Seminars for the 5th year
Internal medicine
Prof. Jiří Horák
RHEUMATOLOGY 2
THE SPONDYLARTHROPATHIES
Group of disorders that share a constellation of clinical, radiographic, and
immunogenetic manifestations:
 Axial arthritis (sacroileitis, spondylitis)
 Peripheral arthritis
 Enthesitis
 Presence of the MHC antigen HLA-B27
Ankylosing spondylitis (Bechterew’s disease)
Prevalence 0.02 – 0.23%. It mostly affects young males (male:female ratio 2.5 –
5:1).
Sy: insidious onset of low-back pain or stiffness. Hallmark – symmetrical
sacroileiitis. Constitutional features – fever, anorexia, weight loss. The cervical
spine is involved late in the disease.
Peripheral asymmetrical oligoarthropathy in 30% (hips, ankles, shoulders,
elbows, small joints of hands and feet).
Extra-articular disease:
 ocular involvement in up to 40% - uveitis.
 aortitis, aortic insufficiency, mitral valve disease, pulmonary
fibrosis,amyloidosis
Physical findings: diminished chest expansion (< 4 cm), Schober test < 14 cm.
Lab: ↑ ESR and CRP, anemia of chronic disease, HLA-B27 +.
Radiographs: before the onset of ankylosis – normal mineralization, later
generalized osteoporosis, sacroileiitis, calcification of spinal ligaments –
“bamboo spine”.
Course: variable, earlier age – more severe outcome.
Complications: restrictive lung disease, cauda equina syndrome, osteoporotic
compression fractures.
Reiter’s syndrome
Example of reactive arthritis.
Triad: arthritis, urethritis, conjunctivitis is seen in only 33% of patients.
Peak onset in the 3rd decade.
Genitourinary tract involvement: dysuria, urethral discharge, prostatitis in men,
cervicitis or vaginitis in women.
Fever, malaise, weight loss, fatigue, anorexia.
Arthritis – often the last feature to appear: lower extremities – first
metatarsophalangeal joints, ankles, knees, toes). With chronicity, upper
extremity involvement may occur.
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Seminars for the 5th year
Internal medicine
Prof. Jiří Horák
Low back pain in up to 50% patients.
Radiographic evidence of axial or sacroiliac involvement is present only with
chronic or severe disease. About 29% of most severely affected patients
demonstrate radiographic sacroileitis. Soft-tissue swelling (sausage digits).
Extra-articular manifestations: enthesitis – Achilles tendon or plantar fascia;
mucocutaneous features – urethritis, balanitis, cervicitis, vaginitis, painless
palatal or lingual ulcerations; keratoderma blenorrhagicum on the soles or
palms; ocular manifestations – conjunctivitis, uveitis, rarely keratitis.
Course: an initial episode lasting 2 – 3 months, recurrent attacks and diseasefree intervals are common. Chronic peripheral arhropathy in 20 – 50% of
patients. Death is rare.
Reactive arthritis
Acute, sterile, non-suppurative arthropathy arising after an infectious process
but at a site remote from the primary infection (Shigella, Salmonella, Yersinia,
Campylobacter, Chlamydia).
Clin: asymmetrical oligoarthritis.
Psoriatic arthritis
In 5 – 7% of patients with cutaneous psoriasis.
Clin: an insidious onset, progressive course.
Soft-tissue swelling (sausage digits).
Enteropathic arthropathies
- associated with Crohn’s disease or ulcerative colitis.
Treatment of spondyloarthropathies
Aimed at reducing pain and stiffness.
– Program of exercise, rest, physical therapy;
– NSAIDs are the mainstay of therapy (not in enteropathic arthropathies) –
indomethacin, diclophenac, napoxen, sulindac;
– corticosteroids – used by intraarticular injection;
– antibiotics – in Reiter’ syndrome or infectious diarrhea;
– slow-acting antirheumatic drugs (methotrexate, sulfasalazine) – if
NSAIDs fail to control symptoms;
– surgery – total joint replacement
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Seminars for the 5th year
Internal medicine
Prof. Jiří Horák
Systemic sclerosis (scleroderma)
Systemic disease that targets the skin, lungs, heart, GIT, kidneys, and
musculoskeletal system.
Features: a) tissue fibrosis, b) small blood vessel vasculopathy, c) autoimmune
response associated with autoantibodies.
Scleroderma: limited or diffuse
Diffuse scleroderma:
 widespread skin thickening involving distal and proximal body
 rapid onset following appearance of Raynaud’s phenomenon
 visceral involvement (lungs, heart, GIT, kidney)
 associated with ANA
 10-year survival 40 – 60%
CREST syndrome (a variant of limited scleroderma): subcutaneous calcinosis,
Raynaud’s phenomenon, esophageal dysfunction, sclerodactyly and
teleangiectasia – usually a more benign course.
Overlap syndromes – frequently include findings suggestive of scleroderma:
MCTD – Mixed Connective Tissue Disease – scleroderma, polymyositis, lupuslike rashes, rheumatoid-like polyarthritis.
Prevalence: 10 – 30/100,000 inhabitants
Incidence: 2/100,000 inhabitants/year
Female-to-male ratio 3 to 7:1
Natural history: a chronic disease that evolves over months or years.
Scleroderma rarely relapses after remitting.
Pathogenesis: vasculopathy of small and medium arteries
Vascular
perturbation
Genetic
Environmental
Infection
Tissue fibrosis
Autoimmunity
300-fold increase in alpha-2 adrenergic smooth muscle activity.
Endothelial cell dysfunction. Widespread microvascular dysfunction → digital
ischemia + reperfusion damage → cutaneous ulcers or digital amputation
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Seminars for the 5th year
Internal medicine
Prof. Jiří Horák
Episodic vasospasm of endomyocardial vessels → contraction-band necrosis or
focal fibrosis → arrhythmia or cardiomyopathy
Vasospasm of the small arteries of the kidney → hypertension, renal infarction,
or renal failure
Activated T cells, macrophages, mast, cells, or platelets → profibrotic cytokines
(TGF-beta, platelet-derived growth factor, interleukin-1, endothelin-1) →
activated tissue fibroblasts → excessive production of collagen and other
extracellular molecules → tissue fibrosis
Autoimmunity: antibodies against topoisomerase and RNA-polymerases.
Clinical manifestations
 Raynaud’s phenomenon and digital ischemia
 Skin involvement - cutaneous fibrosis
o Edematous phase (pruritus)
o Fibrotic stage
o Atrophy, contractures, skin ulcerations
o Masked facies, small oral apertures, vertical furrowing of the perioral skin
 GIT involvement
o Decreased facial flexibility → difficult chewing
o Esophageal disease in 90% of patients – heartburn, dysphagia,
reflux esophagitis (proton-pump inhibitors)
o Dysmotility of the small and large bowel → intestinal
pseudoobstruction
o Large-mouth diverticula
o Fibrosis of anal sphincters → incontinence of stools
 Pulmonary involvement - the leading cause of mortality in scleroderma
o Fibrosing alveolitis → restrictive lung disease (low diffusing
capacity, reduced lung volume) – diagnosis of activity from
bronchoalveolar lavage fluid – Th: cyclophosphamide + steroids
o Obliterative vasculopathy of medium and small pulmonary vessels
→ pulmonary hypertension
o Clin: dyspnea in the absence of chest pain
o Activity can be defined by lavage of bronchoalveolar fluid (BAL)
o In some patients, pulmonary hypertension develops – either
primary (without interstitial lung disease) or secondary – Th:
calcium-channel blockers
 Cardiac involvement
o Pericardial effusion
o Arrhythmias
o Acute pericarditis
o Myocardial fibrosis → cardiomyopathy and heart failure
o Myocarditis
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Seminars for the 5th year
Internal medicine
Prof. Jiří Horák
 Renal involvement
o Before the discovery of ACE inhibitors, hypertensive renal crisis
was the leading cause of death in scleroderma, which is now rare
o Mild proteinuria or microscopic hematuria are now the most
common signs of renal disease
o ~ 10% of patients with diffuse scleroderma have a renal crisis that
mimics malignant hypertension (together with microangiopathic
hemolytic anemia, thrombocytopenia, and rapidly progressive loss
of renal function
o Th: ACE inhibitors
 Musculoskeletal involvement
o Pain, stiffness
o Sense of weakness
o Tendon friction rubs
o Skin fibrosis can extend into the striated muscle
 Diagnosis and differential diagnosis
o At the onset, often “undifferentiated connective tissue disease” is
diagnosed
o Raynaud’s phenomenon
o DD: - eosinophilic fasciitis (progressive stiffening of the arme, legs
and trunk)
 Scleromyxedema (+ IgG paraproteinemia)
 Treatment: no treatment has proved safe and effective
o D-penicillamine – not effective
o Methotrexate – may control inflammation but it is not known if it
prevents sclerosis
 Prognosis
o 5-year survival >80%
o 10-year survival 60%
 Dermatomyositis and polymyositis
o Both occur more frequently in females
o Onset of symmetrical proximal muscle weakness subacutely over
weeks or several months
o Pathogenesis
of
dermatomyositis:
humorally
mediated
microangiopathy → ischemic damage of muscle fibers
o Pathogenesis of polymyositis: HLA-restricted, antigen-specific,
cell-mediated immune response directed against muscle fibers. The
antigen is not known.
o Dermatomyositis can present in children or adults
o Polymyositis is an adult disorder
o Dermatomyositis
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Seminars for the 5th year
Internal medicine
Prof. Jiří Horák
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at the onset a heliotropic rash (eyelids, periorbital edema)
Subcutaneous calcifications can be very painful
V-sign (macular rash on the face, neck and anterior chest)
Periungual erythema
Inclusion body myositis - an insidious onset of proximal and
distal muscle weakness – the most common inflammatory
myopathy in the elderly
Associated manifestations
 Cardiac involvement → congestive heart failure
 Interstitial lung disease
 Arhtralgias
 An increased incidence of malignancy (lung, breast, ovary,
GIT, myeloproliferative disorders)
Laboratory features
 EMG
 Increased serum CK
 ESR is usually normal
 ANA may be positive
 A muscle biopsy should be performed in suspected myopathy
Treatment
 Inclusion body myositis is usually refractory to
immunosuppressive therapy
 Dermatomyositis and polymyositis:
 Prednisone – starting dose 1-2 mg/kg/day, after 2 – 4
weeks reduction of dose
 Most patients require therapy for many years
 Calcium + vitamin D should be added
 Second line agents: methotrexate, azathioprine
 Intravenous immunoglobulin improves strength
Prognosis
 Most patients with polymyositis and dermatomyositis
respond to treatment, one third return to normal strength
 A few patients are refractory to all forms of therapy
Vasculitis
 Inflammation and necrosis of the blood vessel wall
 Associated may be compromise of the vessel lumen → ischemic
changes in tissues
 Probable result of immunopathogenic mechanism (e.g., deposition of
circulating immune complexes activation of C5a chemotaxis of
neutrophils → release of collagenase and elastase → damage of vessel
wall)
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Seminars for the 5th year
Internal medicine
Prof. Jiří Horák
Clinical spectrum of vasculitis
Polyarteritis nodosa group
 Classic polyarteritis nodosa
 Allergic angiitis and granulomatosis (Churg-Strauss disease)
 Overlap syndrome
Hypersensitivity vasculitis
 Henoch-Schoenlein purpura
 Serum sickness
 Vasculitis associated with infectious diseases
 Vasculitis associated with neoplasms
 Vasculitis associated with connective tissue diseases
 Vasculitis associated with other underlying diseases
Granulomatous vasculitis
 Wegener’s granulomatosis
 Giant cell arteritides
o Temporal arteritis
o Takayasu’s arteritis
Other vasculitic syndromes
 Behcet’s disease
 Thrombangiitis obliterans
 Erythema nodosum
 Erythema multiforme
 Vasculitis isolated to the central nervous system
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