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Rheumatoid arthritis
History
A 34-year-old woman attends the rheumatology outpatient clinic with a 6-month history of painful hands. Previously fit and
well, she developed mild pain in her metacarpophalangeal (MCP) joints which deteriorated over a few weeks to profound pain
and marked stiffness affecting both hands and wrists, particularly in the morning. Her symptoms are now
very intrusive. Her general practitioner has prescribed diclofenac with minimal benefit. She is otherwise well
but is becoming isolated and depressed; she delayed going to see her GP because she was concerned that she
had developed the same ‘rheumatism’ as her grandmother who was wheelchair-dependent.
Examination
This woman is thin and tearful. She has marked soft-tissue swelling of her wrists, MCPs and several proximal
interphalangeal (PIP) joints in both her hands, and has reduced grip strength bilaterally. Apart from a
non-tender nodule on her elbow, the rest of her examination is entirely normal
History
A 46-year-old man with rheumatoid arthritis attends an emergency review at his rheumatology department. His joint disease
is well-controlled on methotrexate 20 mg/week. Over the last few weeks, however, he has become increasingly short of breath
with a marked reduction in exercise tolerance. He has a dry, unproductive cough and, although he denies infective symptoms,
he recalls feeling feverish at the beginning of his illness. He is a non-smoker and there is no relevant occupational history.
Examination
This man is mildly short of breath at rest (18 breaths per minute). He is not febrile. Oxygen saturation is 98 percent on room
air, desaturating rapidly to 88 percent on exercise. Breath sounds are heard throughout both lung fields, with late inspiratory
fine crackles bibasally.
History
A 54-year-old woman is reviewed in the rheumatology clinic. She was diagnosed with seropositive rheumatoid arthritis 14
years ago with prolonged early-morning stiffness, a small-joint arthropathy and a marked acute-phase response (elevated ESR
and C-reactive protein). Despite aggressive therapy with disease-modifying agents, she has never achieved disease remission,
continues to struggle with joint pains and stiffness and struggles with activities of daily living. Her livelihood is at risk as she is
unable to type effectively. She has previously tried methotrexate but it produced marked nausea and deranged
liver function tests at 15 mg/week and had to be stopped. Hydroxychloroquine and azathioprine were both
ineffective. Current medications are leflunomide 20 mg once daily, prednisolone 4 mg once-daily,
alendronate 70 mg weekly and calcichew D3 forte once-daily.
Examination
This woman has marked synovitis with tenderness and swelling of many of her metacarpophalangeal (MCP)
and proximal interphalangeal (PIP) joints, her right wrist and left knee
Chronic inflammatory autoimmune disease involving the synovium of joints
​The usual age of onset is 20 to 40 years; it is more common in women than in men
Family history for RA is not unusual due to the presence of susceptibility genes such as HLA-DR.
Signs and symptoms
1. Morning stiffness lasting >1 hour
2. Joints involved: hands (PIP, MCP) and wrists, knees, ankles, elbows, hips, and shoulders
3. Hand deformities:
a. Ulnar deviation of the MCP joints
b. Boutonnière deformities of the PIP joints
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c. Swan-neck contractures of the fingers
4. Low-grade fever, weight loss and fatigue.
5. Subluxation and instability of cervical spine is common at C1-C2 (a life threatening
complication of RA, radiographs should be performed prior to any surgery to prevent
neurologic damage)
6. Cardiac involvement may include pericarditis, pericardial effusions, conduction
abnormalities, and valvular incompetence
7. Pulmonary involvement; usually pleural effusions; interstitial fibrosis
8. Ocular involvement; episcleritis, anterior uveitis, keratoconjunctivitis sicca or scleritis
with dry eyes.
9. Soft tissue swelling
10. Drying of mucous membranes; Sjögren xerostomia
11. Subcutaneous rheumatoid nodules over extensor surfaces and visceral organs ( the presence of
rheumatoid nodules on examination indicates such seropositivity and a worse prognosis)
12. Nervous system involvement; mononeuritis multiplex
13. Blood: Anemia, Felty syndrome: triad of RA, neutropenia and splenomegaly.
14. Renal system: NSAID-induced nephropathy and Amyloid
15. Patients have an increased tendency to infections.
Pathogenesis:
Environmental triggers at mucosal surfaces→ PADs are induced→ arginine is converted into citrulline→ Modified proteins are
presented to T cells after being processed by APCs; such as dendritic cells→ local and systemic production of antibodies directed
against the altered peptides.
ACPAs and cytokines→ increase in the circulation years before RA symptoms occur→ sudden formation of immune
complexes→ increases vascular permeability in the synovium and activates synovial cells→ inflammatory mediators contribute
to initiation and perpetuation of arthritis→ damage and destruction of cartilage
Diagnosis:
LABs
1. RF is associated with the severity of the disease- nonspecific (RF is found in other inflammatory conditions
(e.g. Sjögren’s syndrome, cryoglobulinemia), certain infections and apparently healthy individuals)
Helpful in determining prognosis. High titers → more severe disease
2. Anti Citrullinated peptide/protein antibodies (ACPA)
3. ↑ ESR, ↑ CRP
4. Anemia of chronic disease
5. ↑ anti CCP (RA associated with ILD)
6. Renal and liver functions
7. Immunoglobulins and protein electrophoresis
RADIOGRAPHS
Not required for a diagnosis of RA
1. Loss of juxta-articular bone mass
2. Narrowing of the joint space
3. Bony erosions at the margins of the joint.
4. Soft-tissue swelling
5. Osteopenia
6. Joint space narrowing
evidence of joint destruction and ankylosis of bones on Xray in some patients.
Synovial fluid analysis can be done to exclude infections or crystalline arthritis.
Disease activity is measured by: disease activity score (DAS), which is a composite score of the clinical evidence of
synovitis, the current inflammatory response and the patient’s own assessment of their health.
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Treatment:
Non pharmacological; the goal is to minimize the swelling, and exercise.
Pharmacological;
1. NSAIDs
2. ↓dose corticosteroids
3. DMARDs (Methotrexate, alternatives: leflunomide, sulfasalazine, hydroxychloroquine, if not effective:
anti-TNF (infliximab), Non-TNF biologics (abatacept, rituximab, tofacitinib))
- LFTs should be performed when prescribing methotrexate to prevent liver toxicity
4. Surgery (Synovectomy, Joint replacement surgery)
Methotrexate side effects: GI upset, oral ulcers, mild alopecia, bone marrow suppression, pulmonary fibrosis.
Methotrexate lung is an idiosyncratic reaction occurs more commonly in the first 2–3 years of treatment
As TNF-a is associated with increased risk of increased malignancy, lymphoma and reactivation of tuberculosis.
Diagnosis for methotrexate lung:
- full blood count, elevated eosinophils, elevated CRP, pulmonary function test and CT of lungs
Treatment of methotrexate lung:
- Oral corticosteroids, with cessation of the drug,
- Progressive form is hard to treat and called Hamman–Rich syndrome
- Steroids and cyclophosphamide
radiological evidence of active inflammation in the form of ground-glass shadowing
Differential diagnosis:
1. Rheumatoid arthritis
2. Psoriatic arthritis in association with skin and typically nail disease
3. Post-infective arthritis (septic)
4. Systemic lupus erythematosus in the presence of pronounced extra-articular symptoms and a positive ANA
5. Parvovirus arthropathy, particularly in those with contact with small children
Complications:
1. Cervical spine Subluxation
2. Nephrotic syndrome due to NSAIDs and amyloids
3. Osteopenia
4. Secondary osteoporosis due to steroid use
Differential diagnosis for a breathless rheumatoid patient
a. Rheumatoid lung: interstitial lung disease, generally a non-specific interstitial pneumonitis
b. Drug reaction causing allergic alveolitis (methotrexate)
c. Coexistent infection: bacterial or pneumocystis pneumonia
d. Pleural effusion
e. Bronchiolitis obliterans
Osteoarthritis
History
An 80-year-old man presents with progressively worsening pain in his left groin and buttock
radiating to the knee with no pins and needles. There is no history of pre-existing trauma or
disease in that hip. He complains of pain made worse on walking and has difficulty in
putting on shoes and tying shoe laces. He obtains only partial relief of the symptoms with
analgesia and rest.
Examination
The patient walks with an antalgic gait. He has a fixed flexion deformity of 10 degrees. His
range of motion in the left hip is restricted and painful in all directions. There is no neurovascular deficit in the leg.
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History
A 73-year-old woman presents with left knee pain. This pain has gradually deteriorated over the last
three years. She reports early-morning stiffness in the knee. Her walking distance has reduced
significantly and is limited due to pain. She obtains minimal relief with analgesia and rest. She has
noticed some swelling in the knee and finds walking over uneven surfaces painful, and she finds going
down stairs difficult. She has developed pain at night that keeps her awake. She has no history of trauma
or infection. She reports no pain in her hips or back.
Examination
This woman has valgus (knock) knees with the left more affected than the right, associated with an
effusion. She has an antalgic gait. She has marked tenderness over the lateral joint line and crepitus in
the patellofemoral joint. She has flexion from 5 to 85 degrees with correctable valgus deformity
degeneration of cartilage with hypertrophy of bone at the articular margins
Any joint can be affected, but weight-bearing joints are most commonly involved (hips, knees, cervical, and lumbar spine)
Usually affects people older than 60 years of age
Modified risk factors
-
Obesity and excessive joint loading
Occupation
Smoking
Bone density
Physical activity
Deposition diseases
Hemophilia
Non modified risk factor
-
Age
Gender
Genetic
Joint injury (repeated microtrauma or macrotrauma)
Altered joint anatomy
Signs and symptoms:
1. Joint pain (often monoarticular)
a. This is caused by movement of one joint surface against another
due to cartilage loss
b. Deep, dull progressive ache that is relieved with rest and worsened
with activity
2. Morning stiffness for less than 30 minutes
3. Limited range of motion due to bony enlargement of joints
4. Crepitus may be present
5. Absence of erythema or warmth over the involved joints
6. Swelling indicates inflammation
7. Heberden and Bouchard nodes on fingers
8. If the spine is involved, nerve roots may become compressed and lead to radicular pain.
Pathogenesis:
Injury or damage to the cartilage→ pro inflammatory factor→ produce proteolytic enzymes→ responsible for the degradation
and damage to the matrix→ chondrocytes multiply and form clusters→ bony lumps form called bone spurs.
Damage to the matrix→ also causes thickening of the bone underneath the cartilage→ fluid-filled areas in the bone called bone
cysts→ +inflammation of the joint’s synovium.
Age-related matrix change → abnormal calcification referred to as chondrocalcinosis → from accumulation of calcium
pyrophosphate dihydrate CPPD crystal- aka pseudogout
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Diagnosis:
LABS
1. Blood tests are normal
RADIOGRAPHS
1. Plain radiographs:
a. Joint space narrowing due to loss of cartilage
b. Osteophytes; bony spurs
c. Sclerosis of subchondral bony end plates adjacent to diseased cartilage
d. Subchondral cysts on acetabular and femoral sides
2. MRI of the spine if indicated (neurologic findings, before surgery)
Clinical signs on examination may include an antalgic gait, positive Trendelenburg sign, unequal leg length, muscle wasting, and
a restriction of hip joint movements.
Treatment:
Nonpharmacologic treatment.
1. Avoid activities that involve excessive use of the joint.
2. Weight loss.
3. Physical therapy can be beneficial, mainly anaerobic.
4. Use canes or crutches to reduce weight on the joint.
Pharmacologic treatment.
1. Acetaminophen
2. NSAIDs (GI bleeding is a concern with long-term use)
3. COX-2 inhibitors
4. Intra-articular injections of corticosteroids, 3-4 injections per year
5. Viscosupplementation; hyaluronic acid is injected into the knee joint
Surgery for a serious disability.
Nutritional products; glucosamine and chondroitin sulfate.
Secondary causes of osteoarthritis:
a. developmental dysplasia of the hip
b. septic arthritis of the hip
c. Perthes’ disease
d. slipped capital femoral epiphysis
e. rheumatoid arthritis
f. seronegative arthropathy
g. trauma
h. crystal arthropathy
i. avascular necrosis of the femoral head
Osteoporosis
History A 58-year-old woman presents to the emergency department with acute back pain. She stumbled off a step and,
although she denies falling or receiving direct trauma to the spine, she developed acute and severe mid-thoracic pain
immediately afterwards. Her past medical history is unremarkable. She admits to drinking up to 30 units of alcohol a week
and smokes 30 cigarettes per day. Examination This woman is thin and in considerable pain. The pain is central with no
radiation. There are no peripheral stigmata of systemic disease and cardiovascular, respiratory, abdominal and neurological
examinations are normal. She has a marked kyphosis and has point tenderness over several thoracic vertebrae.
Decreased bone mass/quality causes increased bone fragility and fracture risk
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It is often difficult to differentiate between primary and secondary osteoporosis, and the two may coexist. It is best to attempt to
identify any predisposing conditions and eliminate them if possible.
Most patients are postmenopausal women due to decreased estrogen and elderly men
Osteoporosis is a “silent” disease. It is asymptomatic until a fracture occurs
An exercise program along with calcium and vitamin D supplementation is the mainstay of the therapy for prevention or
treatment of osteoporosis.
When taking history, ask the patient about hemoptysis and recent weight loss.
1.
maternal family history of hip fracture
2.
oestrogen deficiency (e.g. premature menopause, prolonged secondary amenorrhoea)
3.
corticosteroid therapy with a prednisolone dose >7.5 mg/day for over 6 months
4.
low BMI (<19 kg/m2), due to a combination of reduced estrogen levels and reduction in impact loading
5.
smoking and excess alcohol
6.
anorexia nervosa
7.
prolonged immobilization.
Bone mass or mineral density relies on a balance of osteoblastic and osteoclastic activity.
Postmenopausal bone loss is the most common cause of osteoporosis, but secondary osteoporosis may occur in the context of a
number of medical conditions: • postmenopausal oestrogen deficiency (most common cause) • amenorrhoea • iatrogenic
(corticosteroid therapy) • endocrine (hyperparathyroidism, hyperthyroidism, Cushing’s disease, hypopituitarism,
hypogonadism) • malabsorption (e.g. coeliac disease) • osteomalacia • multiple myeloma • inflammatory arthropathy (probably
due to elevated IL-1 and/or TNF-a).
Classification:
1. Primary osteoporosis (two types that are impractical clinically)
a. Type I (most often in postmenopausal women 51 to 75 years of age), excess loss of trabecular bone;
vertebral compression fractures and Colles fractures (a distal radius fracture) are common
b. Type II (most often in men and women over 70 years of age), equal loss of both cortical and trabecular
bone; fractures of femoral neck, proximal humerus, and pelvis most common
2. Secondary osteoporosis is when an obvious cause is present, such as excess steroid therapy/ Cushing syndrome,
immobilization, hyperthyroidism, long-term heparin, hypogonadism in men, and vitamin D deficiency
Risk factors:
Modifiable risk factors
-
-
Estrogen depletion (modified by giving HRT)
a. Postmenopausal state, all women are
estrogen deficient after
menopause;however, osteoporosis does not
develop in all women
b. History of athletic amenorrhea, eating
disorders, oligomenorrhea
c. Early menopause
Calcium deficiency/vitamin D deficiency
Decreased physical activity or prolonged immobility
Endocrine, hypogonadism in men (with low
testosterone), hyperthyroidism
Smoking and alcohol abuse
Medications, corticosteroids, prolonged heparin use
Non- modifiable risk factors
-
Female gender, women have a lower peak bone mass
and smaller vertebral end plates (non modified)
Decreased peak bone mass
Heritable risk factors, family history, European or
Asian ancestry, thin/slight build
Signs and symptoms:
1. Vertebral body compression fractures ( middle and lower thoracic and upper lumbar spine) are the most
common. Very rare in cervical spine
a. Result in pain and deformity, including kyphosis
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b. Severe back pain after minor trauma
c. Restricted spinal movement, loss of height
2. Colles fracture (distal radius fracture) are usually due to fall on outstretched hand; more common in
postmenopausal women
3. Hip fractures; femoral neck, intertrochanteric fractures
4. Increased incidence of long bone fractures (humerus, femur, tibia)
Pathogenesis:
consequence of genetic, hormonal, dietary, lifestyle and physical factors→ failure to attain optimal (peak) bone mass before age
30, or rate of bone resorption exceeds rate of bone formation after peak bone mass is attained→ decreased bone density→
increased susceptibility to fractures and osteoporosis
Diagnosis:
1. DEXA (dual-energy x-ray absorptiometry) scan is the gold standard.
a. Indications for bone mineral density measurement:
i.
All women 65 and older
ii.
Postmenopausal women <65 with one or more risk factors for fracture.
iii.
Men with risk factors for fracture.
b. Sites are femoral neck and lumbar spine. Must be compared with the bone density of a healthy
30-year-old
c. T-scores are used and can range from normal to osteopenia to osteoporosis.according
2. Rule out secondary causes—check calcium, phosphorus, alkaline phosphatase, TSH, vitamin D, free PTH,
creatinine, CBC.
3. X-Ray may show wedge fractures of the involved bones
Treatment:
- Nonpharmacologic therapy
1. Diet—adequate calorie intake, avoid malnutrition
2. Supplemental elemental calcium and vitamin D
3. Exercise; weight-bearing exercise for 30 minutes, at least 3 times a week, to stimulate bone formation
4. Smoking cessation is critical—smoking accelerates bone loss
5. Eliminate or reduce alcohol intake
6. Hormone replacement therapy is used to prevent osteoporosis but has no beneficial effect in already presented
diseases.
- Pharmacologic therapy
Indicated in the following patients:
- Postmenopausal women with established osteoporosis or fragility fracture (hip or vertebral)
- High-risk postmenopausal women with osteopenia
1. Bisphosphonates inhibit bone resorption and are first-line treatment
a. They decrease osteoclastic activity and decrease the risk of fractures
b. Oral bisphosphonates (alendronate, risedronate) are preferred in most patients
c. Side effects include reflux, esophageal irritation, and ulceration
d. If patient cannot tolerate oral bisphosphonates, use IV bisphosphonates (IV zoledronic acid)
2. PTH therapy or human recombinant PTH therapy
- PTH is an effective drug that increases bone mineral density and reduces fracture risk.
- Not first line therapy due to its cost
- Indicated in patients with severe osteoporosis who cannot tolerate bisphosphonates, or who continue
to fracture despite being on bisphosphonates for 1 year
- Maximum duration of treatment is 24 months, because of concern for osteosarcomas, which have
been observed in rats.
- After stopping PTH, can restart bisphosphonates
3. Calcitonin (can be administered by nasal spray), only useful as short-term therapy
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4. Estrogen–progestin therapy is no longer a first-line treatment in postmenopausal women because of increased
risk of breast cancer, stroke, venous thromboembolism, and perhaps CAD
Systemic Lupus Erythematosus
History
A 27-year-old Afro-Caribbean woman presents to the rheumatology clinic with a long history of painful hands and oral
ulcers. She feels she ‘hasn’t been well’ for many years with various problems including chest pains, occasional rashes and hair
loss. She recently visited her family in Jamaica and felt much worse, with a resurgence of all of her symptoms, particularly the
rash. She is currently experiencing an attack of her typical central chest pain which is sharp and relieved by sitting forward.
Examination
This young woman is uncomfortable and slightly short of breath. Pulse is 115/min sinus rhythm, blood pressure 95/62
mmHg, and oxygen saturation 98 percent on room air. Her jugular venous pressure (JVP) is elevated at 2 cm and her heart
sounds are quiet with no added sounds. Chest examination reveals stony dull bases with reduced vocal resonance
and diminished breath sounds.
History
A 28-year-old woman presents with a 3-day history of a facial rash and swelling of her ankles. She has never had a rash before,
has not changed her facial cream or been exposed to anything that might precipitate an allergic reaction. The swelling of the
ankles coincided with the development of the rash. Initially it was mild with ‘sock-marks’ around her ankles, but now the
swelling is more pronounced and has spread up to her knees. She is otherwise well and on no medication.
Examination
This young woman has a maculopapular rash across the bridge of her nose and cheeks with sparing of the nasolabial folds.
There is pitting oedema of the lower limbs to just above the knee. She is hypertensive at 154/90 mmHg, but the remainder of
the examination is normal.
History
A 38-year-old patient presents to the emergency department with acute pleuritic chest pain and breathlessness. She denies
cough, infective symptoms or risk factors for deep venous thrombosis. She is otherwise well. Her medical history includes
lupus erythematosus which is currently in remission, and a second-trimester miscarriage.
Examination
This woman is uncomfortable and short of breath at rest with a respiratory rate of 16 breaths per
minute. Her pulse is 96/min sinus rhythm, blood pressure 115/68 mmHg, and oxygen saturation 90
percent on room air. She is not febrile. The remainder of her clinical examination is normal.
→ likely diagnosis for the current presentation is pulmonary embolism diagnosed by history of
sudden-onset pleuritic chest pain and shortness of breath.
The diagnosis is Antiphospholipid syndrome
History
A 22-year-old woman consults her general practitioner complaining of fever, joint pains and chest pain. The joint pains began
3 weeks previously and affected the small joints of her hands and wrists with moderate early-morning stiffness. The muscle
pains are relatively non-specific and are not associated with any loss of power. Overall she has derived some benefit from
treatment with regular non-steroidal anti-inflammatory drugs (NSAIDs). In the last 48 hours, however, she has also
developed a low-grade fever and a sharp right sided chest pain on deep inspiration. She denies breathlessness or cough and has
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no risk factors for pulmonary embolism. Her medical history includes acne, for which she has been taking minocycline for the
past year.
Examination
This young woman is well, with a normal respiratory rate and oxygen saturations. Her temperature is 37.6°C. Although her
joints are tender she has no objective evidence of synovitis. Respiratory examination reveals a pleural rub over the painful area
in the right lower zone anteriorly but is otherwise normal. The GP was concerned she had developed systemic lupus
erythematosus (SLE) and ordered some basic blood tests and an immunology screen.
autoimmune disorder leading to inflammation and tissue damage in multiple organ systems.
SLE is an idiopathic chronic inflammatory disease with genetic, environmental, and hormonal factors (estrogen).
It is less common in children and usually occurs in females of reproductive years. African-American patients are more frequently
affected than Caucasian patients
a multisystem autoimmune condition characterized by antibodies directed against nuclear components.
Types of SLE
I.
Spontaneous SLE
II.
Cutaneous lupus erythematosus (skin lesions without systemic disease)
III.
Drug-induced lupus (procainamide, isoniazid, phenytoin, hydralazine, quinine)
IV.
ANA-negative lupus—associated findings; 1. Arthritis, 2. Raynaud phenomenon, 3. subacute cutaneous lupus
Environmental factors of SLE
➔ Ultraviolet light (UV- A, B)
➔ Hormones, e.g. oestrogens, prolactin
➔ Viral infections, e.g. EBV, CMV, retroviruses, parvovirus B19
➔ Chemicals and heavy metals, e.g. silica and mercury
➔ Drugs, e.g. hydralazine, procainamide, isoniazid, quinidine, methyldopa, chlorpromazine, minocycline
Minocycline induces anti-histone antibodies only in up to 15 per cent of cases, and up to three-quarters of patients generate a
positive pANCA; drug should be stopped
Signs and symptoms:
1. Constitutional symptoms: Fatigue, malaise, fever, weight loss.
2. Cutaneous: Butterfly or malar rash, photosensitivity, discoid lesions, oral or nasopharyngeal ulcers
(mucosal involvement), alopecia, raynaud phenomenon.
3. Musculoskeletal: Arthralgias, arthritis (2 or more joints), myalgia.
4. Cardiac: Pericarditis, endocarditis (Libman–Sacks endocarditis), myocarditis
5. Pulmonary: Pleuritis (serosal involvement), pleural effusion, pneumonitis, pulmonary HTN.
6. Hematologic: Hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia.
7. Renal: Proteinuria >0.5 g/day, glomerulonephritis, azotemia, pyuria, uremia, HTN.
8. Immunologic: Impaired immune response due to many factors, including autoantibodies to lymphocytes,
abnormal T-cell function, and immunosuppressive medications; often associated with antiphospholipid
syndrome
9. GI: Nausea and vomiting, dyspepsia, dysphagia, peptic ulcer disease
10. CNS: Seizures, psychosis, depression, headaches, TIA, cerebrovascular accident
11. Ocular manifestation; sicca syndrome (sjogren's syndrome), nonspecific conjunctivitis, retinal vasculitis, optic
neuritis, cataract, and glaucoma.
Pathogenesis:
Systemic lupus erythematosus→ global loss of self-tolerance with activation of autoreactive T and B cells→ production of
pathogenic autoantibodies and tissue injury→ activation of innate immune cells via Fc receptor (FcR)-mediated uptake of
complexes→ tissue destruction and vasculitis→ production of symptoms
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Cytokines in patients with SLE
IL-2
IL-6
IL-10
IL-12
Other cytokines
↑Serum IL-15, IL-16, and IL-18 concentrations
↑IFN-γ mRNA expression in PBMCs
↑Serum IFN-γ
Diagnosis:
1. First step in diagnosis must be checking the presence of inflammation by ESR, CRP, C3 and C4 in immune
complexes
2. CBC, hemoglobin level…
3. The patient must have at least 4 criteria out of 11, or biopsy proven lupus nephritis with a positive ANA or
anti-dsDNA.
4. Autoantibodies in lupus:
a. ANA: Sensitive but not specific.
b. Anti-ds DNA: very specific but not sensitive- during active disease.
c. Anti-Smith: very specific but not sensitive.
d. Antiphospholipid antibody positivity: as determined by 1. positive lupus anticoagulant (less specific), 2.
high-titer anticardiolipin antibody level (gives false positive for syphilis), or 3. positive anti-β-2 glycoprotein.
e. Antihistone Abs: are present in most cases of drug-induced lupus. If negative, drug-induced lupus can be
excluded.
f. Ro (SS-A) and La (SS-B) are found in. Associated with:
➔ Sjögren syndrome
➔ Subacute cutaneous SLE
➔ Neonatal lupus (with congenital heart block)
➔ Complement deficiency (C2 and C4)
➔ ANA-negative lupus
5. LABS and RADIOGRAPHS
➔ CBC shows anemia, leukopenia, lymphopenia or thrombocytopenia
➔ ↑ESR and CRP
➔ Urinalysis; in cases of lupus nephritis
➔ X-Rays
6. In cases of lupus nephritis; biopsy is indicated
Antiphospholipid syndrome- APPS:
➔ Hypercoagulable state
➔ More prone to clots
➔ Deep vein thrombosis
➔ Hepatic vein thrombosis
➔ Stroke
Lifelong anticoagulation therapy for APPS
Diagnosis of PE associated with APPS: chest X-ray, CT–pulmonary angiogram, ECG to exclude complications
- History of lupus, miscarriages, and thromcocytopenia are diagnostic
- lupus anticoagulant or anticardiolipin antibody
Extra clinical features: cardiac valvular disease, livedo reticularis, mild chronic thrombocytopenia, neurological disease such as
chorea or transverse myelitis
Antiphospholipid syndrome may occur independently of SLE.
Estrogen containing contraceptive and HRT are contraindicated in women with APPS
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Treatment:
1.
2.
3.
4.
Avoid sun exposure because it can exacerbate cutaneous rashes
NSAIDs; for less severe symptoms
Either local or systemic corticosteroids; for acute exacerbations
Systemic steroids for severe manifestations (Methotrexate and azathioprine)
- Methotrexate side effects: GI upset, oral ulcers, mild alopecia, bone marrow suppression, pulmonary
fibrosis.
5. Antimalarial agents such as hydroxychloroquine; best long-term treatment, associated with production of
retinal toxicity.
6. Cytotoxic agents such as cyclophosphamide or mycophenolate mofetil; for systemic diseases and active
glomerulonephritis
7. ACE Inhibitors to treat and control HTN if present with lupus nephritis
8. Diuretics to treat edema associated with lupus nephritis
9. Monitor the following and treat appropriately:
a. Renal disease, which produces the most significant morbidity
b. HTN
c. Retinal toxicity
Cyclophosphamide reduces fertility and this side-effect should be specifically discussed with patients of child-bearing age;
mycophenolate mofetil is preferred.
Periods of flare ups * prevention of flare ups is by avoiding sunlight
⤷
⤴ *corticosteroids and immunosuppressants are used to limit severity
Remission
Conditions in Which ANAs Are Elevated
1. SLE
2. RA
3. Scleroderma
4. Sjögren syndrome
5. Mixed connective tissue disease
6. Polymyositis and dermatomyositis
7. Drug-induced lupus
Associated conditions:
1. antiphospholipid syndrome
2. lupus nephritis
- anti-DNA immune complexes deposition in glomeruli
- nephritic or nephrotic syndrome
- diffuse proliferative is the most common and most severe type
3. drug-induced lupus
- typically positive for antinuclear and antihistone antibodies
- typically without renal or neurologic involvement
4. Libman-Sacks endocarditis (LSE)
- noninfectious endocarditis characterized by thrombi on the mitral or aortic valves (LSE in SLE)
5. Raynaud phenomenon
6. neonatal lupus erythematosus
- associated with patients with anti-Ro or anti-La antibodies
- neonates present with rashes and congenital heart block
Complication:
- Renal disease remains the most feared complication of lupus and all patients (including this one!) should have
their blood pressure checked, urine examined for casts and serum creatinine checked regularly.
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Scleroderma
History
A 36-year-old woman is referred by her general practitioner with cold, painful hands and shortness of breath on exertion. Over
the last 6 weeks she has noticed her fingers and hands turning blue, then white and finally red and painful in episodic attacks,
particularly in the cold. In addition the skin on her fingers feels taut, reducing her ability to make a fist. The shortness of
breath and reduced exercise tolerance has developed insidiously over the same period but she has not had a cough or infective
symptoms. She has no history of, or risk factors for, respiratory disease.
Examination
This woman is dyspnoeic on walking from the waiting room to the clinic; her oxygen saturations are initially 92 percent but
increase to 99 percent with rest. She has no peripheral stigmata of respiratory disease. The skin over her fingers and hands is
tight and bound-down but is intact with no evidence of ulcers or vasculitis. The thickened skin extends beyond her elbows
and she also has restricted mouth opening. Her jugular venous pulse is elevated, with a parasternal heave and a loud second
heart sound, but there is no peripheral oedema. In the respiratory system she has bibasal mid-to-late fine inspiratory crackles
A chronic connective tissue disorder that can lead to widespread fibrosis.
Skin is tight and shiny, with no wrinkles or folds.
May lead to cancer in some cases.
Scleroderma is more common in women. Average age of onset is 35 to 50 years.
There are two types of scleroderma: Diffuse (20%) and limited (80%)
Only diffuse scleroderma form has renal, lung, and heart involvement
Signs and symptoms:
1. Constitutional symptoms: discomfort, fatigue, weight loss
2. Raynaud phenomenon
a. Present in almost all patients; usually appears before
other findings
b. Caused by vasospasm and thickening of vessel walls in the digits
c. Can lead to digital ischemia, with ulceration and infarction/gangrene
d. Cold temperature and stress bring about color changes of fingers; blanching first, then cyanotic, and
then red from reactive hyperemia
3. Cutaneous fibrosis- CREST syndrome
a. Tightening of skin of the face and extremities
(sclerodactyly refers to a clawlike appearance of the hand,
and reduces the function of the hand)
b. Can lead to contractures, disability, and disfigurement
c. “puffy fingers” from interstitial non-pitting oedema
d. Mucocutaneous telangiectasia: dilation of superficial
capillaries mostly on face or oral mucosa
e. Skin ulcerations due to breakdown of atrophic skin
4. GI involvement
a. Occurs in most patients (both diffuse and limited)
b. Findings include dysphagia/reflux from esophageal immobility (due to connective tissue disorder),
delayed gastric emptying, constipation/diarrhea, abdominal distention, and pseudo-obstruction.
Prolonged acid reflux may eventually lead to esophageal strictures
c. GERD due to decreased motility in the lower ⅔ of the esophagus
5. Pulmonary involvement
a. Most common cause of death from scleroderma
b. Interstitial fibrosis and/or pulmonary HTN due to connective tissue disorder, affecting the vessels
Muran Mjahed 13
-
ILD has a restrictive pattern: FEV1 /FVC ratio is normal or increased. All lung volumes are
low. Both FEV1 and FVC are reduced, but the ratio is often preserved
c. On radiographs: honeycomb appearance or ground glass opacities in the lower lobes of the lung
6. Cardiac involvement
a. pericardial effusions
b. myocardial involvement that can lead to CHF ( in the case above; right
sided heart failure), arrhythmias
c. HTN and CAD
7. Renal involvement
a. renal crisis; rapid malignant hypertension, occurs in patients with diffuse
disease
b. Glomerulonephritis with sclerotic kidneys
c. Renal failure
limited long standing SS associated with raynaud’s phenomenon → acro-osteolysis
Patterns of limited disease occur as isolated fibrotic plaques (morphoea) or bands of affected skin (linear scleroderma, also known
as ‘en coup de sabre’ when found on the face).
Pathogenesis:
Endothelial injury → intimal proliferation → vasoconstriction → hypoxia; ↑ROS, ↑PAH → angiogenesis → platelet aggregation
→ fibrosis and innate humoral immunity (macrophages, mast cells, cytokines…)
3 fundamental aspects of Systemic Sclerosis;
1. ↑ inflammation
2. ↑ vasoconstriction, and angiogenesis
3. ↑ fibroproliferation of vessel wall
After endothelial cell dysfunction: ↑ET-1, ↑platelets, ↑adhesion molecules, ↑ IL33, ↓NO
Diagnostic tests:
1. Almost all patients have elevated ANAs, (high sensitivity, low specificity).
2. Anticentromere antibodies are very specific for the limited form.
3. Anti-RNA polymerases
4. Anti Topoisomerase I Ab ( antiscleroderma-70 or anti-SCL 70 indicated severe disease) is very specific for the
diffuse form.
5. Barium swallow (esophageal dysmotility) and pulmonary function tests are used to detect complications.
6. Nailfold capillaroscopy
7. Labs:
a. CBC; anemia from malabsorption, iron deficiencyI or from bleeding in the GI.
b. Serum creatinine; level indicates renal dysfunction
c. CK; elevated in patients with myopathy or myositis
d. Urinalysis with urine sediment; proteinuria and/or cellular casts
e. Modified Rodnan Skin Score (mRSS); used to measure thickness of skin, pliability, and fixation to
underlying structures.
f. Durometer, Plicometer, High frequency Ultrasound
Treatment:
1. No effective cure, and treatment is symptomatic depending on the organs involved
2. NSAIDs for musculoskeletal pains
3. H2 blockers or proton pump inhibitors for esophageal reflux, plus pro motility (metoclopramide)
4. Raynaud phenomenon; avoid cold and smoking, keep hands warm; if severe, use calcium-channel blockers;
nifedipine
5. ACE inhibitors are used to prevent and treat renal hypertensive crisis
6. Diuretics for heart failure
7. For severe diffuse skin and organ involvement, systemic immunosuppression is indicated
8. Antibiotics for skin infection
Muran Mjahed 14
Sjogren Syndrome
History
A 79-year-old man presents to his general practitioner with bilaterally swollen cheeks. He also complains of feeling ‘tired all
the time’, weight loss and occasional night sweats. Although he admits to an irritating dry cough he denies frank
breathlessness or change in exercise tolerance. His medical history includes hypertension, for which he takes ramipril.
Examination
This elderly man is slightly pale, with bilateral parotid enlargement and cervical
History
A 44-year-old woman presents to the rheumatology department with a long history of sore, stiff hands and dry, painful eyes.
She delayed seeking medical attention as she was concerned she had developed rheumatoid arthritis. The pain in her hands
affects principally her wrists, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints with protracted
early-morning stiffness. Her eyes feel ‘gritty’ much of the time, getting worse as the day progresses such that they are very
painful by the end of the day. During her worst symptoms she complains of photophobia. She has recently noticed a
reduction in saliva and finds it difficult to eat dry foods without ‘washing them down with water’. Her medical history is
unremarkable and she is on no regular medication.
Examination
This woman is well with mild synovitis of her wrist, MCPs and PIPs. Her sclerae are minimally injected but there is no
discharge and her acuity is normal. The remainder of her examination is normal.
Sjögren syndrome is an autoimmune disease most common in women.
Lymphocytes infiltrate and destroy the lacrimal and salivary glands
A multiorgan disease (can also involve the skin, lungs, thyroid, vessels, and liver)
Parotid enlargement differentials: Sjögren’s syndrome, sarcoidosis, lymphoma
Sjögren’s syndrome is often associated with a polyclonal hypergammaglobulinemia and may develop lymphoma
Types:
Primary Sjögren syndrome: Dry eyes and dry mouth, along Secondary Sjögren syndrome: Dry eyes and dry mouth
with lymphocytic infiltration of the minor salivary glands (on along with a connective tissue disease (RA, systemic sclerosis,
histology)
SLE, polymyositis)
patients do not have another rheumatologic disease
Signs and symptoms:
1. Dry eyes, burning, redness, blurred vision, keratoconjunctivitis sicca
2. Persistent dry mouth (Xerostomia) and tooth decay; with difficulty
swallowing dry food, inability to speak continuously
3. Arthralgias, arthritis, fatigue, peripheral joint pain
4. Interstitial nephritis and vasculitis
5. Swelling of parotid and submandibular glands
6. Urticaria of limbs
7. Pulmonary involvement in some patients; chronic cough, dyspnoea, upper
and lower respiratory infections. Radiographs show ground-glass pattern, thickened
bronchial walls
8. Renal involvement characterized by interstitial renal disease, and glomerulonephritis
9. ⅓ of patients with primary SjS have thyroid disease.
Muran Mjahed 15
10. Patients have increased risk of non-Hodgkin lymphoma. Malignancy is the most common cause of death
Ask patients with sjogren if swallowing biscuits and bread is hard without water
Pathogenesis:
lymphocytic infiltrates → destruction of the salivary and lacrimal glands → systemic production of autoantibodies to the
ribonucleoprotein particles Ro (SS-A) and La (SS-B) →The infiltrating cells; T- and B-cells, dendritic cells interfere with
glandular function → resulting in dry eyes and dry mouth due to decreased secretions from the salivary glands.
Diagnosis:
1. ANAs are present in most patients. Rheumatoid factor (RF) is also present in many patients with secondary
disease.
2. Ro (SS-A) is present in 60% of patients, and La (SS-B) (which is more specific) is present in 40% of patients.
- Patients with antibodies to Ro (SS-A) are at increased risk of having a child with neonatal SLE (with
congenital heart block).
3. Schirmer test: Filter paper inserted in the eye to measure lacrimal gland output (degree of wetting in a specified
time period) has high sensitivity and specificity.
4. Salivary gland biopsy (lip or parotid) is usually not performed, lymphocytic infiltrates.
5. Elevated ESR, CRP normal
6. Ultrasound / CT/ MRI of salivary glands in some cases
7. Biopsy of the salivary glands in severe cases
anti-Ro and anti-La antibodies cross the placenta and cross-react with the developing conducting system in the fetal heart. As a
result, patients of child-bearing age with Ro and La antibodies should be counseled regarding potential fetal heart-block
Treatment:
1. Pilocarpine or Cevimeline (to enhance oral and ocular secretions)
2. Artificial tears for dry eyes
3. Good oral hygiene
4. NSAIDs, steroids for arthralgias, arthritis
5. Patients with secondary Sjögren syndrome must treat any connective tissue disorder
Gout
History A 56-year-old man presents to the emergency department with a 2-day history of an acutely painful, swollen and hot
knee. He is otherwise well but felt feverish on the morning of his admission. There is no history of trauma and the system's
inquiry is unremarkable. Past medical history includes left ventricular failure, hypertension and renal impairment. Current
medications are aspirin, furosemide and ramipril. He lives alone, smoked 15 cigarettes per day and drinks 30 units of alcohol
per week. Examination This man is uncomfortable but well. His temperature is 37.1°C, pulse 110/min and blood pressure
145/83 mmHg. General examination is unremarkable, but his right knee is warm with a tense effusion. Both passive and
active movement are restricted by pain, and weight-bearing is uncomfortable. Other joints are normal
Gout is an inflammatory monoarticular arthritis caused by the crystallization of monosodium urate in joints Hyperuricemia is a
hallmark of the disease, but it is not specific to gout.
Ninety percent of patients are men over 30 years of age.
Women are not affected until after menopause due to decreased
estrogen-mediated urinary urate excretion
Risk factors:
1.
Male >30
2.
Females of postmenopausal years
3.
Obesity
4.
Genetic polymorphism
5.
Kidney diseases
6.
NSAID use
Muran Mjahed 16
7.
Purine rich foods
8.
Alcohol intake
9.
Thiazide and loop diuretics
Risk factors for gout are under-excretion or overproduction of urate, which is a product of DNA breakdown and present in
large amounts in certain foods and alcohol
Signs and symptoms:
1. Intermittent acute monoarthritis especially the first metatarsophalangeal joint (MTP)
2. Desquamation of skin may occur
3. Erythema, pain, swelling, tenderness, and warmth
4. Osteopenia is characteristically absent.
Stages of gout:
1. Asymptomatic hyperuricemia.
a. Increased serum uric acid level in the absence of clinical findings of gout, may be present without
symptoms for 10 to 20 years or longer.
b. Should not be treated
2. Acute gouty arthritis.
a. Initial attack usually involves sudden onset of exquisite pain.
b. Pain often wakes the patient from sleep.
c. Mostly affecting the big toe; the first metatarsophalangeal joint (podagra).
d. Fever may be present.
e. the patient may have desquamation of overlying skin when the attack is gone.
3. Intercritical gout.
a. An asymptomatic period after the initial attack.
b. Between two acute attacks
c. Sixty percent of patients have a recurrence within 1 year.
d. Few patients never have another attack of gout.
e. Attacks tend to become polyarticular with increased severity over time.
4. Chronic tophaceous gout.
a. Occurs in people who have had chronic poorly controlled gout
b. Tophi:
- Aggregations of urate crystals surrounded by giant cells in an inflammatory reaction.
- Tophi causes deformity and destruction of hard and soft tissues and may be extra-articular.
c. Usually on the extensor surface of forearms, elbows, knees, Achilles tendons, and pinna of the external
ear.
Pathogenesis:
Increased production of uric acid (by: 1. Hypoxanthine-guanine phosphoribosyltransferase deficiency 2. Phosphoribosyl
pyrophosphate synthetase overactivity 3. Increased cell turnover)
OR
Decreased excretion of uric acid (by: 1. Renal disease 2. NSAIDs 3. loop and thiazide diuretics 4. Acidosis)
Accumulation of uric acid crystals in the synovial fluid→ PMNs initiate acute inflammation of gout→ IgGs coat monosodium
urate crystals→ leading to the release of inflammatory mediators and proteolytic enzymes from the PMNs→ results in
inflammation
Crystal arthropathy is caused by either uric acid (gout) or pyrophosphate (pseudogout) crystals precipitating out into the
synovial fluid, generating a brisk inflammatory response.
Diagnosis:
1. Arthrocentesis to aspirate joint and analyze synovial fluid under polarized light microscopy; needle-shaped and
negatively birefringent monosodium urate crystals.
positively birefringent brick-shaped crystals in pyrophosphate disease
2. Serum uric acid is not helpful in diagnosis because it can be normal even during an acute gouty attack.
Muran Mjahed 17
3. Blood test; during acute flares, uric acid is decreased in Blood
4. Radiographs:
a. X Ray reveals punched-out erosions and sclerotic margins
b. Ultrasound; double contour or margins of the affected joint
c. CT Scan usually not performed
Complications of Gout:
1. Nephrolithiasis
2. Degenerative arthritis
Urate crystals may also deposit in the skin, causing painful discrete lumps known as tophi, or in the renal tract, causing urate
nephropathy or lithiasis
Treatment:
1. In all stages, avoid secondary causes of hyperuricemia.
- Medications that increase uric acid levels (thiazide and loop diuretics)
- Obesity
- Reduce alcohol intake.
a. Reduce dietary purine intake. Limit intake of seafood/red meat.
2. Acute gout.
a. Bed rest is important.
b. NSAIDs; indomethacin
c. Avoid aspirin (aggravates the symptoms) and acetaminophen
d. Colchicine
i.
An alternative for patients who cannot take or did not respond to NSAIDs.
e. Corticosteroids
i.
Oral prednisone (7- to 10-day course) if patient does not respond to or cannot tolerate
NSAIDs and colchicine.
ii.
Intra-articular corticosteroid injections (if only one joint is involved)
3. Prophylactic therapy.
- at least two acute gouty attacks before initiating prophylactic therapy.
- The presence of tophi is also an indication for prophylactic therapy.
a. When giving prophylaxis, add either colchicine or an NSAID for 3 to 6 months to prevent an
acute attack.
b. Use of uricosuric drugs or allopurinol depends on how much uric acid is excreted in the urine
in a 24-hour period.
- Uricosuric drugs (probenecid, sulfinpyrazone) increase the renal excretion of uric acid, indicated when the 24-h
urine uric acid is <800 mg/day, (underexcretion of urate from kidneys).
- They are contraindicated if the patient has a history of renal stones.
- Xanthine oxidase inhibitors (allopurinol, febuxostat) decrease uric acid synthesis and are indicated when the
24-h urine uric acid is >800 mg/day, (indicates overproduction.)
- They are not contraindicated in kidney dysfunction.
- Uricases (pegloticase, rasburicase) catalyze the conversion of urate into allantoin, a more soluble purine
degradation product. They may cause infusion reactions.
Differential diagnosis may include:
1. Septic arthritis
2. crystal arthritis
- Gout
- Pseudogout
3. Kidney impairment
Muran Mjahed 18
Pseudogout (Calcium Pyrophosphate Deposition Disease)
Calcium pyrophosphate crystals deposit in joints, leading to inflammation.
a form of arthritis characterized by sudden, painful swelling in one or more of the
joints
Risk factors:
1. Deposition increases with age and with OA of the joints.
2. conditions that may increase crystal deposition include
hemochromatosis, hyperparathyroidism, hypothyroidism, and
Bartter syndrome (genetic defect in kidney function).
Signs and symptoms:
1. Symptoms similar to gout but typically occur in larger joints
- The most common joints affected are knees and wrists.
2. It is classically monoarticular, but can be polyarticular.
Pathogenesis:
abnormal formation and deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the cartilage and the synovial
fluid→ leading to a sudden attack of arthritis similar to gout.
Diagnosis:
1. Joint aspirate is required for definitive diagnosis; positively birefringent, rod-shaped and rhomboidal crystals in
synovial fluid (calcium pyrophosphate crystals)
2. Radiographs—chondrocalcinosis (cartilage calcification)
Treatment:
1. Treat the underlying disorder (if identified)
2. Symptomatic management is similar to that for gout
- First-line therapy includes NSAIDs
- Colchicine for prophylaxis
- Intra-articular steroid injections, with triamcinolone
3. Total joint replacement
Polymyalgia rheumatica
History
A 72-year-old woman presents to her general practitioner with a few weeks’ history of pain and stiffness affecting her
shoulders and hips. The pain began insidiously but is now severe; her shoulders and neck are worse and effected symmetrically
Although she denies objective weakness, the pain is limiting her activities of daily living and frequently wakes her from sleep.
The stiffness lasts several hours in the morning. Otherwise, she is entirely well and has no medical history of note.
Examination
This elderly woman is uncomfortable and finds it difficult to move from the chair to the examining couch. She is generally
tender around the neck, shoulders and pelvic girdle. There is no evidence of synovitis but full range of movement is limited by
periarticular rather than true joint pain
Usually occurs in elderly patients, and it is more common in women.
aching and stiffness of the shoulder, neck, and hip-girdle area that can occur with giant
cell arteritis + flu-like symptoms
- Self-limited disease (duration of 1 to 2 years).
A significant minority of RA patients may present with a polymyalgia onset
Signs and symptoms:
1. Bilateral hip and shoulder muscle pain
Muran Mjahed 19
a. Often begins abruptly; but may be gradual
b. Stiffness in shoulder and hip after a period of inactivity
c. Pain occurs on movement; muscle strength is normal
d. Profound morning stiffness is common
2. Constitutional symptoms are usually present: malaise, fever, depression, recent weight loss, and fatigue
3. Joint swelling
a. some patients have synovitis in knees, wrists, or hand joints (similar to RA)
b. Synovitis and tenosynovitis around the shoulder may lead to rotator cuff tendonitis or adhesive
capsulitis
c. Signs and symptoms of temporal arteritis might be present
Pathogenesis:
age-related immune alterations in genetically predisposed subjects (associated with HLA-DR4 allele) contribute to development
of the disease.
But the true cause is yet to be determined.
Diagnosis:
1. Essentially a clinical diagnosis
2. ESR is usually elevated and aids in diagnosis
a. Almost always >50, frequently >100
b. Correlates with disease activity
3. Ultrasound, MRI of shoulders and hips in some cases
4. Funduscopic examination to monitor patients with associated giant cell arteritis
Treatment:
1. Low dose corticosteroids
a. Response usually occurs within 1 to 7 days.
b. Corticosteroids are not curative, but are effective in suppressing inflammation until the disease resolves
itself.
c. After 4 to 6 weeks, begin to diminish slowly.
d. Most patients can stop corticosteroids within 2 years. A few patients have symptoms for up to 10 years.
Differential diagnosis:
1. Polymyalgia rheumatica
2. Fibromyalgia (normal ESR, younger age at onset)
3. Infection
4. Rheumatoid arthritis
5. Hypothyroidism (elevated TSH, normal ESR and CRP)
6. Depression
7. Polymyositis
Complications of PMR:
- Giant cell arteritis
- Blindness in untreated GCA
Fibromyalgia
History
A 46-year-old woman is referred to the rheumatology department with a long history of muscle pain and fatigue. Her
symptoms developed insidiously and she now complains of pain ‘all over her body’, poor sleep and exhaustion much of the
time. She denies constitutional upset or specific symptoms but is finding it hard to work or care for her family. Her medical
history is unremarkable and she takes no regular medications.
Examination
Muran Mjahed 20
This woman is well and has no peripheral stigmata of inflammatory disease. Although her joints are mildly tender, there is no
evidence of synovial thickening or effusion. Palpation of a number of soft-tissue points is tender but her muscle strength is
preserved. All systems examinations are normal.
Occurs predominantly in adult women; due to imbalanced serotonin and dopamine hormones.
Chronic nonprogressive course with waxing and waning in severity.
noninflammatory syndrome of unknown etiology
Secondary fibromyalgia is not uncommon in patients with inflammatory disease such as
rheumatoid arthritis or SLE.
Presence of multiple trigger points that are tender to palpation aid with diagnosis; patients may cry
upon palpating these areas.
a. Symmetrical.
b. Eighteen characteristic locations have been identified, including occiput, neck,
shoulder, ribs, elbows, buttocks, and knees..
Fibromyalgia may coexist with depression.
Etiology is unknown—somatization is not a proven cause
Signs and symptoms:
1. Stiffness, arthralgia, body, musculoskeletal aches, fatigue.
a. Pain is constant and aching, and is aggravated by weather changes, stress, sleep deprivation, and cold
temperature. It is worse in the morning.
2. Sleep patterns are disrupted, and sleep is unrefreshing.
3. Anxiety and depression (psychiatric symptoms).
4. Headaches.
5. Paraesthesias.
6. Cognitive dysfunction.
7. Raynaud’s phenomenon
Tender points: occiput; trapezius, supraspinatus; gluteal; greater trochanter; low cervical; second rib; lateral epicondyle; knee
Pathogenesis:
Physical or emotional stress→ triggers central sensitization phenomenon→ dysfunction of neural-circuits→ transmission and
processing of afferent nociceptive stimuli→ manifestation of pain at the level of the locomotor system.
Fibromyalgia is not related to autoimmune response.
Diagnosis:
1. history of widespread pain (in all quadrants of the body) for at least three months and when pain is caused by
digital pressure in at least 11 out of 18 allogeneic points, called tender points.
2. no confirmatory tests for fibromyalgia, therefore, it is important to rule out: (differentials)
a. Myofascial syndromes
b. Rheumatoid disease
c. Polymyalgia rheumatica
d. Ankylosing spondylitis
e. Spondyloarthropathy
f. Chronic fatigue syndrome
g. Lyme disease
h. Hypothyroidism (thyroid disorders may lead to myalgias)
i. Polymyositis
j. Depression and somatization disorder
k. Hypertrophic osteoarthropathy
l. Hepatitis
m. Endocrine disorders
Muran Mjahed 21
Treatment:
3. Complete metabolic panels (ESR, CRP,CBC, TSH) should be performed routinely.
1.
2.
3.
4.
5.
Activity and engaging in low intensity exercise.
First-line treatment for fibromyalgia is amitriptyline.
Local anesthetic at trigger points.
Milnacipran and pregabalin (gabapentin)- SNRI or SSRI.
Cognitive behavioral therapy (CBT).
Ankylosing spondylitis
History
A 26-year-old man presents with a 6-month history of back and buttock pain and stiffness. His symptoms localize to his
lumbar spine and right buttock and are particularly marked first thing in the morning, but start to settle within a couple of
hours. The pain never spreads down the back of the leg and he has not noticed any change in sensation or loss of power. He is
otherwise fit and well, with the exception of two episodes of an acutely painful red eye for which he received ‘eye drops’ from
the ophthalmology service. He is self-employed with two children and smokes heavily.
Examination
This young man has dramatically reduced lumbar spinal movements in all planes but cervical movements are full and
pain-free. His right hip is irritable with reduced range of movement, particularly external rotation. There is a small effusion of
the left knee with evidence of Achilles tendinopathy and plantar fasciitis on the left foot. The remainder of his examination is
normal
→inflammatory spinal disease (spondyloarthropathy) and sacroiliitis
evidence of peripheral arthropathy, tendinopathy, possible extra-articular symptoms in the form of previous ocular disease, and
an elevated inflammatory response
Strong association with HLA-B27
Three times more common in male than in female patients
Bilateral sacroiliitis (inflammation of the sacroiliac joint) is a prerequisite for
making the diagnosis
Patients with back pain longer than 3 months, with age younger than 45 years at
onset.
It is characterized by “fusion” of the spine in an ascending manner (from lumbar
to cervical spine)
Early sacroiliitis in a patient with ankylosing spondylitis, indicated by prominent
edema in the juxta articular bone marrow (asterisks), synovium and joint capsule
(thin arrow), and interosseous ligaments (thick arrow) on a short tau inversion recovery (STIR) MRI
Course:
1. There is a slow progression, but acute exacerbations are common.
2. Life expectancy is unchanged.
3. The first 10 years of the disease can give an indication of long-term severity.
Signs and symptoms:
1. Low back pain and stiffness secondary to sacroiliitis.
2. limited motion in the lumbar spine.
3. Neck pain and limited motion in the cervical spine.
4. Enthesitis: inflammation at tendinous insertions into bone (usually occurs
in the heels; achilles tendon, and supraspinatus tendon)
5. Low back pain and stiffness are worse in the morning and better as the day
progresses. They improve with activity and a hot shower.
Muran Mjahed 22
6.
7.
8.
9.
10.
With extensive spinal involvement, the spine becomes brittle and is prone to fractures with minimal trauma.
Chest pain and diminished chest expansion; due to thoracic spine involvement
Shoulder and hip pain are most commonly in the peripheral joints
Constitutional symptoms—fatigue, low-grade fever, weight loss
Extra-articular manifestations
a. Eye involvement ;acute anterior uveitis
b. Cardiac (AV heart block and aortic insufficiency).
c. Renal involvement.
d. Pulmonary involvement.
e. Nervous systems.
11. Loss of lumbar lordosis
12. Dactylitis: sausage like fingers (usually associated with Crohn's disease)
Pathogenesis:
HLA-B27 belongs to the MHC-I surface protein encoded by the MHC B gene on chromosome 6.
HLA-B27→ peptide antigens to T immunocytes of the human body defense process→ inflammatory processes that are linked
to AS→ inflammation, bone erosion and syndesmophyte (spur) formation.
The inflammation leads to symptoms of pain and stiffness, while fibrosis and ossification at these sites generates signs of
increasing spinal restriction.
Diagnosis:
1. Schober’s test
2. Imaging studies of lumbar spine and pelvis (plain film, MRI, or
CT) reveal sacroiliitis and bamboo spine.
MRI highlights areas of high water content (joint inflammation and bone edema)
and shows features of AS: the corners of the lumbar vertebrae are ‘shiny’ with edema
and there is symmetrical inflammatory change at the sacroiliac joints with irregularity
of the joint space.
3. Elevated ESR in some patients due to inflammation
4. HLA-B27 is not necessary for diagnosis, and may be positive in
otherwise healthy persons.
Complications of Ankylosing Spondylitis:
1. Restrictive lung disease
2. Cauda equina syndrome
3. Spine fracture with spinal cord injury
4. Osteoporosis
5. Spondylodiscitis
Treatment:
1. Physical therapy; maintaining good posture, extension exercises.
2. NSAIDs; indomethacin.
3. Anti-TNF medications; etanercept, infliximab.
4. Surgery.
5. Patients who sustain minor trauma or complain of neck or back pain should be immobilized
to prevent spinal cord injury until imaging studies prove the opposite.
differential diagnosis of spondyloarthropathy:
1. Ankylosing spondylitis (prototypical spondyloarthritis), most common in males under 35 years of age
2. Psoriatic arthropathy
3. Enteropathic, associated with inflammatory bowel disease, but unrelated to disease activity
4. Reactive arthritis following genitourinary or gastrointestinal infection (in B27)
Muran Mjahed 23
Reactive Arthritis/Reiter Syndrome
History
A 41-year-old man presents to the rheumatology department with bloody diarrhea, ulcers over his shins and a painful, stiff
back. Although his back stiffness began more than 5 years ago, he chose to ignore it until recently when, in combination with
his other symptoms, he began to struggle to cope at home. His back pain and stiffness are worse in the morning and tend to
ease by lunchtime. It has, on occasion, been associated with a painful and swollen right knee. The diarrhea and leg ulcers
began six weeks previously and he is awaiting a gastroenterology outpatient appointment.
Examination
This man has limited spinal movement in all planes with a Schober’s test reduced at 19 cm. His right hip is irritable and there
is a moderate effusion of the right knee. There are two ulcers over his left shin with shiny yellow bases and red/blue
overhanging edges. The remainder of the examination is normal.
History
A 52-year-old man presents with a longstanding history of weight loss, diarrhea and painful, stiff hips and knees. The arthritis
developed first, affecting principally his hips and knees but tending to move around. A rheumatoid factor has been checked in
the past and was negative, so he felt reassured. The diarrhea then became an issue over the last 6 months; he has intermittent
abdominal pain and complains that the stools are foul-smelling and hard to flush away. There has never been any blood,
mucus or slime. With continuing diarrhea he has lost weight (5 kg in 6 months), despite a good appetite.
Examination
There is evidence of recent weight loss and a mild effusion of the right knee. Otherwise, system examination is normal.
History
A 28-year-old man presents to the emergency department with an acutely painful and swollen right knee. The symptoms
began 24 hours previously and have not responded to non-steroidal anti-inflammatory drugs (NSAIDs). He denies fever or
constitutional upset. His medical history is unremarkable, except for a self-limiting but severe diarrhoeal illness 3 weeks
previously.
Examination
This young man appears well but uncomfortable. His right eye has an injected sclera and there is a moderate effusion in his
right knee which is warm and displays reduced range of movement. He has a pustular rash on both heels. The remainder of
the examination is normal.
Inflammatory arthritis that develops after certain enteric or urogenital infections.
The term undifferentiated spondyloarthropathy is used when a patient has features of reactive arthritis but there is no evidence
of previous infection and the classic findings of Reiter syndrome are absent.
Reactive arthritis is asymmetric inflammatory oligoarthritis of lower extremities.
Reiter syndrome is an example of reactive arthritis, but most patients do not express the typical symptoms, which are: arthritis,
uveitis, and urethritis, so the term reactive arthritis is now used.
Presence of rash might suggest psoriatic arthritis; but the combination of rash, ocular
disease, self-limiting diarrhea and an acute monoarthropathy make reactive arthritis the
most likely diagnosis
Causative agents:
1. Enteric causes ; by shigella, salmonella, campylobacter, yersinia
2. Urogenital causes; by chlamydia trachomatis, HIV
Muran Mjahed 24
Signs and symptoms:
1. Infection of GI or genitourinary tracts 1 to 4 weeks prior to the onset of symptoms.
2. Asymmetric arthritis that progresses sequentially from one joint to another
3. Joints are painful, with effusions and lack of mobility that persist or recur over a long-term period.
4. Fatigue, malaise, weight loss, and fever are common.
5. Eye inflammation.
6. Enthesitis may be present.
7. Dactylitis and swollen fingers and toes
8. Onychodystrophy; Reiter’s nails
9. Characteristic skin rash; Keratoderma blennorrhagicum or syphilitic skin lesion
Seronegative arthritis may develop in up to 15 percent of patients with any form of inflammatory bowel disease, including
ulcerative colitis (UC), Crohn’s disease or microscopic and collagenous colitis. The most common clinical presentations are a
peripheral arthritis (commonly divided into type I and type II) and spondyloarthritis
- Type I enteropathic arthritis is an asymmetrical oligoarthritis which follows disease activity in the bowel.
● Whipple’s disease is a systemic illness caused by the Gram-positive bacillus Tropheryma whippelii
● Other IBS: crohns, ulcerative colitis, celiac disease
- Type II enteropathic arthritis is symmetrical and polyarticular; runs an independent course to bowel disease
Pathogenesis:
Recent infection→ triggers immune-mediated response→ T lymphocytes are activated by bacterial fragments→ activated
cytotoxic-T cells then attack the synovium and other self-antigens
anti-bacterial cytokine response is also impaired in reactive arthritis, resulting in the decreased elimination of the bacteria.
It occurs mostly in HLA-B27–positive individuals
The joint itself is not infected.
Diagnosis:
1. CBC, leukocytosis, Thrombocytosis, Increased serum Ig (previous infection), normocytic anemia
2. Cultures; blood, urine, stool, throat to detect any active infection
3. HLA-B 27+
4. Radiology; Sacroiliitis (if associated with AS), Enthesitis
5. MRI of the sacroiliac joints and lumbosacral spine
6. Send synovial fluid for analysis to rule out infection or crystals.
7. Endoscopy in case of enteropathic arthritis to exclude inflammatory bowel diseases.
As for all patients with a malabsorptive history, the investigations should also assess nutritional status, and calcium,
B12/iron/folate and vitamin D levels should be checked.
Treatment:
1. NSAIDs are first-line therapy.
2. DMARDs; sulfasalazine and immunosuppressive agents; azathioprine.
3. Antibiotic use is controversial; Azithromycin, Ciprofloxacin, Doxycycline
4. Intra-Articular Glucocorticoids
Septic arthritis
History
An 84-year-old woman with diabetes has been admitted to the emergency department with an acutely swollen and painful left
knee. She has been unwell with a raised temperature and productive cough for the last week and for the last 24 hours has been
unable to bear weight because of her knee pain.
Examination
Muran Mjahed 25
This elderly woman is unwell, sweaty and febrile. Her pulse is 108 bpm and blood pressure 98/60 mmHg. Oxygen saturation
in room air is 92 per cent. Her left knee is held rigid in fixed flexion and is hot and red with a moderate effusion. Her
respiratory rate is 22/min. There is decreased expansion on the right side, with dullness to percussion, increased vocal
resonance and coarse crackles at the base. The remainder of her examination is normal.
Chest X-ray Right basal consolidation
Acute infectious arthritis occurs when microorganisms (usually bacteria) invade the joint space (not the bone itself), where they
release endotoxins and trigger cytokine release and neutrophil infiltration. These inflammatory reactions ultimately lead to
erosion and destruction of the join
Risk factors for acute infectious arthritis.
1. Prior joint damage (e.g., rheumatoid arthritis).
2. Joint prosthesis
3. Concurrent or recent bacterial infection
4. immunocompromised (diabetes and old age)
5. extremes of age
Signs and symptoms:
1. The joint is swollen, warm, and painful.
a. The range of motion (active or passive) is very limited.
b. An effusion can be palpated.
2. Constitutional symptoms such as fever, chills, and malaise are common.
Pathogenesis:
microorganisms penetrate the joint via the following mechanisms:
a. Hematogenous spread—most common route.
b. Contiguous spread from another locus of infection (e.g., osteomyelitis, abscess, or cellulitis).
c. Traumatic injury to joints.
d. Iatrogenic (e.g., from arthrocentesis, arthroscopy)
Diagnosis:
1. Needle aspiration of synovial fluid
2. Blood cultures
3. Imaging (X-Ray, CT, MRI)
4. Joint aspirate (microscopy and culture) for possible septic arthritis
Treatment:
1. Antibiotic to treat the infection
2. Drainage of effusion
Differential diagnosis:
- Septic arthritis
- Osteoarthritis
- Gout
- Reactive arthritis
Psoriatic arthritis
History A 38-year-old man visits his general practitioner with a 2-month history of painful hands. It developed insidiously
over a few weeks and affects primarily the distal and proximal interphalangeal joints in his hands, the whole of his third toe on
the right foot and his right heel. The pain, stiffness and swelling are most marked in the morning but improve with exercise
and ibuprofen. His past medical history is unremarkable. Systemic enquiry reveals a longstanding rash which affects his
forearms and umbilicus for which he uses emollients. Examination There are plaques of scaly skin affecting his forearms, scalp
and umbilicus. His nails are dystrophic with pitting and ridging and there is soft-tissue swelling and synovitis affecting the
Muran Mjahed 26
distal and proximal interphalangeal joints. He has a ‘sausage toe’ on his right foot. His right Achilles tendon is swollen and
tender in its distal third, with pain on palpation of the insertion into the calcaneus.
Develops gradually in some patients with psoriasis (within 10 years).
Usually asymmetric and polyarticular.
Rash, nail and joint involvement are characteristic
Are the normal inflammatory markers unusual?
Psoriatic arthritis are part of group of disorders called seronegative spondyloarthropathy, like reactive arthritis; The
seronegativity (i.e. RF and ACPA negative) is also very supportive
Nail disease is very helpful in differentiating psoriatic arthritis from other forms of inflammatory arthropathy.
Signs and symptoms:
1. Dactylitis and tendonitis
2. Predilection for DIP and PIP joints (MCP are less
commonly affected. Distal and proximal polyarticular
diseases).
3. Joint pain, stiffness and swelling.
4. Onycholysis and nail pitting
5. Upper extremities are more common to be involved than
lower extremities; smaller joints are more common than
large joints.
6. Oligoarthritis (particularly hips and knees)
7. Anterior uveitis
8. Sacroiliitis and/or spondyloarthropathy.
Pathogenesis:
Dendritic cells (DC)→ produce and secrete IL-23 and IL-12 → result in enthesitis → stimulate Th17→stimulate the production of
inflammatory cytokines → IL6, IL17, IL22 → IL17 derives synovial fibroblasts, and macrophages to promote inflammatory
cytokines (IL1B, IL16, TNF) that promote bone destruction → IL22 is responsible for production of new bones.
Diagnosis:
1. Labs
a. CRP / ESR; correlates with disease activity.
b. HLA B-27 +
c. Hyperuricemia.
2. Radiographs
a. Periostitis
b. Ankylosis
c. Osteolysis
d. Dactylitis
no diagnostic test and often the acute phase is not as marked as in other inflammatory joint diseases.
Radiology is unhelpful early on: the periarticular osteopenia of rheumatoid is characteristically absent and the classic osteolysis
leading to ‘pencil-in-cup’ deformities is a late feature.
Tendinopathy, enthesopathy, plantar fasciitis, sacroiliitis and spondyloarthropathy may be evident on MRI
Treatment:
1. Initial treatment is NSAIDs,
2. Methotrexate or antiTNF agents for persistent arthritis.
3. Steroids are typically not used.
Differential diagnosis of the rash and arthropathy:
1. Psoriatic arthritis
2. Systemic lupus erythematosus
Muran Mjahed 27
3. Vasculitis
4. Sarcoidosis
5. Enteric arthropathy
Juvenile arthritis
History
A six-year-old girl is brought to her general practitioner by her mother, with an 8-week history of a stiff and painful swollen
right knee. There is no recall of trauma and she is otherwise well, with no recent history of infectious illness. Her medical
history is unremarkable and her vaccinations are all up to date. A course of a non-steroidal antiinflammatory drug (NSAID)
has been of minimal benefit.
Examination
The girl is uncomfortable getting undressed and on to the examination couch. There is no peripheral stigmata of
inflammatory disease, but she has a moderate effusion of the right knee, which is warm and shows reduced flexion.
Juvenile arthritis is a long-lasting, chronic disease. It is the most common form of arthritis in children.
The three main types of juvenile arthritis are:
1. oligoarticular arthritis (<5 joints; subdivided into persistent and extended)
2. polyarticular arthritis (>5 joints; subdivided into RF positive and RF negative)
3. systemic-onset JIA
4. enthesitis-related arthritis (linked to the presence of HLAB27)
5. psoriatic arthritis
Signs and symptom:
1. Painful joints in the morning that improve by afternoon, the first sign of the disease
is a morning limp, caused by an affected knee.
2. Joint swelling and pain may also be noted, a child may feel irritable or tired and not
want to play.
3. Sometimes, it causes lymph node swelling in the neck (cervical lymphadenopathy) or
in other parts of the body.
4. Anterior uveitis with oligoarticular disease
anterior uveitis may be asymptomatic, early referral to ophthalmology services for slit-lamp examination is recommended
The risk of developing anterior uveitis is increased in patients with high ANA
Diagnosis:
1. Children under 16 years
2. Swelling pain stiffness growth problem
3. Eye problem
4. ↑ESR, ↑ CRP
5. Positive ANA
6. Negative RF
Treatment:
1. NSAID
2. DMARD; methotrexate
3. Corticosteroids
4. Surgery
Muran Mjahed 28
Inflammatory Myopathies
History
A 72-year-old woman is admitted by the medical team with muscle weakness and pain. Her symptoms began insidiously over
the last few weeks, but are now so severe she finds it hard to climb stairs or raise her arms above her head. Fine movements and
grip strength are unaffected. She has also noticed a scaly rash over the back of her hands and her palms are becoming cracked
and unsightly. Otherwise she is well, with no medical history of note. Systems review is unremarkable; she denies weight loss
and in fact has noticed that her abdomen is mildly swollen.
Examination
This elderly woman has marked proximal weakness, graded 2 to 3 out of 5 at shoulder and hip in the absence of neurological
features. She has a lilac discolouration over the back of her eyes, a scaly rash on the back of her fingers and papules over her
metacarpophalangeal (MCP) joints. Her palms are fissured and cracked and nail-beds are ragged with dilated nailfold capillary
loops. Cardiorespiratory examination is unremarkable. Abdominal examination reveals a non-tender pelvic mass and a small
amount of ascites.
Autoimmune condition that involves proximal muscle weakness and muscle inflammation.
Classification:
a. Polymyositis.
b. Dermatomyositis.
- The only difference between them both is that polymyositis does
not involve the skin; however, skin is involved and develops skin
rash in dermatomyositis.
Females are more likely to be affected than males, 2:1 ratio, with age at onset 40-50
Dermatomyositis associated with malignancy often remits once the tumor is removed
Weakness
Causes:
Genetic predisposition (HLA 8,1 PTPN22, STAT4, TRAF6)
Environmental triggers (UV radiation, smoking, previous infection, previous lung disease,
occupational exposure, medication, dietary supplements).
Signs and symptoms:
1. Symmetrical proximal muscle weakness
2. Most severely affected muscle groups are the neck flexors, shoulder girdle, and pelvic girdle
muscle. (in a majority of patients)
3. Distal extremity weakness is less frequent and typically less severe
4. Difficulty with:
a. Walking up the stairs.
b. Sitting up from a chair
c. Reaching for items on shelves and cupboards.
5. Myalgia in a minority of patients.
6. Dysphagia; involvement of striated muscle in the upper GI tract in a minority of patients
Associated findings include (other autoimmune conditions)
a. Interstitial lung disease.
b. CHF
c. Conduction defects.
d. Raynaud's phenomenon.
e. Polyarthritis and arthralgias.
f. SLE .
7. Features unique to dermatomyositis; skin findings which can occur at the same time with myalgia:
Muran Mjahed 29
Pathogenesis:
a.
Diagnosis :
Dermatomyositis: humoral immune mechanisms; involvement of B and CD4 cells leading to perifascicular
vascular abnormalities, around the muscle.
b. Polymyositis and inclusion body myositis: cell-mediated process; involvement of CD8 cytotoxic T cells; which
cause damage to muscles directly.
- Both cause damage and necrosis of muscles
1.
2.
3.
4.
5.
6.
7.
8.
9.
Treatment:
a. Heliotrope rash → a lilac discoloration of the back of the eyes
b. Rash similar to malar rash in lupus.
c. Gottron papules; papular, erythematous, scaly lesions over the knuckles (MCP, PIP, DIP)→
pathognomonic for dermatomyositis (diagnostic).
d. V sign; rash on the face, neck, and anterior chest, similar to Shawl, but occurs on the anterior area of
the neck
e. Shawl sign; hyperpigmented rash on shoulders and upper back, elbows, and knees.
- Both V and shawl signs occur due to exposure to sun
f. Holster sign; hyperpigmented rash on the lateral thighs
g. Periungual erythema with telangiectasia
h. Vasculitis of GI (swelling of the abdomen), eyes, kidneys and lungs
i. Calcinosis cutis: Subcutaneous calcifications in children; painful
j. There is an increased incidence of malignancy in older adults (lung, breast, ovary, GI tract, and
myeloproliferative disorders)
Clinically; presence of rash on the face and palms
CK level is significantly elevated due to muscle necrosis.
LDH, aldolase, AST, ALT are also elevated (muscle waste products).
ANA in majority of cases
Antibodies (anti-Jo-1 antibodies, anti Mi, anti SRP)—abrupt onset of fever, cracked hands, Raynaud
phenomenon, interstitial lung disease and fibrosis, arthritis
EMG; abnormal in most patients
CT and X-ray to exclude underlying malignancy
T2 weighted MRI helpful in identifying areas of swelling and aids in taking biopsy
Muscle biopsy
a. Shows inflammation and muscle fiber fibrosis and necrosis.
b. Red rimmed vacuoles with beta amyloid
c. Dermatomyositis→perivascular and perimysial
d. Polymyositis and inclusion body myositis→endomysial
1. Corticosteroids.
2. Steroid-sparing immunosuppressive agents:
a. Methotrexate.
b. Azathioprine.
3. Hydroxychloroquine.
4. Physical therapy.
5. vitamin D and calcium supplementation may be required to protect bones.
Differential diagnosis:
a. Inflammatory myopathy; Poly- and dermatomyositis
b. Drug-induced myopathy; colchicine, alcohol
c. Neuromuscular disease; myasthenia gravis
d. Endocrine disease; Cushing’s and Addison’s disease
e. Metabolic disease; Glycogen storage disorders
f. Rheumatic disorders; Polymyalgia rheumatica, fibromyalgia
Muran Mjahed 30
Giant cell arteritis
History
A 62-year-old man presents to his general practitioner with a headache. The pain focuses over the temporal areas, where his
scalp also feels tender such that he finds it painful to lie on his side at night. Over the same period as his headache has
developed, he has noticed pain and fatigue in his jaw when chewing his food. He is otherwise ‘reasonably well’ but has been
experiencing pain and stiffness in his shoulders and hips which he has attributed to heavy gardening, and has lost a few
kilograms in weight. His past medical history and systems enquiry is unremarkable and he takes no regular medication.
Examination
This man appears well but uncomfortable. He has marked tenderness to even light touch over his temples; his temporal
arteries are tender and pulseless bilaterally. Fundoscopy and the rest of his physical examination are normal.
Also called temporal arteritis.
granulomatous vasculitis of unknown cause; it is T Cell mediated immune response. typical patient is >50 years of age; twice as
common in women as men
The temporal arteries are most frequently affected, but it may involve other arteries, such as the aorta or carotids.
Carotid bruits, decreased pulses in the arms, and aortic regurgitation may also be observed.
Associated with increased risk of aortic aneurysm and aortic dissection
Microscopically there is inner media granulomas
Keys to Diagnosing Temporal Arteritis
- Age >50 years
- New headache
- Tender/palpable temporal artery
- High ESR
- Jaw claudication
Signs and symptoms:
1. Constitutional symptoms of malaise, fatigue, weight loss, and low-grade fever
2. Headaches which may be severe
3. Visual impairment
a. Caused by involvement of ophthalmic artery
b. Optic neuritis; amaurosis fugax; may lead to blindness in up to 50% if not treated early and aggressively
4. Jaw pain with chewing, intermittent claudication of jaw when chewing
5. Tenderness over temporal artery; absent temporal pulse
6. Palpable nodules
7. Forty percent of patients also have polymyalgia rheumatica
Pathogenesis:
The pathophysiology is not well understood
intimal hyperplasia and luminal obstruction leading to ischemic manifestations involving extracranial branches of carotid arteries
and aorta involving all layers of the arterial wall
Macrophages in the adventitia produce pro-inflammatory cytokines such as IL-1, IL-6 and tumor necrosis factor α. These
cytokines promote arterial wall and systemic inflammation. )
Diagnosis:
1. Clinically
2. ESR elevated (high ESR may precipitate blindness)
3. Biopsy of the temporal artery.
- A single negative biopsy does not exclude the diagnosis.
4. Angiography in cases of large vessels involvement
5. Examination of the ophthalmic artery (ciliary branch)
Muran Mjahed 31
Diagnostic triad: anemia, fever, ESR
On biopsy: temporal artery inflammation is segmental, granulomas will be visible
Treatment:
1. Use high-dose steroids (prednisone) early to prevent blindness, before the biopsy results.
a. If visual loss is present, admit the patient to the hospital for IV steroids; otherwise, start oral
prednisone
b. If the diagnosis is confirmed, continue treatment for at least 4 weeks, then taper gradually, but
maintain steroid therapy for up to 2 to 3 years. Relapse is likely to occur if steroids are stopped
prematurely
2. Follow up on ESR levels to monitor effectiveness of treatment.
3. Visual loss in one eye may be temporary or permanent; treated by steroids.
- Methylprednisolone within 24 hours restores vision.
4. Bone protection with bisphosphonates and calcium/vitamin D supplementation
Even if untreated, the disease is usually eventually self-limiting in most patients, although vision loss may be permanent
Takayasu arteritis
History
A 24-year-old Asian woman presents to her general practitioner with dramatic weight loss and intermittent fever. Her
symptoms have been present for several weeks, but over the last few days she has developed difficulty walking. Although
previously very fit and active, she can now walk only a quarter of a mile before developing fatigue and cramping pain in her
calves that forces her to stop. Once she has rested for a while, she is able to continue walking again, but the symptoms return.
Examination
This young woman is well but her GP is unable to detect a blood pressure from the left arm: the pulses are absent on that side
and a subclavian bruit is clearly audible. The opposite arm is normal. Further examination of her vascular system reveals
another bruit over her right femoral artery with decreased pulses distally on the same side. The rest of her pulses are present
and the remainder of her physical examination is normal
Suspect Takayasu arteritis in a young woman with:
1. Decreased/absent peripheral pulses
2. Discrepancies of BP (arm vs. leg)
3. Arterial bruits
Most common in Asian women younger than 50 years of age.
Granulomatous vasculitis of aortic arch and its major branches, leading to fibrosis and causing to
stenosis or narrowing of vessels
Signs and symptoms:
1. Constitutional symptoms; fever, night sweats, malaise, arthralgias, fatigue.
2. Pain and tenderness over involved vessels.
3. Absent pulses in carotid, radial, or ulnar arteries; aortic regurgitation may be
present.
4. ischemia develops in areas supplied by involved vessels.
5. Severe complications include
a. limb ischemia
b. aortic aneurysms
c. aortic regurgitation
d. stroke
e. secondary HTN due to renal artery stenosis.
6. Causes visual disturbances due to ocular involvement and hemorrhage of retinal arteries
Muran Mjahed 32
7. Visual and neurological symptoms
8. Claudication
Pathogenesis:
The inflammatory lesions in Takayasu's arteritis originate in the vasa vasorum and are followed by cellular infiltration, mainly
composed of T cells (gammadelta lymphocytes, cytotoxic T lymphocytes, T helper cells), but also of natural killer cells, dendritic
cells, monocytes and granulocytes, invading the outer layer of the media and/or its neighboring adventitia.
interleukin-6, interleukin-1 are released in large amounts by infiltrating inflammatory cells within damaged tissue, as well as by
circulating inflammatory cells, and very likely help maintain the aberrant immune activation, by promoting endothelial cells
activation and by inducing lymphocyte infiltration.
Diagnosis:
1. Arteriogram.
2. Check for granuloma (may be present in some cases).
3. Elevated ESR and CRP.
4. CBC; Anemia, low hematocrit, thrombocytosis.
5. Elevated Serum Creatinine.
6. MRI and Urinalysis; Proteinuria, Hematuria if complicated
Treatment:
1. High dose steroids; prednisone.
2. Treat HTN.
3. Cyclophosphamide is for those who do not achieve remission with standard therapy
4. Surgery or angioplasty may be required to recannulate stenosed vessels. Bypass grafting is sometimes necessary
Polyarteritis nodosa (PAN )
History
A 63-year-old man presents to his general practitioner with painful hands. His hands have been stiff and sore for several
months but he denies frank swelling. The arthralgia is associated with a ‘blotchy rash’ over his trunk, profound fatigue and
weight loss. In addition, he has experienced bouts of testicular pain and over the last 48 hours has developed central
abdominal pain after each meal.
Examination
This man has evidence of recent weight loss and a blue/purple net-like rash over his abdomen and thighs. His joints are tender
but there is no clinical evidence of synovitis. Genitourinary examination is unremarkable and he has mild abdominal
tenderness to deep palpation but no organomegaly. The remainder of the examination is unremarkable.
Symptoms involve the nervous system and GI tract.
Can be associated with hepatitis B, HIV, and drug reactions.
Necrosis is segmented, leading to “rosary sign” as a result of aneurysms.
Affects young to middle-aged individuals.
Has an overall poor prognosis.
Signs and symptoms:
1. Early symptoms are fever, weakness, weight loss, myalgias,
arthralgias, and abdominal pain (bowel angina).
2. HTN
3. Mononeuritis multiplex.
4. Livedo reticularis (purpura)
5. Glomerulonephritis is rare
6. Testicular pain
7. GI bleeding
Muran Mjahed 33
8. Active hepatitis B (uncommon)
9. No pulmonary involvement (distinguish it from GPA)
Pathogenesis:
PMN invasion of all layers → fibrinoid necrosis → intimal proliferation → reduced luminal area→ ischemia, infarction, and
aneurysms.
Diagnosis:
1. biopsy of involved tissue or mesenteric angiography.
2. ESR is elevated, ↑BUN, and p-ANCA may be present.
3. Test for fecal occult blood.
Treatment:
1. Start with corticosteroids.
2. If severe, add cyclophosphamide to prevent interstitial ischemia
3. Plasmapheresis for patients with HBV
Kawasaki disease
Affects children younger than 5 years of age.
More prominent in children of asian background; Japan/China > Europe
A self-limiting disease.
Stages:
1. Acute; 1-2 weeks
2. Sub acute; 2-8 weeks
3. Chronic; longer than 8 weeks
Cause is Infection/Genetic trigger
1. Signs and symptoms:
2. Symptoms mimic viral infection; misdiagnosed in most cases.
3. Can be fatal with coronary artery aneurysms (in cases of subacute, echocardiogram is required).
4. Thrombosis with myocardial infarction (if subacute CAD was not treated).
5. CRASH & BURN
a. Conjunctivitis
b. Rash
c. Adenopathy; enlargement of cervical lymph nodes
d. Strawberry tongue; Oral mucositis
e. Hand/Foot Changes; Erythema, Edema
f. Fever >5 days
Differential diagnosis include:
Scarlet fever (someone exposed to group A strep to become sick with strep throat or scarlet fever, illness usually begins with a
fever and sore throat)
Diagnosis:
1. clinical evaluation; no specific diagnostic technique
2. CBC; CRP/ESR
3. Urinalysis; may show pyuria /proteinuria
4. ECG/Echo; for cardiac abnormalities
Treatment:
1. Refer to Pediatrician
2. High dose aspirin for Fever; (Reye’s disease may develop)
3. IVIG to Prevents coronary artery aneurysms
4. Disease is self-limiting
Muran Mjahed 34
Granuloma with polyangiitis, GPA (Wegener Granulomatosis)
History
A 58-year-old woman is admitted to the emergency department with haemoptysis. She has been non-specifically unwell with
recurrent low-grade fever, non-productive cough and weight loss for the last few weeks but is now ‘exhausted’ and short of
breath on exertion. Her general practitioner had done some blood tests and commenced oral antibiotics with no benefit and
she has been coughing up blood for 24 hours. Her medical history includes type 2 diabetes for which she takes metformin.
She is a smoker with a 20-pack per year history and is teetotal.
Examination
This woman looks unwell and sounds nasally congested. She is not febrile. Pulse rate is 88/min, blood pressure 145/92 mmHg
and oxygen saturations 95 percent on room air. There are fine inspiratory crackles in the mid and lower zones of the chest, but
cardiovascular and abdominal examination is unremarkable.
ANCA-associated Vasculitides (usually c-ANCA positive).
Necrotizing granulomatous vasculitis.
Occurs in older individuals, and predominantly in caucasians.
Etiology is yet to be identified.
Signs and symptoms:
1. Constitutional symptoms (fever, weight loss, fatigue)
2. Ear, Nose, Throat:
a.
Rhinosinusitis
d. Epistaxis
b. Oral and nasal ulcers
e.
c. Otorrhea
Otitis media
3. Lower respiratory tract:
a.
Cough
d. Dyspnea
b. Hemoptysis
c. Interstitial lung disease
e.
f.
Pleuritic chest pain
Pulmonary nodules
4. Renal system:
a.
Asymptomatic hematuria
b. ↑ creatinine
c. Glomerulonephritis
b. Livedo reticularis
c. Urticaria
d. Secondary nephritic syndrome
5.
Cutaneous:
In half of patients.
a.
Leukocytoclastic angiitis
d. Erythema nodosum
6.
7.
8.
9.
10.
Eye involvement: conjunctivitis or scleritis.
Arthralgias and myalgias.
Heart involvement: pericarditis, myocarditis.
Neurologic findings: sensory neuropathies
Tracheal stenosis.
Muran Mjahed 35
The classic triad of Wegener’s granulomatosis is the presence of upper and lower respiratory tract disease and renal impairment.
Pathogenesis:
anti-neutrophil-cytoplasmic-antibody (c-ANCA) associated vasculitides (AAV).
The granulomas in GPA begins→ formation of neutrophilic microabscesses→ partial or total occlusion of blood vessels→ the
granulomas in GPA are not well-formed→ consist of giant cells surrounded by plasma cells, lymphocytes, and dendritic cells→
that damage the submucosa and penetrate the surrounding tissues, cartilage, or bone→ necrosis and permanent deformities.
Diagnosis:
1. CXR→ nodules and infiltrates
2. Urinary sediment → microscopic hematuria
3. Biopsy of artery or perivascular area → granulomatous formation (gold standard) or lung biopsy.
4. Labs → ↑ ESR, anemia, positive c-ANCA, proteinase a 3, thrombocytopenia.
Treatment:
1. cyclophosphamide and corticosteroids combination.
2. Immunosuppressants.
3. oral trimethoprim/sulfamethoxazole for upper respiratory tract infection and kidney impairment
4. Consider renal transplantation if the patient has end-stage renal disease (ESRD).
Prognosis is poor, patients die within a year
Eosinophilic Granulomatosis With Polyangiitis (EGPA )
History
A 45-year-old woman presents to the emergency department unable to lift her right foot. She was well the night before and
noticed the problem immediately on waking in the morning; she came straight to hospital as she was frightened she was
having a stroke. Her past medical history reveals poorly controlled adult-onset asthma for which she takes inhaled steroids and
beta-agonist, and persistent rhinitis for which she uses nasal spray. She has no cardiovascular risk factors. She takes no oral
medication and has no other relevant medical or family history. Her only foreign travel was a two-week holiday in Menorca 4
years ago. She does not smoke or drink.
Examination
This woman is well and not febrile. She walks with a high-stepping gait on the right side to avoid her toes dragging on the
floor. She has weakness of dorsiflexion and eversion of the foot, with some reduced sensation over the top of the foot. There is
a non-blanching rash over her legs which she reports has been present for a week and is gradually deteriorating. The remainder
of her examination is normal.
Known as Churg–Strauss Syndrome, and allergic granulomatosis.
A multi system disorder, causing granulomatous inflammation of both, small and medium sized arteries.
Key to diagnosis: hypereosinophilia and tissue infiltration of eosinophils
Genetic predisposition plays a role in the formation of EGPA.
Leukotriene receptor antagonists also play an important role in the development of EGPA.
Patients may be first misdiagnosed with allergies.
5-year survival rate
Stages:
1. Prodromal stage
a. Occurs in 20s and 30s.
b. Atopic disease with allergic rhinitis and asthma.
2. Eosinophilic stage
a. Hypereosinophilia.
b. Organs begin to become infiltrated with eosinophils.
3. Vasculitic stage
Muran Mjahed 36
a. Occurs in 30s and 40s.
b. Most of the signs and symptoms develop in this stage.
c. Granulomatous inflammation of small and medium sized vessels.
Classic triad of EGPA:
1. Asthma and allergic rhinitis
2. Eosinophilic lung disease similar to pneumonia
3. Systemic vasculitis
a. Mononeuritis multiplex
b. Peripheral neuropathy
c. Peripheral eosinophilia
Signs and symptoms:
1. Lung involvement:
a. Athma, dyspnea
b. Pleural effusion
c. Pulmonary opacities on imaging
2. Ear, Nose, Throat
a. Otitis media
b. Recurrent sinusitis
c. Allergic rhinitis
d. Polyps in the nasal canal
3. Peripheral neuropathies in most patients
4. Eosinophilic gastroenteritis
a. abdominal pain
b. Melena or hematochezia
c. Diarrhea
5. Skin lesions
a. Subcutaneous nodules that are often tender
b. Palpable purpura
6. Cardiac involvement which posses an increased risk of mortality
a. Pericarditis
b. Hypertension
7. Renal involvement:
a. Hematuria
b. Oliguria
c. Kidney injury
8. Constitutional symptoms are most prominent during the Vasculitic stage.
Pathogenesis:
EGPA is typically considered a Th2-mediated disease and blood and tissue eosinophilia represent the cornerstone of diagnosis.
Besides, ANCA are known for inducing endothelial injury and vascular inflammation by activating the circulating neutrophils.
Diagnosis:
1. Eosinophilic count >1500/ microL.
2. p-ANCA positive in a majority of cases.
3. ↑IgE levels, MPO-ANCA
4. CXR to identify any pulmonary opacities
5. Biopsy of lung or skin tissue shows prominence of eosinophils.
Treatment:
1. Systemic glucocorticoids
2. Cyclophosphamide and rituximab
3. Patients with life threatening diseases are treated with plasmapheresis.
4. Azathioprine and methotrexate for maintenance.
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Microscopic Polyangiitis
A small vessel disease, similar to GPA. The only difference is that microscopic polyangiitis does not
involve the nose.
Signs and symptoms:
1. Skin involvement →palpable purpura
2. Lungs → cough, dyspnea, hemoptysis, pulmonary fibrosis, pulmonary
hypertension, but less commonly involved.
3. kidneys →glomerulonephritis
Diagnosis:
Can also be distinguished from GPA by biopsy, which shows necrotizing vasculitis without
granulomas
Treatment:
1. Systemic glucocorticoids
2. Cyclophosphamide and rituximab
3. Patients with life threatening diseases are treated with plasmapheresis.
4. Azathioprine and methotrexate for maintenance.
Familial Mediterranean Fever
History
A 16-year-old Turkish boy is seen in the emergency department with abdominal pain and fever. His right knee is also
exquisitely tender and slightly swollen. He has suffered recurrent attacks with a similar presentation since childhood, although
normally they are more severe and also include pleurisy. He has been told that ‘it runs in the family’. The attacks resolve
spontaneously and in between times he is entirely well.
Examination
This adolescent is very uncomfortable, with a temperature of 38.8°C. His pulse rate is 110/min, blood pressure 115/63
mmHg. He has marked abdominal tenderness with rebound and guarding; his bowel sounds are reduced. There is a mild and
cool effusion of his right knee, which is extremely tender. The rest of his examination is normal.
FMF is an autosomal recessively inherited periodic syndrome characterized by stereotyped attacks of fever and inflammatory
features which last up to 4 days and then remit spontaneously
The combination of recurrent serositis (peritonitis and pleurisy), fever and eastern Mediterranean origin raises the possibility of
familial Mediterranean fever (FMF) as the underlying diagnosis
The arthritis is classically monoarticular and symptoms often outweigh the signs, with
extreme tenderness despite only mild effusions and a marked absence of increased
temperature
Signs and symptoms:
1. fever
2. peritonitis
3. arthritis
4. pleuritis
5. rash (erysipelas-like).
Diagnosis:
1. Check for acute abdomen - CBC, inflammatory markers, amylase and lipase,
lactate (severe disease)
2. Abdominal and chest X-ray
3. Genetic testing
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Complications:
- Amyloidosis
a multisystem disease caused by the deposition of insoluble protein in the extracellular matrix: renal, cardiac and hepatic tissues
are commonly affected.
Primary amyloid (AL): deposition of immunoglobulin light chains and occurs in isolation or in the context of myeloma.
Secondary or reactive amyloid (AA): deposition of amyloid A rather than light chains and may complicate any chronic infective,
malignant or inflammatory process such as FMF.
Treatment:
Colchicine (diminishes the attacks for serositis and reduces the inflammation and pain)
It is not only very effective at diminishing the attacks of serositis in FMF, but has also been shown to reduce the development of
renal amyloidosis in these patients by up to two-thirds.
Mononeuritis multiplex
History
A 64-year-old man is referred urgently by his general practitioner with acute neuropathy. Two days prior to presentation the
patient awoke to find himself unable to lift his right foot and toes while walking, such that he kept tripping. Over the next 24
hours he found he had lost control of his left thumb and could not grip things properly. His problems were associated with
altered sensation in his hand and foot. His past medical history is entirely unremarkable.
Examination
This man has a high steppage gait and inability to dorsiflex the right foot and walk on his heels only. Sensation is also
diminished over the top of the foot and ankle. In the left hand, there is loss of abduction and opposition of the thumb and
reduced sensation in the lateral three and a half digits.
Mononeuritis multiplex can be caused by any of the medium or small vessel vasculitis
Signs and symptoms:
1. livedo reticularis
2. back pain
3. testicular pain in polyarteritis nodosa
4. sinus or audiovestibular disease in Wegener’s granulomatosis
5. adult-onset asthma or nasal polyps in Churg–Strauss syndrome
6. abdominal pain and rectal bleeding in Henoch–Schönlein vasculitis.
Diagnosis:
- nerve biopsy and a common site for this procedure is the sural nerve
Treatment:
1. potent immunosuppression
- high-dose corticosteroids and cyclophosphamide
2. treatment of underlying infections such as hepatitis
3. Patients with foot drop will also require orthoses and physiotherapy to maximize physical function.
Mixed Connective Tissue Disease (MCTD)
History
A 44-year-old woman presents to the rheumatology department with a constellation of symptoms. She was well until 8
months ago when she developed Raynaud’s phenomenon and joint pains. The latter responded to a non-steroidal
anti-inflammatory drug (NSAID), so she ‘got on with normal life’. Over the last few months she has noticed the skin over her
fingers becoming tighter. In recent weeks she has developed muscle weakness such that she finds it difficult to climb stairs or
get out of a chair unaided.
Muran Mjahed 39
Examination
There is some skin tethering over the fingers, with reduction in the finger pulps. Although her joints are painful there is no
objective evidence of synovitis. Proximal muscle power is reduced to 3/5. Respiratory examination reveals fine inspiratory
crackles bibasally, but the remainder of her examination is normal. The general practitioner who referred her performed an
‘autoimmune screen’.
Mixed connective tissue disease is an “overlap” syndrome with clinical features similar to those of SLE, RA, systemic sclerosis,
and polymyositis.
Findings consistent with each of these diseases do not necessarily occur simultaneously. It usually takes some time for a pattern
to be identified and a diagnosis of mixed connective tissue disease to be made.
Features seen in RA, SLE, myositis and scleroderma in the presence of anti-U1-RNP antibodies
Signs and symptoms:
1. joint symptoms
2. Raynaud’s phenomenon
3. Sclerodactyly
4. proximal myopathy
5. Other frequent problems include esophageal dysmotility, serositis and lymphadenopathy
Diagnosis:
1. presence of anti-U1-RNP Abs
2. High ANA and RF
Treatment:
- Depends on the predominant underlying disease.
Cryoglobulinemia
History
A 78-year-old woman is referred from a leg-ulcer clinic to rheumatology for advice. She has been treated with compression
bandaging for presumed venous ulcers for several months, with no perceptible benefit, and on a recent review was found to
have a few scattered lesions of palpable purpura, an elevated ESR and a very high rheumatoid factor.
Examination This woman has palpable purpura over her feet and toes, with a shallow painful ulcer on her left shin and one
over her right first metatarsophalangeal (MTP) joint. The edges of the ulcers are punched out but not heaped up, and the
bases are clean with no evidence of infection. There is no clinical evidence of synovitis and the remainder of the examination is
normal.
Caused by deposition of cryoglobulins, which are immunoglobulins that precipitate in cold temperatures.
Some cryoglobulins have rheumatoid factor activity, giving rise to a very high RF titre in the absence of rheumatoid arthritis
Classified into Type I, Type II, and Type III based on the type and clonality of immunoglobulins
Causes:
1. Chronic HCV infection- most common cause
2. Chronic HBV infection
3. HIV infection
4. Other causes of liver disease (autoimmune hepatitis, primary biliary cirrhosis)
Cryoglobulinemia exist in single and mixed forms
a. A single homogeneous form (25 percent), also known as type I, can be essential or idiopathic, but is often
associated with myeloma, lymphoma or Waldenström’s macroglobulinemia
b. The mixed form (75 per cent) is further subdivided into mixed monoclonal (type II) and polyclonal (type III),
and both types may form complexes with self IgG (i.e. have rheumatoid factor activity).
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Although mixed cryoglobulinemia can be essential, type II is often associated with myeloma, lymphoma,
Sjögren’s syndrome and infections (particularly hepatitis C).
Type III is classically associated with autoimmune inflammatory disease (particularly RA and SLE)
Signs and symptoms:
1. palpable purpura
2. renal disease
3. arthralgias/arthritis
4. peripheral neuropathy
5. Hypocomplementemia ( low serum levels of C3 and C4)
6. Pulmonary and CNS involvement are rare
Palpable purpura may occur in conditions such as meningococcal sepsis and thrombocytopenic purpura, but one of the most
common inflammatory causes of palpable purpura is vasculitis. The most common underlying conditions are
Henoch–Schönlein purpura, leukocytoclastic vasculitis and cryoglobulinemia
Complications:
1. Cutaneous with palpable purpura, petechiae, distal ulceration/necrosis and livedo
2. Raynaud’s phenomenon
3. Arthritis
4. Peripheral neuropathy
5. Renal disease (should check renal function and blood pressure, along with a urine dip checking for proteinuria
or haematuria)
6. Liver disease
Pathogenesis:
Proposed mechanism is deposition of antigen-antibody complexes (such as HCV antibodies) in small vessels → complement
activation and inflammation.
Liver disease may contribute to decreased immune complex clearance,→ greater tissue deposition and disease activity.
Diagnosis:
1. clinically
2. circulating cryoglobulins levels ( measuring can be challenging as significant quantities are lost when the blood
cools to below 37°C)
3. biopsy →leukocytoclastic vasculitis (inflammation with polymorphonuclear leukocyte nuclear debris).
4. Patients should be tested for underlying HCV, HBV (serology), and HIV.
Treatment:
- depends on the extent of disease and the association with hepatitis C.
- If not associated with hepatitis:
1. Cold avoidance
2. NSAIDs
3. Hydroxychloroquine
4. Corticosteroids and steroid-sparing agents such as azathioprine
5. Cytotoxic therapy (cyclophosphamide) or plasmapheresis is for organ or life-threatening disease
- Hepatitis associated cryoglobulinemia
1. interferon-a with or without the antiviral ribavirin
2. immunosuppressive agents if the vasculitis is very severe
- If asymptomatic: only monitoring is required
- If mild to moderate: low dose corticosteroids
- If moderate to severe: INF, ribavirin - medium dose corticosteroids
- If severe: plasmapheresis
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Buerger disease
History
A 17-year-old youth is referred urgently to the rheumatology department with a rapidly progressing rash over his buttocks and
legs, and severe, cramping abdominal pain. The rash began as flat, red areas which became ‘bumpy’ and then developed into
palpable dark red–purple lumps that failed to blanch on pressure. The abdominal pain occurs in spasms and does not appear
to relate to food. His bowel habit is unchanged.
Examination
This youth is well but clearly very uncomfortable. His pulse rate is 84/min and blood pressure 117/62 mmHg. He has
palpable purpura over his buttocks and the backs of his legs. His right ankle is mildly synovitic but otherwise his joints are
normal and he has no other stigmata of inflammatory disease. Palpation of his abdomen reveals diffuse tenderness but no
guarding or rebound. There is no organomegaly and normal bowel sounds are audible.
Buerger disease is also known as Henoch–Schönlein purpura (HSP) and IgA nephropathy
Purpura are the result of a spontaneous extravasation of blood from the capillaries into the skin. If small they are known as
petechiae, when they are large they are termed ecchymoses.
The combination of palpable purpura, abdominal pain, arthritis and renal disease is a classic presentation of Henoch–Schönlein
purpura (HSP).
HSP is frequently self-limiting small-vessel vasculitis that can affect any age; but the majority of cases present in children aged
2–10 years.
Differential diagnosis for purpura include:
a. Infection; meningococcal disease, infective endocarditis, septicaemia
b. Thrombocytopenia; idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura
c. Vascular defect; senile or steroid-induced purpura, vasculitis
d. Coagulation defect; hemophilia
e. Drugs; steroids, sulphonamides
Signs and symptoms:
1. Petechiae
2. Abdominal pain
3. Renal involvement characterized by proteinuria and microscopic hematuria (glomerulonephritis)
4. Arthritis
Diagnosis:
1. Urinalysis and urine dipstick for renal function
2. Skin biopsy ( leukocytoclastic vasculitis with IgA deposition in the affected blood vessels)
3. Kidney biopsy shows IgA deposition in glomeruli
Treatment:
1. mild cases do not require a specific therapy
2. For arthritis; NSAIDs, steroid therapy
3. High-dose steroids and cytotoxics such as cyclophosphamide for renal disease
4. Plasma exchange or intravenous immunoglobulin for refractory cases
Behçet syndrome
History
A 26-year-old Turkish man presents to his general practitioner with a painful aphthous ulcer on his scrotum. Although he has
had oral ulcers on and off ‘for years’, this is the first episode in the genitourinary tract. He denies other genitourinary
symptoms and is not sexually active. Four weeks previously he experienced a rash over the front of his shins: discrete red
Muran Mjahed 42
tender lumps appeared and then faded spontaneously, going through color changes like a bruise. On systems review he
mentions that his right knee is intermittently painful and swollen, but denies any other problems.
Examination
This young man has a deep ulcer on his scrotum, but his penis is normal. He has no oral ulcers. The sclera of his right eye is
injected. He has a solitary brown slightly raised lesion on his left shin and a small effusion in the right knee. He has an
erythematous lesion in the left antecubital fossa from blood donation 48 hours previously
An autoimmune, multisystem vasculitic disease; cause is unknown.
Both genders are affected equally but males develop more severe disease.
Associated with HLA B51- MHC class 1
Often present in Middle Easterners, mediterranean and turkish individuals
Signs and symptoms:
1. Painful, sterile oral and genital ulcerations (pathergy)
2. Arthritis (knees and ankles most common)
3. Eye involvement (uveitis, optic neuritis, iritis, conjunctivitis)
4. CNS involvement (meningoencephalitis, intracranial HTN)
5. Fever
6. Weight loss
7. Erythema nodosum and cutaneous manifestations
8. Pathologic lesions are systemic perivasculitis with early neutrophil infiltration and endothelial swelling
Pathogenesis:
Activated neutrophils with ↑Th1, Th17, cytotoxic CD8 and γ T cells
Diagnosis:
1. biopsy of involved tissue (inflammation and necrosis)
2. Antibodies against:
- Alpha enolase (endothelial cells)
- Selenium binding proteins
- Anti saccharomyces cerevisiae
3. No specific diagnostic test or laboratory finding
Treatment:
1. Steroids for severe disease
2. Tacrolimus
3. Mucocutaneous disease can be treated with colchicine, dapsone or thalidomide
4. Cyclophosphamide is generally reserved for life- or sight-threatening disease
Differential diagnosis:
1. Sarcoidosis
2. Reactive arthritis
3. Vasculitis
4. Crohn's disease
5. Systemic lupus erythematosus
Rheumatic fever
History
A 16-year-old boy is referred to the medical team with abnormal involuntary facial movements. He was well until 8 weeks
before admission when he developed a sore throat and febrile illness, associated with pain and swelling in several large joints.
The symptoms began in his knees, before moving to his ankles and finally his elbows and responded only partially to
Muran Mjahed 43
ibuprofen. However, he made a full recovery within 3 weeks. For the last 24 hours his parents have noticed emotional lability
and involuntary rapid and purposeless movements, particularly in his face. He denies weakness or sensory loss.
Examination
This adolescent is well and not febrile. He has brief uncoordinated facial movements consistent with chorea. His skin, nails
and mucosal surfaces are normal. Cardiovascular examination reveals a friction rub and pansystolic murmur in the mitral area.
Respiratory and abdominal examinations are normal. There is a cool effusion in his left elbow.
Acute rheumatic fever is an immunologically mediated systemic process that may progress to rheumatic heart disease.
The arthritis associated with rheumatic fever is mild, nonerosive and self-limiting, tending to resolve within 2–4 weeks.
Signs and symptoms:
1. Arthritis of large joints (knees, ankles, elbows and wrists) in most patients
2. Fever
3. Chorea
4. polyarthritis
5. Subcutaneous nodules
Diagnosis of Acute Rheumatic Fever requires two major criteria or one major and two minor criteria
1.
Major criteria
a. Migratory polyarthritis
b. Erythema marginatum
c. Cardiac involvement (e.g., pericarditis, CHF, valve disease)
d. Chorea
e. Subcutaneous nodules
2.
Minor criteria
a. Fever
b. Elevated erythrocyte sedimentation rate
c. Polyarthralgias
d. Prior history of rheumatic fever
e. Prolonged PR interval
f. Evidence of preceding streptococcal infection
Diagnosis:
1. Echocardiogram (assess valvular insufficiency and to identify a pericardial effusion)
2. Based on Duckett Jones
3. Evidence of previous infection with GAS
4. elevated Antistreptolysin titre helps confirm the diagnosis
5. elevated ESR/CRP, a normocytic anemia, neutrophilia and hypoalbuminemia
Treatment:
1. Treatment of GAS with penicillin; if resistant, treat with macrolides or cephalosporins
2. Give NSAIDs
Prophylaxis with penicillin should be continued for 5 years or until 21 years of age, whichever is longer.
Sarcoidosis
History
A 28-year-old African-American man presents to the rheumatology department with a 2-week history of painful swollen
ankles and a rash over his shins. His rash is fluctuating with crops of raised tender lumps that fade spontaneously. His ankle
pain initially responded to a non-steroidal anti-inflammatory drug (NSAID), but over the last few days has deteriorated such
that he finds it hard to walk. His medical history is unremarkable, except for an acutely painful red eye several months
Muran Mjahed 44
previously for which he saw an ophthalmologist and was given steroid eye-drops. He cannot recall the diagnosis he was given
at the time. Systems review is unremarkable.
Examination
This man has synovitis affecting both ankles, with a mild effusion on the left and lesions suggestive of resolving erythema
nodosum over his shins
A chronic systemic granulomatous disease characterized by noncaseating granulomas, often involving
multiple organ systems. Lungs are almost always involved. Etiology unknown.
Occurs most often in the African American population, especially women
Caused by exposure to smoking, amiodarone use…
Signs and symptoms:
1. Constitutional symptoms; malaise, fever, anorexia, weight loss
2. Lungs: dry cough, dyspnea (especially with exercise), chest pain
3. Skin; erythema nodosum, plaques, subcutaneous nodules, maculopapular eruptions
4. Eyes; visual impairment, anterior uveitis, posterior uveitis, conjunctivitis
5. Heart; arrhythmias, conduction disturbances, such as heart block Sudden death
6. Musculoskeletal system; arthralgias and arthritis and bone lesions
7. Nervous system; Cranial nerve VII involvement (Bell palsy), optic nerve dysfunction, papilledema, peripheral
neuropathy
Pathogenesis:
Stages of sarcoidosis:
a. Stage 0: Normal
b. Stage 1: Bilateral hilar lymphadenopathy
c. Stage 2: Bilateral hilar lymphadenopathy and pulmonary infiltrates
d. Stage 3: Pulmonary infiltrates and restrictive lung disease.
Diagnosis:
1. Chest X-ray (Bilateral hilar adenopathy)
2. Skin anergy with tuberculin skin test
3. Angiotensin-converting enzyme (ACE) is elevated; secreted from the lungs
4. Hypercalciuria and hypercalcemia
5. transbronchial biopsy (noncaseating granulomas)
Treatment:
1. NSAIDs
2. Low dose corticosteroids; high doses are required in the presence of arthritis
3. Intra-articular injection of steroid may abort an acute attack
4. Immunosuppression such as cyclophosphamide is reserved for neurological or life-threatening disease