Connective Tissue Disorders Immune Disorders PT 635 Spring 2013 Lonnemann

I. Connective Tissue Disorders RA- Rheumatoid Arthritis SLE- Systemic Lupus Erythematosus Scleroderma Polymyositis & Dermatomyositis Polymyalgia Rheumatica Sjögren's syndrome Temporal Arteritis Mixed Connective Tissue Disease

Systemic Lupus Erythematosus A chronic inflammatory disease which affects multiple systems and is of autoimmune origin.

Patient Case-SLE Patient is a 33 year old female elementary school teacher who was referred to you by a rheumatologist with above diagnosis for evaluate and treat. Prevalence –20/100,000 in US –Female to male 9:1

PMH not significant Present Medical History: Recent diagnosis of SLE & Raynaud’s Associated Comorbidities –RA –SICCA (Sjögren’s) –Myositis –Scleroderma –Raynaud’s Medications: Plaquenil and Prednisone Antimalarials -- These agents are an alternative conservative therapy with both sunblocking and anti- inflammatory effects.

Lab Values Hemolytic Anemia- antibodies against RBCs Leukopenia –low white count CBC –Thrombocytopenia-low platelet count ERS Antinuclear antibody screen (ANA)-abnormal titer of anti-nuclear antibody PyuriaProteinuria

Causes-SLE Unknown –Role of Viruses –Genetic Abnormalities –Environmental-sun exposure –Hormonal –Immune complex formation

Systemic Lupus Erythematosus LE-001.html LE-001.html LE-002.html LE-002.html

Characteristics of Disease Pathology –Histological changes within the body occur as a result of immunologic attack associated with deposits of immune complexes within various tissues of the body.

Systemic Involvement-SLE I I. Integumentary System Butterfly Blush after exposure to sunlight May extend to exposed arms and chest Macropapular lesions sometimes present II. Musculoskeletal System Arthralgia-severe joint pain with no objective findings other than tenderness. Morning stiffness is common. Swollen tender joints Jacoud’s arthropathy

Systemic Involvement-SLE III. Cardiopulmonary/Cardiovascular – –Inflammatory changes in the pericardial and pleural membrane may cause Pleurisy Acute pericarditis Acute pneumonitis – –HTN – –Vasculitis as a result of immune complex deposits in the walls of the small arteries and capillaries Small vessels-purpura Large vessels-papular lesions Arterial thrombosis

Systemic Involvement-SLE IV. Gastrointestinal Ulcers-mouth and throat Peritonitis Pancreatitis Vasculitis of the vessels to the Small Intestine or Large Intestine

Systemic Involvement-SLE V. Kidney Glomerulonephritis- inflammatory disease of the kidneys VI. CNS Depression, ischemic episodes, peripheral neuropathy or seizures

Diagnostic Criteria >4 present = SLE Malar rash Discoid rash Photosensitivity Oral ulcers ArthritisSerositis Renal disorders Neurologic disorder Hematologic disorder Immunologic disorder Antinuclear antibody American College of Rheumatology ions/classification/SLE/sle.asp?aud= mem ions/classification/SLE/sle.asp?aud= mem

Evidence for Treatment –Medication Use –Corticosteroids depending on severity of disease

Recommendations for PT Management of SLE Patient Education – –Disease fluctuates and will enter periods of remission during which the patient will be symptom free NSAIDs may be adequate to control the symptoms in joints in milder cases PT for strength and range of motion Protection from the sun Compliance with medications and follow-up appointments patient education article Lupus (Systemic Lupus Erythematosus).Lupus (Systemic Lupus Erythematosus)

I. Connective Tissue Disorders RA- Rheumatoid Arthritis SLE- Systemic Lupus Erythematosus Scleroderma Polymyositis & Dermatomyositis Polymyalgia Rheumatica Sjögren's syndrome Temporal Arteritis Mixed Connective Tissue Disease

Scleroderma Systemic sclerosis Progressive systemic sclerosis CREST syndrome –Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly,Telangiectasias Telangiectasias Morphea –localized scleroderma affecting the skin

Scleroderma Multi-system condition or generalized disorder of collagen – –Musculoskeletal System – –Integumentary System – –GI System – –Cardiopulmonary – –Renal system Chronic and usually progressive disorder Pathology – –Gradually spreading fibrosis in the skin, synovium, muscles, and GI tract.

Scleroderma Prevalence – –20 cases per 1 million – –Female to male 3:1 – –Age of onset Associated Comorbidities – –Sjögren's syndrome – –Myositis – –Autoimmunity – –Mixed CT Disease

Causes In most cases the cause is unknown but often times it is associated with autoimmunity – – the immune system produces autoantibodies to an endogenous antigen, in this case collagen antibodies with consequent injury to collagenous tissues Viral infections have been suggested as a cause In rare cases – –Silica dusts (mines) – –Polyvinyl or vinyl chlorides – –Hydrocarbons –Chemotherapy Canola/Rapeseed UofC

Systemic Involvement- Scleroderma Characteristics of Disease Gradual onset I. Integumentary: tissue fibrosis causing skin thickening and induration – – Raynauds Phenomenon- small blood vessel vasculopathy. Usually first complaint… – – Thickening of the skin of face causing puckering around the mouth and difficulty opening the mouth and chewing – – Calcinosis-calcium deposits around joints of the hand GroupID=79&groupIndex=0&numcols=0

Systemic Involvement-Scleroderma II. II.Musculoskeletal Collagen deposits in the synovial lining-joint pain, in tendon sheaths Often begins as joint pain in 15% of patients. In 10% of patients it begins as inflammatory myopathy Muscle weakness particularly hips and shoulders present in 80% of patients.   Associated myositis Joint pain, limitation of motion, contractures-flexion Progression from distal to proximal ↓ ↓Hands-swollen & stiff ↓ ↓ Distal Phalanges ↓ ↓Elbow ↓ ↓Trunk ↓ ↓Face

Systemic Involvement- Scleroderma III. Gastrointestinal – –Esophageal Dysfunction: Impaired contraction of the lower esophageal muscles – –Esophageal reflux/heartburn – –Dysphagia – –Symptoms of GI Dysmotility Vomiting, Nausea, Weight Loss

Systemic Involvement- Scleroderma IV. IV.Cardiopulmonary – – DOE – – Pulmonary infiltrates V. V.Renal – – Severe cases affects arterioles to the kidney resulting in renal hypertension

CREST C = Calcinosis R = Raynaud's E = Esophageal dysmotility S = Sclerodactyly T = Telangiectasias More benign course of scleroderma

Evidence for Treatment Primarily medical relative to Raynaud’s No evidence for other therapies – –Cochrane Review 98 Issue 2 Level A – –Prazosin, Iloprost and Cisaprost for Raynaud’s Phenomenon in Sytemic Sclerosis Level B – –Methotrexate and CA+ Channel Blockers

Recommendations for Management of Scleroderma PT – –Early stages Active and Passive exercise s/bradenstein_1999.shtm Patient Education –cold exposure, joint preservation OT – –Joint preservation principles – –Devices for independent living

I. Connective Tissue Disorders RA- Rheumatoid Arthritis SLE- Systemic Lupus Erythematosus Scleroderma Polymyositis & Dermatomyositis Polymyalgia Rheumatica Sjögren's syndrome Temporal Arteritis Mixed Connective Tissue Disease

Polymyositis & Dermatomyositis Idiopathic Inflammatory diseases of Skeletal Muscle (myopathies) Prevalence – –8/100,000 – –Female to male 9:1 Associated Comorbidities – –CA in elderly

Characteristics of Disease Clinical Features – –Gradual onset In both Polymyositis and Dermatomyositis – – Symmetrical Proximal Muscle weakness affecting shoulder and pelvic girdle – –In severe cases patient may be unable to rise from supine

Dermatomyositis Facial Rash-deep red with Gottron’s papules (small flat topped papules-IP joints) Diffuse scale in scalp and facial regions, but with involvement also in IP or MCP’s Pulmonary, nonproductive cough, rales, sometimes respiratory failure Pharyngeal : dysphagia, dysphonia Carrino, J. Advances in Musculoskeletal Imaging:Rheumatology. The John Hopkins Arthritis Center. Available at: arthritis.org. arthritis.orgwww.hopkins- arthritis.org

Gottron papules located over the interphalangeal and metacarpophalangeal joints. Cleland J A, Venzke J W PHYS THER 2003;83: ©2003 by American Physical Therapy Association Dermatomyositis: Evolution of a Diagnosis

Polymyositis & Dermatomyositis Pathology – –Inflammatory infiltrates in muscle fibers causing muscle fiber degeneration and necrosis. – –Dermal edema, calcification and epidermal atrophy are present in dermatomyositis

File photo of heliotrope discoloration of the eyelids and macular erythema of the face and forehead. Cleland J A, Venzke J W PHYS THER 2003;83: ©2003 by American Physical Therapy Association

Polymyositis & Dermatomyositis

Laboratory Values Elevated enzymes associated with muscle – –Transaminases – –Creatine Kinase – –Lactate dehyrogenase EMG Testing—inflammatory myopathies (short-duration, low-amplitude, polyphasic potentials), positive sharp waves, fibrillations

Evidence for Treatment Corticosteroids-usually successful

Recommendations for PT Management of Polymyositis & Dermatomyositis Patient Education PT for strengthening to tolerance and range of motion

I. Connective Tissue Disorders RA- Rheumatoid Arthritis SLE- Systemic Lupus Erythematosus Scleroderma Polymyositis & Dermatomyositis Polymyalgia Rheumatica Sjögren's syndrome Temporal Arteritis Wegener’s Granulomatosis Mixed Connective Tissue Disease

Polymyalgia Rheumatica Cause: Unclear Pathology: Subclinical synovitis of the shoulder and pelvic joints

Clinical Features-PMR – –Pain-muscle and joint with motion – –Very specific time of onset to the day and hour – –<60 years of age

Lab Values-PMR – –ESR is elevated to the same level as the patients age – –Muscle biopsies are negative – –Mild elevation of liver enzymes – –Normal muscle enzymes

Clinical Management of PMR Diagnosis and Intervention – –Dramatic/overnight response to low dose corticosteroids Associated Comorbidities – –Temporal Arteritis 10%

I. Connective Tissue Disorders RA- Rheumatoid Arthritis SLE- Systemic Lupus Erythematosus Scleroderma Polymyositis & Dermatomyositis Polymyalgia Rheumatica Sjögren's syndrome Temporal Arteritis Wegener’s Granulomatosis Mixed Connective Tissue Disease RA- Rheumatoid Arthritis SLE- Systemic Lupus Erythematosus Scleroderma Polymyositis & Dermatomyositis Polymyalgia Rheumatica Sjögren's syndrome Temporal Arteritis Wegener’s Granulomatosis Mixed Connective Tissue Disease

Temporal Arteritis >50 years, F>M 5:1 Pathology: – –Chronic inflammatory change found in the arteries arising from the external carotid circulation Clinical Features – –Unilateral throbbing pain in the temporal area – –Tenderness to palpation of the temporal artery – –Pain on chewing

Temporal Arteritis Diagnosis – –Lab values Elevated ESR – –Temporal artery biopsy- multinucleated giant cells hence giant cell arteritis Clinical Management – –Immediate Referral to Physician – –If untreated can lead to blindness, or stroke – –Loss of vision due to narrowing of the opthalmic arteries – –Treatment with corticosteroids-Prednisone Opthalmic Branch of External Carotid

Mixed Connective Tissue Disease Overlap of symptoms similar to SLE, myositis and scleroderma Cause is unknown, autoimmune in nature Pathology – –B lymphocyte hyperactivity--high levels of RNP autoantibodies –required for diagnosis

Immune System Disorders Immune System Disorders Organ Specific –Addison's disease –Crohn's disease –Chronic active hepatitis –Diabetes mellitus –Giant cell arteritis –Hemolytic anemia –Idiopathic thrombocytopenic purpura –Polymyositis/dermatomyositis –Postviral encephalomyelitis –Primary biliary cirrhosis –Thyroiditis Graves' disease Hashimoto's disease –Ulcerative colitis Systemic –Amyloidosis –Ankylosing spondylitis –Mixed connective tissue disease –Multiple sclerosis –Myasthenia gravis –Polymyalgia rheumatica –Progressive systemic sclerosis (scleroderma) –Psoriasis (psoriatic arthritis) –Reiter syndrome –Rheumatoid arthritis –Sarcoidosis –Sjögren's syndrome –Systemic lupus erythematosus