The illness initially presents with a prodromal phase characterized by fever, myalgia, arthralgia, and weight loss. The manifestations that follow are reflective of which systems are affected. The kidneys are involved in as many as 90% of all patients. Hematuria is one of the common signs. Kidney disease can rapidly evolve into renal failure. Individuals with gastrointestinal (GI) disease exhibit nausea, emesis, diarrhea, abdominal pain, and bloody stools.

Additionally, vasculitis of the lungs may result in alveolar hemorrhage and pulmonary fibrosis. The former is typified by a sudden onset of dyspnea and is possibly accompanied by hemoptysis. Other symptoms of the respiratory disease are rhinitis, sinusitis, and epistaxis. Patients with neurologic sequelae experience mononeuritis multiplex, which affects peripheral or cranial nerves. Furthermore, severe complications may include stroke or seizures.

Approximately one-third of individuals have vasculitis of the skin, which results in purpura rash, and possibly splinter hemorrhages. Finally, episcleritis arises in ocular vasculitis.

Individuals suspected to have vasculitis should be immediately evaluated with a detailed personal and family history, a physical exam, and comprehensive testing.

Laboratory tests

There are various potential findings in patients with MPA. For example, 80% are positive for ANCA, 60% for perinuclear ANCA (PANCA), and 40% for cytoplasmic ANCA (CANCA). Also, C3 and C4 complement studies are normal. Additional studies reveal leukocytosis and normocytic anemia on CBC and elevated ESR. Kidney function tests demonstrate increased blood urea nitrogen (BUN) and serum creatinine levels in 70% of patients, proteinuria in 80%, hematuria in almost 70%, and leukocyturia in 40%. Other results include the presence of erythrocyte casts and abnormal urine sediment. Note that blood cultures should be obtained to investigate bacterial endocarditis.

Imaging

The selection of imaging modalities is based on the present symptoms and complications. For example, patients with respiratory involvement should have a chest radiograph. This study typically displays bilateral nodular and patchy opacities, cavitary lesions, and parenchymal infiltrates. Furthermore, computed tomography (CT) and gastrointestinal endoscopy should be obtained for abdominal manifestations such as bleeding. Electromyography (EMG) is indicated in neuropathy while electrocardiography (ECG) is warranted for the evaluation of cardiac disease.

Other

Biopsies are performed for involved sites such as the skin, lungs, kidneys. and sural nerve. A muscle biopsy may be considered as well whether or not there is myalgia or other evidence of muscle involvement [10].

The treatment of MPA is centered on remission induction and maintenance.

Remission induction

Since glomerulonephritis is a common manifestation in patients with MPA, historically the regimen consisted of cyclophosphamide and glucocorticoids for both induction and maintenance [11]. However, cyclophosphamide is associated with serious adverse effects such as malignancy, hemorrhagic cystitis, and infertility [12]. Therefore, researchers sought to minimize the use of this toxic medication.

Currently, there are numerous approaches for the initiation of therapy. One method is to avoid cytotoxic drugs if possible. Hence, patients with mild to moderate renal disease may be spared the use of cyclophosphamide and require only glucocorticoids and mycophenolate mofetil [13]. Additional options include methotrexate [14] and leflunomide [15].

Another drug that represents an alternative to cyclophosphamide is rituximab. One trial compared the two medications [16] and observed that the six-month remission rate for rituximab was 63.6% in comparison to 53.1% with cyclophosphamide. Also, patients who continued taking low-dose glucocorticoids in conjunction with the respective medications had better remission rates. Also, rituximab offers a promising treatment for those with relapsing disease.

Remission maintenance

One trial investigated cyclophosphamide versus azathioprine for the management of the remission maintenance phase [17]. Prior to the treatment with one of these two agents, all patients received cyclophosphamide and prednisolone for remission induction. The relapse rate was similar in both groups, which was 15% in the cyclophosphamide patients and 10% in the azathioprine. The study notably reports that induction with cyclophosphamide and maintenance with azathioprine is as effective as prolonged therapy with cyclophosphamide.

Another trial evaluated the outcomes of maintenance therapy with methotrexate versus azathioprine after induction with cyclophosphamide [18]. The relapse rate was similar: 33% in the methotrexate group versus 36% in the azathioprine group.

Other

Additional therapies may be beneficial for patients with MPA. For example, plasma exchange has been compared with methylprednisolone as adjunctive agents. The study discovered that plasma exchange decreased the development of end-stage renal disease at the 12-month mark [19] although both groups had equal mortality rates.

Factors such as older age, the severity at onset, number of relapses, and the length of glucocorticoid therapy were correlated to long-term organ damage [8]. Also, according to one investigation, pulmonary involvement was associated with a greater risk for multisystem diseases affecting the heart and kidney [9].

Fortunately, treatment accounts for an improvement in 90% of affected individuals. Moreover, 75% of patients enter remission although 30% experience a recurrence in a year or two.

The survival rate at five years is about 75%. However, two of the leading causes of morbidity and death are necrotizing glomerulitis and hemorrhagic pulmonary capillaritis. Note that MPA has worse outcomes than some of the other vasculitis diseases.

While the exact etiology is unknown, the cause is likely multifactorial in origin consisting of genetic and environmental interplay. Patients often have a positive family history of other autoimmune diseases.

MPA has been associated with the use of drugs such as propylthiouracil, penicillamine, and hydralazine. Additionally, silica exposure is another environmental factor related to the etiology of the disease.

The incidence of this disease is estimated to be 1 in a population of 100,000. With regards to patient demographics, the average age of onset is 50 years. Also, there is a slight predilection for males [2] [3] [4].

While the pathophysiology is not well-elucidated, there is a theory that ANCA may be implicated in the development of MPA. Specifically, researchers speculate that primed neutrophils expressing myeloperoxidase (MPO) adhere to the endothelium of blood vessels and/or glomeruli and subsequently become activated by interacting with MPO-ANCA [5]. Furthermore, animal studies have reported that MPO-ANCA plays a role in glomerulonephritis and pulmonary capillaritis [6] [7].

It is important to note, however, that not all patients with MPA are ANCA positive. This suggests that there are other mechanisms that contribute to the pathogenesis of MPA. Very importantly, it is likely that this disease develops in genetically predisposed individuals.

Histopathology

The histologic analysis may help to differentiate MPA from polyarteritis nodosa and small vessel vasculitis as MPA affects the venules, arterioles, and capillaries. Moreover, the walls of these smaller vessels may contain neutrophilic infiltration.

Findings indicative of glomerulitis include focal necrosis, crescent formation, and the absence of immunoglobulin. Evaluation of the lung tissue demonstrates alveolar capillaritis while the muscle and sural nerve likely exhibit necrotizing vasculitis.

This disease cannot be prevented. However, early diagnosis and treatment can improve outcomes.

Microscopic polyangiitis (MPA) is described as systemic vasculitis that is associated with antineutrophil cytoplasmic antibody (ANCA). This inflammatory disease affects small blood vessels such as the capillaries of the lungs, kidneys, and other organs. While the etiology and pathophysiology are not fully understood, evidence points to the likelihood of genetic predisposition and environmental components. While ANCA is positive in the majority of patients, there are likely other pathogenic mechanisms. Note that there are similar vasculitides associated with ANCA such as granulomatosis with polyangiitis (previously named Wegener granulomatosis) among others [1].

MPA can involve numerous organs, thereby producing a wide spectrum of symptoms. It mainly affects the renal and pulmonary blood vessels. It can cause life-threatening complications such as necrotizing glomerulitis and diffuse alveolar hemorrhage.

Clinical assessment is comprised of the patient and family history, physical examination, and the appropriate tests. The latter includes ANCA studies, complete blood count (CBC), erythrocyte sedimentation rate (ESR), and urinalysis. Furthermore, biopsies of affected organs are obtained. Finally, imaging techniques are performed to evaluate the present manifestations.

The treatment focuses on two key phases, which are remission induction and remission maintenance. Numerous drug trials have been conducted to determine the most effective treatment regimens based on renal involvement, the severity of the overall disease, and other factors. The first phase can be treated with cyclophosphamide and glucocorticosteroids, or with rituximab. The maintenance program can utilize cyclophosphamide, azathioprine, or methotrexate. Since cyclophosphamide is associated with severe side effects, its use should be minimized as much as possible.

Due to the risk of morbidity and mortality associated with MPA, prompt recognition and treatment are paramount in these patients. Aggressive management is typically necessary to prevent organ damage and other severe outcomes.

What is microscopic polyangiitis (MPA)?

This is a rare disease that results from vasculitis, which is inflammation of the blood vessels. MPA can involve various organs such as the kidneys, skin, and lungs. It can cause severe damage to these organs.

What are the causes?

The cause of MPA has not been discovered yet. It is thought that the disease develops due to genetic and environmental factors.

There are ANCA antibodies in the majority of individuals that are affected with this disease. These antibodies attach to certain types of white blood cells, which in turn attach to the walls of blood vessels. This whole process leads to the secretion of substances that cause inflammation.

What are the signs and symptoms?

This disease can affect many organs and organ systems. Therefore, patients can have a wide spectrum of signs and symptoms. Initially, they have:

• Fatigue
• Fever
• Weight loss
• Loss of appetite

The following symptoms may develop:

• Skin: rash with reddish-purple spots
• Abdominal: nausea, vomiting, diarrhea, abdominal pain, and bloody stools
• Kidney: blood in urine
• Lung: shortness of breath, coughing with blood, nosebleeds, sinusitis
• Muscle: loss of strength
• Nerve: abnormal sensation and numbness

Complications may include:

• Kidney failure
• Severe lung disease
• Seizures
• Stroke
• Others

How is it diagnosed?

When an individual presents with the above symptoms, the clinician will obtain the patient and family history, perform a physical exam, and order the appropriate blood tests such as:

• ANCA antibodies
• Complete blood cell count
• Erythrocyte sedimentation rate
• Creatinine
• Urinalysis

Imaging tests are performed depending on which symptoms are present:

• Chest x-ray
• CT scan of affected organs
• Gastrointestinal endoscopy
• Electromyography (EMG)
• Electrocardiography (ECG)

Biopsy (sample tissue) of affected organs is also obtained.

How is it treated?

The treatment is administered into two main phases which are remission induction and remission maintenance:

• Induction: cyclophosphamide and high-dose corticosteroids, or rituximab
• Maintenance: cyclophosphamide, azathioprine, or methotrexate
• Additional medications: glucocorticosteroids, plasma exchange

The treatment regimen depends on the kidney function, how severe the disease is, and other important factors. A combination of medications is typically given.

Can it be prevented?

There is no way to prevent the development of MPA. However, early treatment can help prevent complications.

What is the prognosis?

Treatment significantly improves the outcome in the majority of patients. Also, many patients achieve full remission although some relapse.

It is very important that patients are diagnosed and treated as soon as possible in order to prevent organ damage and complications.

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