Granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA) is a rare, long-term, systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis). It is an autoimmune disease and a form of vasculitis that affects small- and medium-sized vessels in many organs, but most commonly affects the upper respiratory tract, lungs, and kidneys. The signs and symptoms of GPA are highly varied and reflect which organs are supplied by the affected blood vessels. Typical signs and symptoms include nosebleeds, stuffy nose and crustiness of nasal secretions, and inflammation of the uveal layer of the eye. Severe disease is typically treated with a combination of immunosuppressive medications such as rituximab or cyclophosphamide and high-dose corticosteroids to control the symptoms of the disease, and azathioprine, methotrexate, or rituximab to keep the disease under control.

The number of new cases of GPA each year is estimated to be between 2.1 and 14.4 new cases per million people in Europe. GPA is rare in Japanese and African-American populations but occurs more often in people of Northern European descent. GPA is estimated to affect three cases per 100,000 people in the United States and affects men and women equally. GPA has infrequently been reported in minors.

Signs and symptoms

thumb|[[Saddle nose damage due to granulomatosis with polyangiitis is typical.]]

Initial signs are highly variable, and diagnosis can be severely delayed due to the nonspecific nature of the symptoms. In general, irritation and nasal inflammation are the first signs in most people. Typical signs and symptoms of nose or sinus involvement include crusting around the nose, stuffiness, nosebleeds, runny nose, and "saddle-nose" deformity due to a hole in the septum of the nose.) and conjunctivitis are the most common signs of GPA in the eye; involvement of the eyes is common and occurs in slightly more than half of people with the disease.

Trachea: Subglottal stenosis
Lungs: Pulmonary nodules (referred to as "coin lesions"), infiltrates (often interpreted as pneumonia), cavitary lesions, bleeding in the lungs causing a person to cough up blood, and rarely bronchial stenosis
Arthritis: Pain or swelling (60%), often initially diagnosed as rheumatoid arthritis
Skin: Subcutaneous nodules (granulomas) on the elbow, purpura, and various others (see cutaneous vasculitis)
Nervous system: Occasionally sensory neuropathy (10%) and rarely mononeuritis multiplex
Heart, gastrointestinal tract, brain, other organs: Rarely affected

Causes

The cause of GPA is unknown, although microbes, such as bacteria and viruses, as well as genetics, have been implicated in its pathogenesis.

Pathophysiology

Classic microscopic features of GPA include inflammation of blood vessels associated with poorly formed granulomas, necrosis, and many giant cells. Bacterial colonization with Staphylococcus aureus has been hypothesized as an initiating factor of the autoimmunity seen in people with GPA. it is formally classified as one of the small-vessel vasculitides in the Chapel Hill system.

Criteria

In 1990, the American College of Rheumatology accepted classification criteria for GPA. These criteria were not intended for diagnosis but for inclusion in randomized controlled trials. Two or more positive criteria have a sensitivity of 88.2% and a specificity of 92.0% of describing GPA.

thumb|221x221px|The left apical region is opacified in a case of granulomatosis with polyangiitis.

Nasal or oral inflammation with painful or painless oral ulcers or purulent or bloody nasal discharge
Lungs: Abnormal chest X-ray with nodules, infiltrates, or cavities
Kidneys: Urinary sediment with microscopic hematuria or red cell casts
Biopsy: Granulomatous inflammation within the arterial wall or in the perivascular area

thumb|right|Sclerokeratitis associated with GPA

According to the Chapel Hill Consensus Conference (CHCC) on the nomenclature of systemic vasculitis (1992), establishing the diagnosis of GPA demands

a granulomatous inflammation involving the respiratory tract, and a vasculitis of small to medium-sized vessels.

Several investigators have compared the ACR and Chapel Hill criteria.

In 2022, the American College of Rheumatology and the European Alliance of Associations for Rheumatology updated the classification criteria for GPA.

Treatment

GPA treatment depends on its severity and whether it has caused organ damage. Plasmapheresis is sometimes recommended for very severe manifestations of GPA, such as diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis (as seen in pulmonary-renal syndrome). The dose of corticosteroids is generally tapered (decreased) very slowly over several months to reduce the risk of another GPA flare. After a person with GPA has successfully undergone induction and gone into remission, the treatment goal then shifts to maintaining remission and preventing subsequent GPA flares. Less-toxic immunosuppressing medications such as rituximab, methotrexate, azathioprine, leflunomide, or mycophenolate mofetil are used. TNF inhibitors, such as etanercept, appear to be ineffective and are not recommended for routine use. Death usually resulted from uremia or respiratory failure.

Epidemiology

The incidence is 10–20 cases per million per year. It is exceedingly rare in Japan and among African Americans. Heinz Karl Ernst Klinger (born 1907) added information on the anatomical pathology. An early name for the disease was pathergic granulomatosis. The disease is still sometimes confused with lethal midline granuloma and lymphomatoid granulomatosis, both malignant lymphomas.

The full clinical picture was first presented by Friedrich Wegener (1907–1990), a German pathologist, in two reports in 1936 and 1939, leading to the eponymous name Wegener's granulomatosis or Wegener granulomatosis ().