. The patient was on carvedilol, hydralazine, losartan, and calcitriol. He had prescribed sevelamer and prednisone, but he was not taking them. His main symptoms were 3-year chronic dyspnea on exertion and mild morning cough productive of small amounts of clear sputum. He has had no chest pain, wheezes, hemoptysis, fevers, or dizziness. He had trace lower extremity edema. He worked as a forklift operator. He has had no relevant exposures and was a lifetime nonsmoker.

The patient was diagnosed with cryptogenic organizing pneumonia 5 years ago and was on prednisone taper with subjective improvement of symptoms. He has not had lung function testing or biopsies done at that time. He was maintained on 3L oxygen with activity to targets oxygen saturation of 90%. On examination VS: BP 216/100, HR 94, temperature 36.7 °C, SpO2 88 % RA. He was not in respiratory distress. Chest auscultation: symmetrical breath sounds, no added sounds. Examination of the heart, abdomen and rest of the systems were normal. He had trace bilateral pedal edema and clubbing in all digits.

Figure 1 shows his most recent pulmonary function test illustrating a severe restrictive defect with reduced diffusion capacity. Echocardiogram showed ejection fraction of 54%, mild left ventricular hypertrophy and mild diastolic dysfunction. Representative slices of his most recent computed tomography (CT) of the chest are shown in figure 2 and demonstrate multiple scattered small, solid, and calcified pulmonary nodules.

Pulmonary calcifications can either be secondary to hypercalcemia from benign or malignant causes {1}. Such calcification would occur in normal lung tissue due to elevated calcium-phosphate product and is termed metastatic {2,3}. It is thought to occur with higher concentrations of free hydrogen ions, especially in less ventilated areas (West zone 3) with lower pH (more acidotic), leading to calcium-magnesium phosphate compounds (whitlockite-like). Dystrophic calcification on the other hand develops secondary to injury from granulomatous diseases, infections or inherited pulmonary alveolar microlithiasis {4}.

Most cases of metastatic pulmonary calcification are due to ESRD-related hypercalcemia {2}. Most patients are asymptomatic and diagnosed incidentally. Some patients may have non-productive cough, progressive dyspnea, and hypoxia. Lung function testing could show normal or restrictive ventilatory defects, often with impaired diffusion of carbon monoxide. CT scans are diagnostic (Figure 2) and show distinctive diffuse calcifications (sometimes solid and sometimes manifesting as centrilobular ground glass). Bone scintigraphy using technetium-99 diphosphonate scanning would show these calcifications along other parts of the body affected with reported higher sensitivity compared to standard x-ray {5}.

Management is geared towards controlling levels of calcium through phosphate binders, dialysis dosing, and/or parathyroidectomy. Our patient was ultimately evaluated for combined lung/kidney transplantation due to his severe restrictive pulmonary defects.

Abdelmohaymin Abdalla MD¹, Clinton Jokerst MD², Umesh Goswami MD¹

Division of Pulmonary and Critical Care Medicine¹

Mayo Clinic Arizona, Phoenix, AZ USA

Department of Radiology²

Mayo Clinic Arizona, Phoenix, AZ USA

References

1. Kaltreider HB, Baum GL, Bogaty G, McCoy MD, Tucker M. So-called "metastatic" calcification of the lung. Am J Med. 1969 Feb;46(2):188-96. [CrossRef] [PubMed]
2. Conger JD, Hammond WS, Alfrey AC, Contiguglia SR, Stanford RE, Huffer WE. Pulmonary calcification in chronic dialysis patients. Clinical and pathologic studies. Ann Intern Med. 1975 Sep;83(3):330-6. [CrossRef] [PubMed]
3. Kuzela DC, Huffer WE, Conger JD, Winter SD, Hammond WS. Soft tissue calcification in chronic dialysis patients. Am J Pathol. 1977 Feb;86(2):403-24. [PubMed]
4. Chan ED, Morales DV, Welsh CH, McDermott MT, Schwarz MI. Calcium deposition with or without bone formation in the lung. Am J Respir Crit Care Med. 2002 Jun 15;165(12):1654-69. [CrossRef] [PubMed]
5. Faubert PF, Shapiro WB, Porush JG, Chou SY, Gross JM, Bondi E, Gomez-Leon G. Pulmonary calcification in hemodialyzed patients detected by technetium-99m diphosphonate scanning. Kidney Int. 1980 Jul;18(1):95-102. [CrossRef] [PubMed]

Cite as: Abdalla A, Jokerst C, Goswami U. December 2023 Medical Image of the Month: Metastatic Pulmonary Calcifications in End-Stage Renal Disease. Southwest J Pulm Crit Care Sleep. 2023;27(6):67-69. doi: https://doi.org/10.13175/swjpccs049-23 PDF