GRANULOMATOSIS WITH POLYAANGIITIS: An Ortho/neuro doc

GRANULOMATOSIS

1. GRANULOMATOSIS WITH POLYAANGIITIS (GP) BY OKEKE, FRANKLYN CHINONSO 239098001 A PRESENTATION SUBMITTED TO THE DEPARTMENT OF PHYSIOTHERAPY, SCHOOL OF POSTGRADUATE STUDIES, UNIVERSITY OF LAGOS, IN PARTIAL FULFILMENT OF THE REQUIREMENT FOR THE AWARD OF MASTER OF SCIENCE IN PHYSIOTHERAPY APRIL, 2024.

2. Outline Introduction Epidemiology Etiology Pathophysiology Clinical presentation Complications Diagnosis Differential diagnosis Management References

3. Introduction Granulomatosis with polyangiitis (GPA), formerly termed  Wegener's granulomatosis . It is a rare autoimmune disease characterized by necrotizing inflammation of small vessels wall ( Miłkowska-Dymanowska et al, 2019 ). It involves the upper respiratory tract, lower respiratory tract (bronchi and lung), and kidney, with varying degrees of disseminated vasculitis .

4. Epidemiology The reported incidence of GPA varies from 2 to 12 per million people and the prevalence is from 24 to 157 per million people ( Ghorbel et al, 2017). GPA affects both sexes. While mean age of occurrence is 45 years (Xavier, 2020). Ethnicity may be relevant because GPA is rarely seen in Africa ( Ghorbel et al, 2017).

5. Etiology The etiology of GPA is still unknown (Banerjee et al, 2021). Scientific investigations of GPA is warranted because its severity, clinical heterogeneity, fast disease manifestation and end-organ damage .

6. Pathogenesis Neutrophils produce the proteinase 3 (PR3) autoantigen and their regulation is altered in patients with GPA ( Xavier,2020 ). Patients with GPA have autoantibodies directed against PR3 in neutrophils. When recruited to the inflammation site, these cells have a crucial role in defending against microbes but can also contribute to tissue damage (Xavier,2020).  

7. Pathophysiology The formation of the granulomas in GPA begins with the formation of neutrophilic microabscesses . The granulomas in GPA ultimately result in partial or total occlusion of blood vessels . The granulomas in GPA are not well-formed, unlike the ones in sarcoidosis or tuberculosis, and consist of giant cells surrounded by plasma cells, lymphocytes, and dendritic cells. These cells can damage the submucosa and penetrate the surrounding tissues, cartilage, or bone, resulting in necrosis and permanent deformities .

8. Clinical presentation Respiratory; Symptoms include  sinus pain, discolored or bloody fluid from nose, and nasal ulcers. And occurs in the upper respiratory tract in nearly all patients.   Common signs include;   rhinorrhea (runny nose). Lungs; Possible signs and symptoms can include cough, hemoptysis , shortness of breath, and chest discomfort. System and symptoms n  (%) Constitutional symptoms* 48 (80%) Renal involvement 42 (70%)  Hypertension 42 (100%)   Microscopic hematuria 37 (89%)  Hypertension 42 (100%)  Rapidly progressive renal failure 28 (66%)   Nephrotic syndrome 8 (19%)  Macroscopic hematuria 5 (11%)  Asymptomatic urinary sediments 7 (16%) Respiratory involvement 38 (63%)  Cough 14 (36%)   Dyspnea 8 (21%)   Hemoptysis 6 (16%)  Nasal discharge 5 (13%)  Chronic sinusitis 4 (11%)  Ear discharge 2 (5%)  Palate and nasal perforation 2 (5%)  Diffuse alveolar haemorrhage 2 (5%) Chest X-ray and CT 28 (47%)  Cavities 8 (29%)  Nodules 6 (21%) Mucocutaneous lesions** 29 (48%) Articular manifestation 16 (26%) Neurological involvement 15 (25%)  Peripheral neuropathy 7 (46%)   Mononeuritis multiplex 4 (27%)  Foot drop 3 (20%)  Stroke 1 (7%) Ocular 7 (11%)   Iritis 3 (42%)  Uveitis 3 (42%)  Cornea melting 1 (16%) Cardiac***

9. Clinical presentations cont‘d Musculoskeletal symptoms include; pain in the muscle and joints, along with joint swelling. Other signs and symptoms can include developing skin lesions. The eyes can be affected causing conjunctivitis, scleritis , episcleritis causing double vision, redness, burning, and pain.  Symptoms involving the eyes require immediate medical attention.

10. Complications Common complications due to the disease itself:  Hearing loss  Permanent loss of vision  Saddle nose deformity or septal perforation  Acute hypoxic respiratory failure due to diffuse pulmonary hemorrhage Chronic kidney disease or end-stage renal disease  Mononeuritis multiplex 

11. Complications cont‘d Complications due to immunosuppressive treatment: (refer to toxicity and side effect management) Infections  Cancers including lymphomas and myelodysplastic syndromes Infusion reactions and death

12. Diagnosis Various diagnostic criteria have been proposed to diagnose GPA and distinguish the disease from other vasculitides .  The ACR criteria include: a) Urinary sediment showing red blood cell casts or more than five red blood cells per high power field, b) Abnormal findings on chest radiograph, c) Oral ulcer or nasal discharge, and d) Granulomatous inflammation on biopsy ( Cloe and Patrice 2015 . ). The presence of two or more out of the above-mentioned four criteria was associated with a 92% specificity and 88% sensitivity.

13. Diagnosis cont‘d The ELK (E stands for ears, nose, and throat or upper respiratory tract, L for lung, and K for kidney) proposed by DeRemee utilizes ANCA to diagnose. Per these criteria, any typical manifestation involving typical histopathological finding qualifies for a diagnosis of GPA .

14. Differential diagnosis The differential diagnosis is broad, and many conditions could mimic GPA. Microscopic polyangiitis   Churg - Strauss syndrome   Renal limited vasculitis   Mixed cryoglobulinemia Systemic lupus erythematosus Sarcoidosis   Rheumatoid arthritis

15. Differential diagnosis cont‘d Amyloidosis Infective endocarditis  Sepsis  Mycobacterial infections  Lymphomatoid granulomatosis   Lymphomas  And drug toxicities

16. Management Management should be adjusted to individual patient. Glucocorticoids and cyclophosphamide are the most commonly used medication by the doctors (Eugene et al, 2018).

17. Physiotherapy management Exercise Programs; Use of exercise programs to improve muscle strength, flexibility, and cardiovascular fitness. Respiratory Management; GPA can affect the lungs, leading to respiratory complications. Physiotherapists can teach breathing techniques, airway clearance methods, and exercises to improve lung function. Joint Mobility; Physiotherapy can help maintain joint mobility and prevent stiffness or deformity.

18. Physiotherapy management Pain Management; Physiotherapists may use techniques such as manual therapy techniques, therapeutic ultrasound to alleviate pain and improve comfort . Assistive Devices and Orthotic; Physiotherapists can recommend and fit assistive devices like canes or orthotics to improve mobility and reduce strain on affected joints . Education and Self-management; They provide education on the disease process, energy conservation techniques, and strategies for managing symptoms during daily activities.

19. Conclusion In the treatment of Granulomatosis with Polyangiitis , physiotherapy should play a crucial role in managing symptoms, improving function, and enhancing overall quality of life through tailored exercise programs, respiratory management techniques, pain relief strategies, and education on self-management . However, there is currently no enough evidence suggesting physiotherapy interventions in the management.

20. References Joseph P. L III, Ariis D, Henry T, John A (2018). Granulomatosis with Polyangiitis (Wegener's Granulomatosis ): Evolving Concepts in Treatment. Semin Respir Crit Care Med. 39(04): 434-458. DOI: 10.1055/s-0038-1660874 Banerjee P, Jain A., Kumar U (2021). Epidemiology and genetics of granulomatosis with polyangiitis .  Rheumatol Int  41:2069–2089. https://doi.org/10.1007/s00296-021-05011-1

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