Granulomatosis with polyangiitis

Classification according to ICD-10
M31.3	Wegener's granulomatosis Necrotizing granulomatosis of the airways
ICD-10 online (WHO version 2019)

The granulomatosis with polyangiitis (GPA) (formerly Wegener's granulomatosis or Wegener's disease , named after the German pathologist Friedrich Wegener ) is a rheumatic systemic disease of the vascular system and is characterized by necrotizing inflammation of the vessels, which with a granuloma formation, in the upper (nasal Sinuses, middle ear, oropharynx ) and the lower airways ( lungs ). In 80 percent of cases there is an inflammation of the kidney corpuscles ( glomerulonephritis , more precisely: Pauci immune glomerulonephritis as a pathohistological correlate) and the formation of microaneurysms in the kidneys. The inflammation of the vessels results in a poor blood supply to the affected organs. In principle, any tissue can be affected.

Other names

Other earlier names for the disease are Wegener 's granulomatosis , Wegener's granulomatosis , Wegener's disease , allergic angiitis and granulomatosis , Wegener-Klinger-Churg-Strauss syndrome , Klinger-Wegener-Churg syndrome (or in a different order Wegener-Klinger-Churg syndrome ), rhinogenic granulomatosis , giant cell granuloarteritis Wegener-Klinger-Churg .

The American College of Rheumatology and American Society of Nephrology recommend speaking of granulomatous polyangiitis (English: granulomatosis with polyangiitis , German: granulomatosis with polyangiitis, GPA). The background to this recommendation is the tendency to move away from honorable terms that are derived from proper names (eponyms) and to prefer descriptive names. This development was initiated by knowledge of Friedrich Wegener's NSDAP membership before and during the Second World War . In the ICD-10, however, the old name is still in use.

Epidemiology

Granulomatosis with polyangiitis is a rare condition that affects about 5-7 people in 100,000. Men get sick more often than women, the peak of the disease is around the age of 50, but children can also get sick.

etiology

The origin of the disease is unknown. Inhalation allergens , an infection of the nasal mucous membranes with Staphylococcus aureus and a genetic disposition probably play a role. Alpha-1 antitrypsin deficiency can sometimes be diagnosed.

Pathogenesis

It is a generalized vasculitis in which neither circulating immune complexes nor a cellular immune reaction of the late type can be detected. It is therefore a pauci-immune vasculitis (Latin pauci = little). It is assumed that it is triggered by autoantibodies . The occurrence of c-ANCA with the target antigen proteinase 3 from neutrophil granulocytes (see below) is pathognomonic .

Symptoms

The symptoms of granulomatosis with polyangiitis are very mixed. In the literature - with the exception of the pleural effusions which also occur in other rheumatic diseases and may be caused by exudate formation - the following frequencies are given:

manifestation		at onset of illness (in%)	in the course of the disease (in%)
kidney	Glomerulonephritis	18th	77
Throat / nose / ears	Total:	73	92
	Sinusitis	51	85
	nasal diseases	36	68
	Otitis media	25th	44
	Hearing loss	14th	42
	Subglottic stenosis	1	16
	Earache	9	14th
	oral lesions	3	10
lung	Total:	45	85
	pulmonary infiltrates	25th	66
	pulmonary nodules	24	58
	Hemoptysis	12	30th
	pleurisy	10	28
eyes	Conjunctivitis	5	18th
	Dacrocystitis	1	18th
	Scleritis	6th	16
	Exophthalmos	2	15th
	Eye pain	3	11
	Loss of vision	0	8th
	Retinal lesions	0	4th
	Corneal lesions	0	1
	Iritis	0	2
Other	Arthralgia / arthritis	32	67
	fever	23	50
	to cough	19th	46
	Skin abnormalities	13	46
	Weight loss (> 10%)	15th	35
	peripheral neuropathy	1	15th
	Involvement of the CNS	1	8th
	Pericarditis	2	6th
	Hyperthyroidism	1	3

diagnosis

• The diagnosis is based on clinical, laboratory and histopathological findings. At the clinical level, the ARA / ACR criteria are used: If 2 of 4 criteria apply, there is a high degree of suspicion of granulomatosis with polyangiitis ( sensitivity 88%, specificity 92%). The ARA / ACR criteria are:
  • Oronasal inflammation
  • Pathological chest x-ray
  • Pathological urine sediment
  • Granulomatous inflammation in the biopsy specimen
• In the vast majority of cases, a biopsy can confirm the suspected diagnosis.
• Histopathologically there is z. B. necrotizing, partially granulomatous vasculitis of small vessels. The granulomas differ from the tuberculosis and sarcoid granulomas . Thurlbeck and Churg describe them as microabscesses and collagen microscopic necroses with an inflammatory wall; Houser, Balis and Mark, Klöppel et al. and Thomas mention “palisade-shaped” granulomas (microabscesses with a histiocyte wall in the manner of a palisade ).
• CRP ( C-reactive protein ), sedimentation rate and creatinine may be increased. It can be used to leukocytosis and hematuria come. In the typical course of glomerulonephritis and granulomatous vasculitis of the respiratory tract, c-ANCA can be detected in about 90 percent of cases, and p-ANCA in about 10 percent . In some patients, a relapse may be preceded by an increase in antibody titre. The antibody titer, however, is not, as previously assumed, a reliable indicator of disease activity.
• X-ray images often show shadows in the paranasal sinuses and infiltrations in the lungs, while computed tomography (CT) scans of the chest show granulomas , caverns and scars within the lung tissue. In the ENT area, the chronic inflammation can lead to bone destruction and ulceration.

Differential diagnosis

Differentiation from Goodpasture's syndrome , bronchial carcinoma with necrotic cavity (typically squamous epithelium ) is necessary. Furthermore, the clinically similar eosinophilic granulomatosis with polyangiitis , which was previously also known as Churg-Strauss syndrome .

therapy

In the locally limited initial stage, treatment is given with a combination of methotrexate and prednisolone .

If a life-threatening or organ-threatening generalization has occurred, attempts are made to achieve remission with immunosuppressants ( induction therapy ): prednisolone plus cyclophosphamide or prednisolone plus rituximab (approved since 2013) or, if the disease progresses, methotrexate plus prednisolone. Options for the reserve are mycophenolate mofetil , 15-deoxyspergualin , infliximab and immunoglobulins . In the case of life-threatening pulmonary bleeding or kidney failure requiring dialysis , plasmapheresis is used. Other therapeutic agents used are etanercept , ciclosporin , leflunomide and anti-thymocyte globulin (ATG).

After reaching remission, maintenance therapy includes azathioprine and, in decreasing doses, prednisolone. Co-trimoxazole is used to treat or prevent colonization of the nasal cavity with Staphylococcus aureus .

In 35–70 percent of the sick, the disease relapses approximately 2 years after treatment has been discontinued (in the absence of any disease activity), typically in the same organ or organ system as at the beginning. This relapse can be treated with the same prospect of remission as the first occurrence. However, the disease cannot be cured, it is a chronic disease.

forecast

Without treatment, the disease leads to death within about 6 months via rapid progressive glomerulonephritis (RPGN) (immune complex-negative or pauci-immune glomerulonephritis).

With combined cyclophosphamide-glucocorticoid therapy, a marked improvement is achieved in 90% of the patients, 75% achieve a complete remission . About 50% of remissions are later associated with one or more relapses. The quality of life is often severely restricted. According to a 2011 study, 75% of all vasculitis patients suffer significantly from fatigue , even after the onset of remission . You are burdened with pain and external steroid-related changes such as hair loss, weight gain, acne and canker sores.

literature

• F. Wegener: About generalized, septic vascular diseases. In: Verh Dtsch Pathol Ges. 29, 1937, p. 202.
• F. Wegener: About a peculiar rhinogenic granulomatosis with particular involvement of the arterial system and the kidneys. In: Contribution Pathol Anat Allg Pathol. 102, 1939, p. 36.
• R. Socias, A. Pozniak: Translation of a classic paper: Friedrich Wegener: On generalized septic vessel disease. In: Thorax. , 1987, 42, p. 918.
• L. Strauss, KV Lieberman, J. Churg: Pulmonary Vasculitis. In: AP Fishman (Ed.): Pulmonary Diseases and Disorders. 2nd Edition. McGraw-Hill, New York 1988, p. 1128.
• RY Leavitt, AS Fauci, DA u. a .: The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. In: Arthritis Rheum. , 1990, 33, pp. 1101-1107.

Individual evidence

1. ↑ named after Friedrich Wegener (1907–1990), Heinz Klinge (1907–1983), Jacob Churg (1910–2005) and Lotte Strauss (1913–1985), see A. Grzybowski, JM Rohrbach, Should we refer to the eponym “Wegener 'cal granulomatosis'? A historical digression , in: Klinische Monatsblätter für Augenheilkunde , vol. 228.2011, pp. 641–643 ( abstract ), and Fernando PF de Campos, Stephen A. Geller, Churg-Strauss Syndrome: a syndrome described on clinical observation and autopsy findings , in: Autopsy and Case Reports , vol. 3.2013, pp. 1-4
2. ^ Definition and opinion of the American College of Rheumatology accessed on March 10, 2018
3. ↑ RJ Falk et al. a. In: J Am Soc Nephrol . 2011, 22, pp. 587-588.
4. ↑ A. Woywodt, M. Haubitz, H. Haller, EL Matteson: Wegener's granulomatosis. In: The Lancet . 2006, 367, pp. 1362-1366.
5. ↑ DIMDI - ICD-10-GM Version 2014. (No longer available online.) Archived from the original on January 16, 2014 ; accessed on January 16, 2014 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.  
6. ↑ Lucey et al. a .: Alpha1-Antitrypsin Deficiency. In: New England Journal of Medicine . 2009, vol 360 (26), pp. 2749-2757 (English).
7. ↑ Berthold Jany, Tobias Welte: Pleural effusion in adults - causes, diagnosis and therapy. In: Deutsches Ärzteblatt. Volume 116, No. 21, (May) 2019, pp. 377-385, here: pp. 379 f.
8. ↑ GS Hoffman et al. a .: Wegener's granulomatosis: An analysis of 158 patients . In: Ann Intern Med . 1992, 116, p. 488, quoted from: Harrison's internal medicine. German edition of the 15th edition. Berlin 2003, ISBN 3-936072-10-8 , pp. 2146-2149.
9. ↑ William M. Thurlbeck, Andrew M. Churg: Pathology of the Lung . Thieme, 1995, ISBN 0-86577-534-6 , p. 401 ff . ( books.google.com ).
10. ↑ Stuart Houser, Ulysses J. Balis, Eugene J. Mark: Lung Pathology: A Consultative Atlas . Springer, 2005, ISBN 1-59259-937-0 , pp. 266 ( books.google.com ).
11. ^ Günter Klöppel, Pierre Rudolph, Th Mentzel, Antonio Cardesa, Hans-Heinrich Kreipe, Pieter J Slootweg, Wolfgang Remmele: Pathology . Springer, 2009, ISBN 978-3-540-72884-9 , pp. 54 ( books.google.com ).
12. ↑ Carlos Thomas: Pathology - Histopathology: textbook and atlas for making findings and differential diagnosis . Schattauer Verlag, 2006, ISBN 3-7945-2429-2 , p. 92 ( books.google.com ).
13. ↑ MM Boomsma, CA Stegeman, MJ van der Leij u. a .: Prediction of relapses in Wegener's granulomatosis by measurement of antineutrophil cytoplasmic antibody levels: a prospective study. In: Arthritis Rheum . September 2000; 43 (9), pp. 2025-2033.
14. ↑ emedicine.medscape.com
15. ↑ ^{a b c} Gerd Herold : Internal medicine . Cologne 2005.
16. ↑ DRW Jayne et al. a. on behalf of the European Vasculitis Study Group: Randomized Trial of Plasma Exchange or High-Dosage Methylprednisolone as Adjunctive Therapy for Severe Renal Vasculitis. In: J Am Soc Nephrol. , 2007, 18, pp. 2180-2188.
17. ^ RAF de Lind van Wijngaarden u. a. for the European Vasculitis Study Group (EUVAS): Chances of Renal Recovery for Dialysis-Dependent ANCA-Associated Glomerulonephritis. In: J Am Soc Nephrol. , 2007, 18, pp. 2189-2197.
18. ↑ Delesha Carpenter, Robert F. DeVellis: Quality of Life Issues in vasculitis. In: Luis M. Amezcua-Guerra (Ed.): Advances in the Etiology, Pathogenesis and Pathology of Vasculitis. InTech, 2011, ISBN 978-953-307-651-5 .

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !