Autoimmune rheumatic diseases: treatment in Germany

Autoimmune rheumatic diseases include the following syndromes

• autoimmune myositis;
• eosinophilic fasciitis;
• mixed connective tissue disease;
• relapsing polychondritis;
• Sjögren's syndrome;
• systemic lupus erythematosus (SLE);
• systemic sclerosis.

Rheumatoid arthritis and the various forms of seronegative spondyloarthropathies have an autoimmune aetiology. The triggers and pathophysiology of these diseases are not fully understood, but research into their pathogenesis has made it possible to develop specific treatments.

Autoimmune rheumatic diseases include the following syndromes:

• autoimmune myositis;
• eosinophilic fasciitis;
• mixed connective tissue disease;
• relapsing polychondritis;
• Sjögren's syndrome;
• systemic lupus erythematosus (SLE);
• systemic sclerosis.

Autoimmune myositis

Autoimmune myositis comprises systemic rheumatic diseases characterised by inflammatory and degenerative changes in the muscles (polymyositis) or in the muscles and the skin (dermatomyositis). Manifestations include symmetrical weakness, occasionally tenderness, and replacement of muscle by fibrous tissue, sometimes with the development of atrophy, mainly affecting the proximal muscles of the pelvic and shoulder girdles. Diagnosis is based on the clinical picture and on the assessment of muscle dysfunction by measuring the relevant enzymes, and by MRI, electromyography and muscle biopsy. Treatment uses corticosteroids in combination with immunosuppressants and/or intravenous immunoglobulin.

Autoimmune myositis can be divided into four groups:

• polymyositis
• dermatomyositis
• necrotising immune-mediated myopathies
• inclusion body myositis

Diagnosis

• clinical criteria;
• muscle biopsy (definitive).

Autoimmune myositis should be suspected in patients with weakness of the proximal muscles, with or without tenderness. Dermatomyositis should be suspected in patients with symptoms of myositis and skin lesions consistent with dermatomyositis. To establish a diagnosis of autoimmune myositis, as many as possible of the following 5 criteria must be present:

• weakness of the proximal muscles;
• characteristic rash;
• raised muscle enzyme activity (if the creatine kinase level is not elevated, a rise in aminotransferase or aldolase should be looked for, as these are less specific than CK);
• muscle abnormalities detected on electromyography or MRI;
• changes found on muscle biopsy (the definitive test)

Treatment

• corticosteroids;
• immunosuppressants (for example, methotrexate, azathioprine, mycophenolate mofetil, rituximab, tacrolimus);
• intravenous immunoglobulin (IVIG).

Eosinophilic fasciitis (EF)

Eosinophilic fasciitis is a rare disease characterised by symmetrical, painful inflammation, swelling and induration of the skin of the lower and upper limbs. The diagnosis is established by biopsy of the skin and fascia. Glucocorticoids are used for treatment. Patients develop symmetrical, painful inflammation, swelling and thickening of the arms and legs with a characteristic "orange peel" appearance.
Although the skin changes may suggest systemic sclerosis, patients with EF usually do not have Raynaud's phenomenon, involvement of the extremities, telangiectasia or changes in internal organ function (for example, impaired oesophageal motility).
To confirm the diagnosis, a deep biopsy is performed that includes the fascia and the adjacent muscle.
Treatment consists of prednisolone, immunosuppressants or a combination of the two.

The causes of eosinophilic fasciitis (EF) are unknown. It most often affects middle-aged men, but EF can also occur in women and children.

Diagnosis

• biopsy.

Prognosis

Despite mixed long-term outcomes, the eosinophil count often returns to normal after treatment.

Treatment

• oral prednisone.

Mixed connective tissue disease (MCTD)

Mixed connective tissue disease is a rare, distinct syndrome characterised by the simultaneous presence of features of SLE, systemic sclerosis and polymyositis together with very high titres of circulating antinuclear antibodies to ribonucleoprotein antigen. Typical features are swelling of the hands, Raynaud's phenomenon, polyarthralgia, inflammatory myopathy, reduced oesophageal motility and interstitial lung disease. Diagnosis is based on the clinical picture of the disease and on the detection of anti-ribonucleoprotein antibodies in the absence of antibodies characteristic of other autoimmune diseases. Treatment depends on the severity of the disease and on organ involvement and usually includes corticosteroids, which are combined with immunosuppressants.

Mixed connective tissue disease (MCTD) occurs worldwide and in people of all races, with a peak incidence in adolescence and in young adults from the age of 20. About 80% of patients are women. The cause of MCTD is unknown. In many cases the disease evolves into classic systemic sclerosis or SLE.

MCTD most often resembles SLE, systemic sclerosis and/or polymyositis. As a rule, ANA and anti-U1 RNP antibodies are present, whereas anti-Sm and anti-DNA antibodies are absent. Pulmonary hypertension should be anticipated. The disease is treated with NSAIDs or antimalarial drugs, and in more severe forms – corticosteroids and other immunosuppressants.

Diagnosis

• testing for antinuclear antibodies (ANA) to extractable nuclear antigen (antibodies to U1 ribonucleoprotein [U1-RNP]), antibodies to Smith antigen (Sm) and antibodies to DNA.

Organ involvement is determined according to the clinical findings.

Treatment

• NSAIDs and aminoquinoline drugs in mild disease;
• corticosteroids and other immunosuppressants (for example, methotrexate, azathioprine, mycophenolate mofetil) in moderate and severe disease;
• calcium channel blockers (for example, nifedipine) and phosphodiesterase inhibitors (for example, tadalafil) for Raynaud's phenomenon.

Relapsing polychondritis

Relapsing polychondritis is a rare, episodic inflammatory and destructive disease that primarily affects the cartilage of the ear and nose, but that can also involve the eyes, the tracheobronchial tree, the heart valves, the kidneys, the joints, the skin and the blood vessels. The diagnosis is established from the combined clinical, laboratory and imaging findings. In rare cases a biopsy is also required. Treatment is with prednisolone and immunosuppressants.

Relapsing polychondritis occurs with equal frequency in men and in women and usually begins in middle age. Its association with RA, systemic vasculitis, SLE and other connective tissue diseases suggests an autoimmune aetiology.

Relapsing polychondritis should be suspected if a patient has inflammation of the auricle or of the nasal cartilage, particularly with symptoms and signs typical of chondritis of the airways or of arthritis of unknown aetiology, eye inflammation, or auditory or vestibular dysfunction.
A biopsy of the affected cartilage is performed only when the diagnosis needs to be confirmed. For mild involvement of the ear, NSAIDs or dapsone are prescribed.
Treatment of more severe forms of the disease begins with corticosteroids, sometimes with methotrexate or other immunosuppressants. Avoid endotracheal intubation or, if this is not possible, be prepared for emergency cricothyrotomy.

Diagnosis

• clinical criteria;
• sometimes biopsy.

Relapsing polychondritis is diagnosed when a patient has at least 3 of the following features:

• bilateral chondritis of the auricles;
• polyarthritis;
• nasal chondritis;
• eye inflammation;
• chondritis of the respiratory tract;
• auditory or vestibular dysfunction.

A biopsy of the affected cartilage, most often of the auricle, may be useful if the diagnosis cannot be established on clinical grounds, but it is rarely required.

Prognosis

New treatments have made it possible to reduce mortality from this disease. Survival after 8 years of disease is currently 94%. The main causes of death are stenosis of the larynx and trachea, as well as cardiovascular complications such as aneurysms of the large vessels, heart valve insufficiency or systemic vasculitis.

Treatment

• NSAIDs or dapsone for mild involvement of the ear;
• corticosteroids;
• in some cases methotrexate or other immunosuppressants (for example, ciclosporin, cyclophosphamide, azathioprine, anti-TNF drugs).

Sjögren's syndrome (SS)

Sjögren's syndrome (SS) is a relatively common chronic autoimmune systemic inflammatory disease of unknown aetiology. It is characterised by dryness of the mucous membranes (including those of the mouth and the eyes) caused by lymphocytic infiltration of the exocrine glands, which impairs their function. SS can affect various exocrine glands and other organs. The diagnosis is established using specific criteria for involvement of the eyes, mouth and salivary glands, taking into account the presence of autoantibodies and, in some cases, the results of histological examination. Treatment is most often symptomatic.

SS occurs predominantly in middle-aged women. In the absence of an associated disease it is classified as primary. In addition, SS develops in approximately 30% of patients with autoimmune diseases such as RA, SLE, systemic sclerosis, mixed connective tissue disease, Hashimoto's thyroiditis, primary biliary cirrhosis or chronic autoimmune hepatitis. In these patients SS is classified as secondary. Genetic determinants of the disease have been identified (in particular, HLA-DR3 antigens in people of European descent with primary SS).

SS should be suspected in a patient with dry eyes and dry mouth, enlargement of the salivary glands, peripheral neuropathy, purpura or renal tubular acidosis of unclear origin. The diagnosis is confirmed on the basis of specific clinical criteria. Dryness symptoms should be treated symptomatically (for example, with topical moisturising agents) and factors that lead to dryness should be avoided, particularly drugs that reduce salivary gland function. In patients with serious disease (for example, severe vasculitis or involvement of the internal organs), treatment is given with corticosteroids and sometimes with other immunosuppressants.

Diagnosis

• clinical criteria;
• assessment of ocular and oral symptoms;
• examination of the lacrimal and salivary glands;
• autoantibodies;
• in some cases biopsy of the salivary glands.

Treatment

• symptomatic treatment of dryness symptoms;
• avoidance of aggravating factors;
• corticosteroids or rituximab in severe disease;
• hydroxychloroquine and/or methotrexate for musculoskeletal manifestations.

Pilocarpine orally or cevimeline HCl orally can stimulate salivary secretion, but they are contraindicated in bronchospasm and angle-closure glaucoma. Aggressive systemic treatment is sometimes indicated. In severe cryoglobulinaemic vasculitis, peripheral neuropathy/mononeuritis multiplex, marked swelling of the parotid gland, extensive lung involvement or inflammatory arthritis that does not respond to non-biological therapy, it may be necessary to use corticosteroids (for example, prednisone 1 mg/kg orally once a day) or rituximab.

Systemic lupus erythematosus (SLE)

Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory disease of autoimmune origin; it mainly affects young women. The disease most often presents with arthralgia and arthritis, Raynaud's phenomenon, malar and other rashes, pleurisy or pericarditis, involvement of the kidneys or the CNS, and haematological cytopenias. The diagnosis is established from the clinical manifestations and the results of serological tests. A severe active phase of the disease requires corticosteroids and, in some cases, immunosuppressants.

Women make up 70–90% of the total number of patients (mainly of reproductive age). SLE is more common in Black and Asian people than in white people. Nevertheless, SLE can be diagnosed at any age, even in newborns. In some countries the prevalence of SLE rivals that of RA. SLE may be caused by as yet unknown environmental triggers that set off autoimmune reactions in genetically predisposed individuals. Certain drugs (in particular, hydralazine and procainamide) can cause a lupus-like syndrome.

Forms of lupus

• discoid lupus erythematosus (DLE);
• subacute cutaneous lupus erythematosus (SCLE).

Clinical manifestations

• fever;
• episodes of arthralgia and malaise;
• headaches, seizures or psychosis;
• joint manifestations (from arthralgia to acute polyarthritis);
• fibromyalgia;
• signs of involvement of the skin and mucous membranes ("butterfly" erythema over the cheekbones; erythematous, firm, maculopapular skin lesions on the face and neck, over the upper chest and the elbows; bullous changes and ulceration of the mucous membranes; generalised or patchy alopecia; subcutaneous nodular lesions, migrating erythema of the hands and fingers, necrosis of the nail bed, urticaria, palpable purpura; petechiae associated with thrombocytopenia; photosensitivity; pink to violet plaques or nodules; lesions resembling lichen planus;
• cardiopulmonary manifestations;
• lymphadenopathy and changes in the spleen;
• neurological manifestations;
• involvement of the kidneys;
• obstetric complications;
• haematological manifestations;
• gastrointestinal manifestations.

Diagnosis

• clinical criteria;
• cytopenias;
• autoantibodies.

Laboratory testing makes it possible to distinguish SLE from other connective tissue diseases and includes the following:

• antinuclear antibodies (ANA) and antibodies to double-stranded (ds) DNA;
• full blood count;
• urinalysis;
• biochemistry: measurement of the renal and liver enzymes.

Treatment

• hydroxychloroquine for all patients with SLE;
• NSAIDs and often aminoquinoline drugs in mild disease;
• glucocorticoids and immunosuppressants in severe disease.

To make the principles of treatment easier to understand, the course of SLE can be classified as mild (for example, fever, arthritis, pleurisy, pericarditis, headache, rash) and severe (for example, haemolytic anaemia, thrombocytopenic purpura, massive involvement of the pleura and pericardium, marked impairment of renal function, acute vasculitis of the limbs or of the gastrointestinal tract, significant CNS involvement, diffuse alveolar haemorrhage).

The antimalarial drug hydroxychloroquine is indicated for all patients with SLE regardless of the severity of the disease, because it reduces the frequency of flares and lowers mortality; however, hydroxychloroquine is not used in patients with G6PD deficiency, as it can cause haemolysis.

Systemic sclerosis

Systemic sclerosis is a rare chronic disease of unknown aetiology characterised by the development of diffuse fibrosis and by pathological changes in the vessels of the skin, the joints and the internal organs (particularly the oesophagus, the lower gastrointestinal tract, the lungs, the heart and the kidneys). Typical symptoms include Raynaud's phenomenon, polyarthralgia, dysphagia, heartburn, swelling and, ultimately, marked thickening of the skin and contracture of the fingers. The main causes of death are involvement of the lungs, heart and kidneys. Diagnosis is based on the clinical picture, but laboratory tests can help to confirm the diagnosis and assist with prognosis. Specific treatment is difficult, and management often consists of treating the complications.

Systemic sclerosis (SSc) is approximately 4 times more common in women than in men. It most often manifests at the age of 20–50 years and is rare in children.

Classification of SSc

• limited SSc (CREST syndrome);
• generalised SSc (with diffuse skin involvement);
• SSc without skin involvement.

In limited SSc (CREST syndrome—calcinosis of the skin, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia) patients develop tightening of the skin of the face and distal to the elbows and knees, and gastro-oesophageal reflux disease may also be seen. This type is characterised by slow progression and is often complicated by pulmonary hypertension.

In generalised SSc with diffuse skin involvement, patients have Raynaud's phenomenon and complications affecting the gastrointestinal tract. This type usually develops rapidly. The main complications are interstitial lung disease and scleroderma renal crisis.

Clinical manifestations

The most common initial manifestations of systemic sclerosis are Raynaud's phenomenon and gradually developing swelling of the distal parts of the limbs with thickening of the skin of the fingers. Marked polyarthralgia is also noted. Sometimes the first manifestations of the disease may be gastrointestinal problems (for example, heartburn, dysphagia) or respiratory problems (dyspnoea).

• involvement of the skin and nails;
• joint manifestations;
• gastrointestinal manifestations;
• cardiopulmonary manifestations;
• involvement of the kidneys.

Diagnosis

• clinical criteria
• antibody testing

The standard criteria for systemic sclerosis include the following:

• thickening of the skin of the fingers of both hands;
• lesions of the fingertips (for example, ulcers, pitting scars);
• telangiectasia;
• abnormal nailfold capillaries (for example, ectatic blood vessels, vessel dropout);
• pulmonary arterial hypertension and/or interstitial lung disease;
  Raynaud's phenomenon;
• SSc-related autoantibodies (anticentromere antibodies, anti-Scl-70, anti-RNA polymerase III).

Treatment

• symptomatic treatment and correction of functional impairment

No drug has a substantial effect on the overall course of SSc, but principles have been established for the drug treatment of individual patterns of organ and body-system involvement. Corticosteroids may be effective in myositis and mixed connective tissue disease; however, they may predispose to renal crisis and should therefore be used only when strictly necessary. In pulmonary alveolitis it is possible to use immunosuppressants, including methotrexate, azathioprine, mycophenolate mofetil and cyclophosphamide. Mycophenolate mofetil is effective in the treatment of interstitial lung disease. There are reports of successful lung transplantation. In pulmonary hypertension it is appropriate to prescribe epoprostenol (prostacyclin) and bosentan. Calcium channel blockers such as nifedipine taken orally are effective in Raynaud's phenomenon. Bosentan, sildenafil, tadalafil, vardenafil and other alternative drugs are used for the treatment of severe Raynaud's phenomenon. For ischaemia of the fingers, intravenous infusions of prostaglandin E1 (alprostadil), epoprostenol or sympathetic blockers are given.

If an acute renal crisis develops, which is an emergency, adequate therapy with ACE inhibitors must be given. Recent evidence has shown that autologous haematopoietic stem cell transplantation in early generalised SSc increases survival beyond the first year more than intravenous cyclophosphamide; however, mortality during the first year was higher. In the future this may become an option for certain patients.

Rheumatoid arthritis (RA)

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the joints. The pathological changes in RA are mediated by cytokines, chemokines and metalloproteinases. It is characterised by inflammation of symmetrical peripheral joints (for example, the wrist joints and the metacarpophalangeal joints), leading to progressive destruction of the joint structures; signs of systemic involvement are also seen. Diagnosis is based on specific clinical manifestations and on laboratory and radiological findings. Treatment uses drugs, physiotherapy and, in some cases, surgical methods. Disease-modifying antirheumatic drugs make it possible to control the symptoms and slow the progression of the disease.

RA occurs in approximately 1% of the population. The incidence in women is 2–3 times higher than in men. The disease can develop at any age, most often between 35 and 50 years, but it can also occur in childhood (see Juvenile idiopathic arthritis) and in older people.

Clinical manifestations

Rheumatoid arthritis usually begins gradually, often starting with general and joint symptoms. General features include morning stiffness in the affected joints, general fatigue and malaise, loss of appetite, general weakness and, in some cases, a low-grade fever. Joint symptoms include pain, swelling and stiffness. Sometimes the disease begins suddenly, mimicking an acute viral illness.

The disease progresses most rapidly during the first 6 years, especially in the 1st year; in 80% of patients irreversible joint changes develop within 10 years. The course of the disease in an individual patient is unpredictable.

Symmetrical involvement of the joints is typical. Stiffness is usually noted in the morning after waking and lasts more than 60 minutes, but it can also be seen after a prolonged period of rest (the so-called "gel phenomenon"). The affected joints become painful, with redness, swelling and increased warmth of the tissues over the joint, and with restricted movement.

Joint manifestations affect:

• the wrist joints and the metacarpophalangeal joints of the index (2nd) and middle (3rd) fingers (most commonly affected);
• the proximal interphalangeal joints;
• the metatarsophalangeal joints;
• the shoulder joints;
• the elbow joints;
• the hip joints;
• the knee joints;
• the ankle joints.

Extra-articular manifestations

• subcutaneous rheumatoid nodules;
• vasculitis causing ulcers of the lower limbs or mononeuritis multiplex;
• pleural or pericardial effusion;
• infiltrates or fibrosis in the lungs;
• pericarditis;
• myocarditis;
• lymphadenopathy;
• Felty's syndrome;
• Sjögren's syndrome;
• scleromalacia;
• episcleritis.

Diagnosis

• clinical criteria;
• rheumatoid factor (RF), anti-CCP, and ESR or C-reactive protein (CRP);
• radiography.

Differential diagnosis

Many conditions can resemble RA:

• crystal-induced arthritis;
• systemic lupus erythematosus (SLE);
• sarcoidosis;
• reactive arthritis;
• psoriatic arthritis;
• ankylosing spondylitis;
• arthritis associated with hepatitis C;
• osteoarthritis.

Prognosis

RA shortens life expectancy by 3–7 years; the increased mortality is due to heart disease, infections and gastrointestinal bleeding; drug therapy, comorbidities and the development of malignant tumours can also have a negative effect.

Treatment

• supportive measures (for example, stopping smoking, nutrition, rest, physical treatments, analgesics);
• drugs that slow the progression of the disease;
• if required: NSAIDs for the relief of pain;

Treatment of RA involves a balanced combination of rest and physical activity, appropriate nutrition, exercise, drug therapy and sometimes surgery.

Drugs for the treatment of rheumatoid arthritis

Disease-modifying antirheumatic drugs (DMARDs) are prescribed early, often in combination. Other classes of drug, including biological agents such as TNF-alpha antagonists, IL-1 receptor inhibitors, IL-6 blockers, B-cell-depleting agents, T-cell co-stimulation modulators and Janus kinase (JAK) inhibitors, also slow the progression of RA. NSAIDs help to reduce pain in RA to some extent, but they do not prevent the development of erosions or the progression of the disease and they increase the risk of cardiovascular disease, so they should be used only as adjunctive therapy. To control severe polyarticular symptoms, low-dose systemic corticosteroids (prednisolone < 10 mg once a day) may be added, usually with subsequent switching to a DMARD.

The optimal combination of drugs has not yet been determined. An example of initial therapy is:

• methotrexate 7.5 mg orally once a week (with folic acid 1 mg orally once a day);
• if the drug is well tolerated but ineffective, the methotrexate dose is increased at intervals of 3–5 weeks up to a maximum of 25 mg orally or by injection once a week;
• if there is no adequate response, a biological agent should be added; as an alternative, the optimal approach is triple therapy with methotrexate, hydroxychloroquine and sulfasalazine. Leflunomide can be used instead of methotrexate, or it can be added to methotrexate with careful monitoring of liver function tests and the full blood count.

NSAIDs

• aspirin;
• ibuprofen;
• diclofenac.

Conventional disease-modifying antirheumatic drugs (DMARDs)

• methotrexate;
• hydroxychloroquine;
• sulfasalazine;
• leflunomide;

Corticosteroids

Intra-articular injections of depot glucocorticoids

• triamcinolone hexacetonide;
• triamcinolone acetonide;
• methylprednisolone acetate.

Immunomodulatory, cytotoxic and immunosuppressive drugs

• azathioprine;
• ciclosporin.

Genetically engineered biological agents

• rituximab;
• abatacept;
• anakinra;
• TNF-alpha antagonists (adalimumab, etanercept, etanercept-szzs, golimumab, certolizumab pegol, infliximab and infliximab-dyyb);
• sarilumab;
• tocilizumab;
• baricitinib ;
• tofacitinib.

The seronegative spondyloarthropathies (seronegative spondyloarthritides) share a number of common clinical features (for example, back pain, the development of uveitis, gastrointestinal symptoms and skin rashes). Some are associated with carriage of HLA-B27. Their clinical and genetic similarities suggest that they have similar causes or pathogenesis. In the spondyloarthropathies, rheumatoid factor (RF) is usually not detected, which is why they are also called seronegative spondyloarthropathies. This group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis and other conditions.

Spondyloarthropathies may develop in association with gastrointestinal disorders (sometimes called enteropathic arthritis), in particular in inflammatory bowel disease, small bowel bypass surgery or Whipple's disease.

Juvenile spondyloarthropathy is asymmetrical, mainly affects the lower limbs and usually begins between the ages of 7 and 16.

Spondyloarthropathy can also develop in patients without the specific features characteristic of a defined spondyloarthropathy (undifferentiated spondyloarthropathy). The principles of treating arthritis in other patients with spondyloarthritis are identical to those used in the treatment of reactive arthritis.

Ankylosing spondylitis

Ankylosing spondylitis is the prototype of the spondyloarthropathies and is a systemic disease characterised by inflammation of the axial skeleton, the large peripheral joints and the digits, night-time back pain, stiffness of the back, marked kyphosis, aortitis, conduction disturbances and anterior uveitis. Radiological evidence of sacroiliitis is required to confirm the diagnosis. Treatment uses NSAIDs and/or tumour necrosis factor inhibitors or IL-17 antagonists, together with therapeutic exercise that improves joint mobility. Ankylosing spondylitis is 3 times more common in men than in women and most often begins between the ages of 20 and 40

Classification

• axial ankylosing spondylitis: mainly affects the axial parts of the skeleton, and radiographs show features typical of sacroiliitis;
• non-radiographic ankylosing spondylitis: clinically similar to axial ankylosing spondylitis, but without the radiographic findings typical of sacroiliitis;
• peripheral ankylosing spondylitis: ankylosing spondylitis that mainly affects the peripheral parts of the skeleton.

Diagnosis

• radiography of the lumbosacral spine and the sacroiliac joint;
• blood tests (ESR, C-reactive protein, HLA-B27 and full blood count) or clear clinical criteria;
• MRI of the pelvic region of the spine in some patients.

Treatment

• NSAIDs;
• sulfasalazine, methotrexate, TNF-alpha antagonists or IL-17 antagonists (for example, etanercept, infliximab, adalimumab, certolizumab, golimumab);
• therapeutic exercise and supportive measures.

Vasculitides

Vasculitis is inflammation of the blood vessels, the connective tissue and the internal organs. Vasculitis can involve blood vessels of any type: arteries, arterioles, veins, venules and capillaries. The clinical manifestations of the disease process in vasculitis are varied and depend on the size and location of the affected vessels, on the degree of organ involvement, and on the extent and nature of the inflammation.

Aetiology

Vasculitis may be

• primary
• secondary

The cause of primary vasculitis is unknown. Secondary vasculitis may be caused by infection, by the use of drugs or by exposure to toxins, or it may occur as part of another inflammatory or malignant disease.

Classification of the vasculitides

• Behçet's disease;
• cutaneous vasculitis;
• eosinophilic granulomatosis with polyangiitis (Wegener's granulomatosis);
• giant cell arteritis;
• granulomatosis with polyangiitis;
• haemorrhagic vasculitis (immunoglobulin A-associated vasculitis);
• microscopic polyangiitis:
• polyarteritis nodosa;
• urticarial vasculitis;
• Horton's disease / polymyalgia rheumatica;
• cryoglobulinaemic vasculitis;
• Takayasu arteritis;
• Winiwarter-Buerger syndrome;
• Ormond's syndrome;
• Henoch-Schönlein purpura.

Diagnosis

• clinical assessment;
• basic laboratory tests to detect inflammation or organ dysfunction (for example, full blood count, ESR or C-reactive protein, serum albumin and total protein, AST and ALT, urea nitrogen and creatinine, urinalysis) and to determine the stage of the disease;
• laboratory tests that help to determine the type of vasculitis (for example, antineutrophil cytoplasmic antibodies [ANCA]), if these are indicated by the results of the clinical assessment;
• laboratory tests and imaging methods that can help to determine the aetiology of the vasculitis (for example, cryoglobulins, viral hepatitis) and the extent of organ involvement;
• biopsy.

Treatment

• induction of remission in vasculitis that threatens life or an organ, using corticosteroids, often in combination with cyclophosphamide or rituximab (corticosteroids, cyclophosphamide, mesna, rituximab);
• for the induction of remission in less severe forms of vasculitis, a combination of corticosteroids and less potent immunosuppressants (for example, methotrexate, azathioprine, mycophenolate mofetil) or rituximab may be used;
• remission is maintained with methotrexate, azathioprine or rituximab plus gradual tapering of the corticosteroid dose;