PULMONARY-RENAL SYNDROME: DIFFICULTIES OF DIFFERENTIAL DIAGNOSIS

The study objective is to demonstrate the difficulty of differential diagnosis in pulmonary-renal syndrome using a clinical case as an example.

Materials and methods. Male patient A., 68 years old, retired, was hospitalized at the N.I. Pirogov City Clinical Hospital № 1 in December of 2017 with complaints of inefficient cough, fever of 39 °С, weakness, apnea, weight loss up 10 kg in 3 months. Examination revealed skin and mucosa paleness, calf edema, heart beat of 102 bpm, normal rhythm, arterial pressure 130/80 mm Hg, respiratory rate 22 breaths per min. Auscultation revealed harsh respiration in the lungs, weakened in the lower parts, fine moist rales. Anemia (hemoglobin – 53 g/l, erythrocytes – 1.85 × 1012/l, serum iron – 3.1 µmol/l), elevated urea up to 41.4 mmol/l, creatinine up to 843.1 µmol/l (glomerular filtration rate – 6 ml/min/1.73 m2), leukocytes up to 12.5 × 109/l, С-reactive protein up to 124.96 mg/l were diagnosed. Clinical urine analysis showed proteinuria 0.47 g/l. Computed tomography of the chest revealed pronounced infiltrative changes in tissues of both lungs, more on the right, alveolitis, bronchiolitis in the middle lobe on the right, 5th segment on the left. Lymphadenopathy mediastinal was diagnosed. After examination (multiple bacteriological blood, sputum tests, interferon-gamma release assay, echocardiography, bronchoalveolar lavage, sterna puncture, esophagogastroduodenoscopy, colonoscopy, etc.), oncological pathology, tuberculosis of the lungs, sepsis, infections endocarditis and other infectious pathologies were excluded. Antibacterial courses prescribed earlier were ineffective. Immunological blood test revealed high titers (1:1280) of antineutrophil cytoplasmic antibodies (ANCA) with perinuclear fluorescence type (myeloperoxidase specificity), negative antibodies to glomerular basal membrane which allowed to diagnose ANCA-associated vasculitis.

Results. Considering the data of clinical, lab, and instrumental examination, the patient was diagnosed with microscopic polyangiitis, ANCA-associated, affecting the lungs (disseminated interstitial lung disease with bronchiolitis) and kidneys (rapidly progressive glomerulonephritis), intrathoracic lymphadenopathy, activity grade III (BVAS index – 23 points). Grade II respiratory failure. Chronic kidney disease 5D (glomerular filtration rate – 6 ml/min/1.73 m2). Grade II arterial hypertension, risk 4. Grade II pulmonary hypertension. Chronic heart failure 2А, functional class IV. Mixed anemia (iron-deficient, chronic disease), severe. Disseminated polyposis of the colon (hyperplastic type). At the hospital, antibacterial drugs (cefoperazone sulbactam), antifungal (fluticasone) were administered, anemia was corrected (iron-containing drugs and erythropoietin, hemotransfusion), hemodialysis. Cyclophosphane 400 mg was administered intravenously, a week later – 800 mg. Methylprednisolone (60 mg/day), co-trimoxazole (480 mg 3 times a week) were prescribed. A pronounced improvement was observed due to the therapy: body temperature normalization, decreased apnea, cough, weakness, increased appetite. The patient was discharged with recommendation for continuation of cytostatic therapy per the regimen and prescription for programmed hemodialysis at the place of residence.

Conclusion. This clinical case demonstrates a necessity of considering ANCA-associated vasculitis during differential diagnosis of pulmonary-renal syndrome. Timely diagnosis and active cytostatic therapy play a principal role in treatment and promote deceleration of disease progression and improve prognosis.

1. Jennette J.C., Falk R.J., Hu P, Xiao H. et al. Pathogenesis of antineutrophil cytoplasmic autoantibody – associated small-vessel vasculitis. Annu Rev Pathol 2013;8(1):139–60.

2. Federal clinical guidelines for the diagnosis and treatment of systemic vasculitis, 2013. URL access mode: https://diseases.medelement.com/disease/системныеваскули-рекомендациирф/15090. (In Russ.)

3. Jennette J.C., Falk R.J., Bacon P.A. et al. 2012 revised International Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013;65(1):1–11.

4. Shostak N.A., Klimenko A.A. Systemic vasculitis: new in classification, diagnosis and treatment. Klinitsist = The Clinician 2015;9(2):8–12. (In Russ.)

5. Ntatsaki E., Watts R.A., Scott D.G. Epidemiology of ANCA-associated vasculitis. Rheum Dis Clin North Am 2010;36(3):447–61.

6. Jennette J.C., Falk R.J., Hu P, Xiao H. et al. Pathogenesis of antineutrophil cytoplasmic autoantibody – associated small-vessel vasculitis. Annu Rev Pathol 2013;8(1):139–60.

7. Watts R.A., Mooney J., Skinner J. et al. The contrasting epidemiology of granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis. Rheumatology (Oxford) 2012;51(5):926–31.

8. Jennette J.C., Falk R.J., Bacon P.A. et al. 2012 revised International Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013;65(1):1–11.

9. Fujimoto S., Watts R.A., Kobayashi S. et al. Comparison of the epidemiology of anti-neutrophil cytoplasmic antibody vasculitis between Japan and the U.K. Rheumatology (Oxford) 2011;50(10):1916–20.

10. Ntatsaki E., Watts R.A., Scott D.G. Epidemiology of ANCA-associated vasculitis. Rheum Dis Clin North Am 2010;36(3):447–61.

11. Kozlovskaya N.L., Gordovskaya N.B., Korotchaeva Yu.V. PROJECT of National guidelines for the diagnosis and treatment of ANCA-associated glomerulonephritis (kidney damage in ANCA-associated vasculitis), 2014. URL access mode: http://nonr.ru/wp-content/uploads/2013/11/Рекомендации-поАНЦА-ГН-оконч.pdf. (In Russ.)

12. Watts R.A., Mooney J., Skinner J. et al. The contrasting epidemiology of granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis. Rheumatology (Oxford) 2012;51(5):926–31.

13. Khan I., Watts R.A. Classification of ANCA-associated vasculitis. Curr Rheumatol Rep 2013;15(12):383. DOI: 10.1007/s11926-013-0383-6.

14. Fujimoto S., Watts R.A., Kobayashi S. et al. Comparison of the epidemiology of anti-neutrophil cytoplasmic antibody vasculitis between Japan and the U.K. Rheumatology (Oxford) 2011;50(10):1916–20.

15. Moiseev S.V., Novikov P.I., Meshkov A.D., Ivanitskiy L.V. ANCA-associated vasculitis: controversial issues of classification, diagnosis and evaluation of activity and current approaches to treatment. Klinicheskaya farmakologiya i terapiya = Clinical Pharmacology and Therapy 2014;23(1):44–50. (In Russ.)

16. Kozlovskaya N.L., Gordovskaya N.B., Korotchaeva Yu.V. PROJECT of National guidelines for the diagnosis and treatment of ANCA-associated glomerulonephritis (kidney damage in ANCA-associated vasculitis), 2014. URL access mode: http://nonr.ru/wp-content/uploads/2013/11/Рекомендации-поАНЦА-ГН-оконч.pdf. (In Russ.)

17. Semenkova E.N. Systemic necrotizing vasculitis. Moscow: Russian Doctor, 2001. 96 p. (In Russ.)

18. Khan I., Watts R.A. Classification of ANCA-associated vasculitis. Curr Rheumatol Rep 2013;15(12):383. DOI: 10.1007/s11926-013-0383-6.

19. Nasonov E.L., Baranov A.A., Shilkina N.P. Vasculitis and vasculopathy. Yaroslavl: Upper Volga, 1999. 616 p. (In Russ.)

20. Moiseev S.V., Novikov P.I., Meshkov A.D., Ivanitskiy L.V. ANCA-associated vasculitis: controversial issues of classification, diagnosis and evaluation of activity and current approaches to treatment. Klinicheskaya farmakologiya i terapiya = Clinical Pharmacology and Therapy 2014;23(1):44–50. (In Russ.)

21. Flossmann O., Berden A., de Groot K. et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 2011;70(3):488–94.

22. Semenkova E.N. Systemic necrotizing vasculitis. Moscow: Russian Doctor, 2001. 96 p. (In Russ.)

23. Jones R.B., Tervaert J.W., Hauser T. et al. European Vasculitis Study Group: Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010;363(3):211–20.

24. Nasonov E.L., Baranov A.A., Shilkina N.P. Vasculitis and vasculopathy. Yaroslavl: Upper Volga, 1999. 616 p. (In Russ.)

25. Stone J.H., Merkel P.A., Spiera R. et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010;363(3):221–32.

26. Flossmann O., Berden A., de Groot K. et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 2011;70(3):488–94.

27. Charles P., Bienvenu B., Bonnotte B. et al. Rituximab: recommendations of the French Vasculitis Study Group (FVSG) for induction and maintenance treatments of adult, antineutrophil cytoplasm antibody-associated necrotizing vasculitides. Presse Med 2013;42(10):1317–30.

28. Jones R.B., Tervaert J.W., Hauser T. et al. European Vasculitis Study Group: Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010;363(3):211–20.

29. Guillevin L., Pagnoux C., Seror R. et al. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine 2011;90(1):19–27

30. Stone J.H., Merkel P.A., Spiera R. et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010;363(3):221–32.

31. Charles P., Bienvenu B., Bonnotte B. et al. Rituximab: recommendations of the French Vasculitis Study Group (FVSG) for induction and maintenance treatments of adult, antineutrophil cytoplasm antibody-associated necrotizing vasculitides. Presse Med 2013;42(10):1317–30.

32. Guillevin L., Pagnoux C., Seror R. et al. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine 2011;90(1):19–27