Connective Tissue Disease, Vasculitis, and Related Disorders Lecture Notes PDF

Connective Tissue Disease, Vasculitis and Related Disorders By: Salsabiela Bani Hamad Connective tissue disease: Connective tissue includes: 1- Extracelluler matrix 2- Support proteins ( collagen, elastin ) Connective tissue disease can be difficult to define but encompasses disorders that involve t...

Connective Tissue Disease, Vasculitis and Related Disorders By: Salsabiela Bani Hamad Connective tissue disease: Connective tissue includes: 1- Extracelluler matrix 2- Support proteins ( collagen, elastin ) Connective tissue disease can be difficult to define but encompasses disorders that involve the tissues connecting and surrounding organs. Connective tissue disease Mechanism: Autoimmune disease is caused by dysregulation of the immune system in a patient with a genetic susceptibility after being exposed to a trigger. This immune dysregulation leads to inflammation then signs and symptoms develop. Triggering factors: 1- Unknown (usually) 2- Sunlight 3- Infection 4- medication In autoimmune disorders, immune cells may be attracted to: 1- Particular target within the skin locally (pemphigus, pemphigoid). 2-Accumulate at sites of connective tissues in multiple organs (SLE, dermatomyositis) Diagnosis: Hx taking and Physical Examination: Cutaneous lesions (esp face and finger) Joints pains Muscle aches Malaise Weakness Photosensitivity Raynaud’s phenomenon Alopecia Vasculitis: Complex reactions occurring specifically in the capillaries and arterioles of the skin may lead to cutaneous erythema. Pathophysiology : - Complex and poorly characterized. - Antibodies or immune complex-mediated. - Immune complex deposition at blood vessel wall >> Inflammation >> Complement activation & inflammatory mediators release >> vasodilatation & polymorph accumulation >> Leakage so RBC extravasation >> occlusion of blood vessels >> Ischemia. Vasculitis: Clinical Presentation: General malaise Fever Abdominal pain Arthropathy Skin lesions: - Non-blanching Erythematous macular, palpable purpura Can become blistering, ulcerated, and necrotic. Transient or last for weeks. Painful and unpleasant. M.c Location: Lower Limbs Bullous vasculitis with necrosis Vasculitis: Underlying Etiologies: (imp) 1. Infection 2. Medication 3. Connective tissue disorder 4. Underlying malignancy 5. Vascular/ coagulopathy disorder 6. Inflammatory Bowel Diseases 7. Sarcoidosis 8. Behcet’s syndrome 9. Endocarditis 10. Hepatitis 11. Kawasaki Disease Diagnosis: 1. History 2. Physical Examination 3. Skin biopsy for histology and immunofluorescence (helpful but usually not diagnostic of the underlying cause. Polyarteritis Nodosa (PAN) PAN is a systemic vasculitis of small to medium-sized arterioles. The most common affected site is blood vessel bifurcation. Most commonly affects the skin and joints. ANCA may be +ve Polyarteritis Nodosa Clinical Presentation: Retiform Purpura General: General malaise Fever Weight loss Weakness Arthralgia Neuropathies Renal involvement (can cause renal failure) Cutaneous: Livedo reticularis (subtle lacy mottled pattern) Purpura Tender subcutaneous nodule Ulceration Necrosis M.C location: Lower limbs. Livedo reticularis Retiform Purpura Polyarteritis Nodosa Retiform Purpura Ulceration Necrosis Polyarteritis Nodosa (PAN) Investigations: 1. Angiography 2. Tissue biopsy ( skin, sural nerve, muscle ) Management: 1. Corticosteroids (oral) 2. Might add Cyclophosphamide in severe cases. Henoch – Schönlein purpura Occurs in children (75%) or young adults. M>F Unknown etiology but 50% have preceding URTI symptoms and +ve antistreptolysin O titer (ASOT) Pathophysiology: Deposition of IgA, complement and immune complexes in small vessels (arterioles, capillaries , venules) leading to systemic vasculitis. Skin, kidney, GI tract, and joints are mainly affected. Henoch – Schönlein purpura Clinical Presentation: Cutaneous: Vasculitic rash on the buttocks and lower legs Might be associated with edema of scrotum/hands/ears GI: Abdominal pain, Vomiting Joint pains in the knees/ankles Hematuria. Henoch – Schönlein purpura Henoch – Schönlein purpura Investigations: 1. Hx and P/E 2. Skin biopsy:  Deposition of IgA on immunofluorescence (support the diagnosis). Management : Usually supportive (recovery in weeks) Systemic corticosteroids:  If persistent disease  Can treat skin, GI, and arthritis symptoms  Don’t prevent or treat renal disease Management of cutaneous vasculitis Treat any underlying causes. Support hosiery should be used and the leg elevated on sitting. For mild to moderate cutaneous involvement: Potent topical steroids can be applied to the affected skin. In severe cases: Systemic corticosteroid Anticoagulation with warfarin or heparin. In persistent cases: Alternative immunosuppressants (Methotrexate or Azathioprine) may be needed. Raynaud’s phenomenon Recurrent reversible vasospasm of peripheral arterioles secondary to cold exposure leads to transient ischemia of the digits Can be associated with an underlying autoimmune disease (called Raynaud’s disease) Most commonly associated with systemic sclerosis, mixed connective tissue disease, SLE, and Cryoglobulinemia. Types: 1. Primary: Symmetric, before 30 years old, no skin manifestations, idiopathic. 2. Secondary: Asymmetric, ANA can be +ve, digital ulcerations can occur. Raynaud’s phenomenon: Symptoms: 1- Change in color after cold exposure:  White (Vasospasm) >> Blue (Cyanosis) >> Red (hyperemia). 2- Pain 3- Numbness The condition most frequently affects the finger in a symmetrical pattern Can also affect toes, nose, and ears. Raynaud’s phenomenon: Investigations: 1- Full blood count 2- LFT and KFT 3- Coagulation profile 4- Thyroid function 5- Serum glucose 6- Creatinine kinase 7- Hepatitis serology 8- Antinuclear antibodies Management : 1- Keeping peripheries warm 2- Nifedipine 3- Iloprost (Prostacycline Analogue) Systemic sclerosis (SSc) Excessive sclerosis (i.e. collagen deposition and fibrosis) of the subcutaneous tissues in the fingers and toes as well as around the mouth (scleroderma), with similar changes affecting the internal organs, particularly the lung and kidneys. Blood vessels can be affected, leading to:  Raynaud’s phenomenon (fingers)  Telangiectasia (mouth and fingers) Systemic sclerosis (SSc) classification: Main: 1- Limited systemic sclerosis(lSSc): Raynaud starts many years before Anti-centromere antibody Skin sclerosis distally does not cross the elbows and knees Slowly progressing CREST is an example 2- Disseminated systemic sclerosis (dSSc): Raynaud starts 1-2 years before Antibodies ANA, Scl-70 (anti topoisomerase) Sclerosis crosses elbows and knees Fast progress with internal organs involvement ( heart, kidneys, lungs) other 1- Undifferentiated connective tissue disease 2- CREST syndrome. Systemic sclerosis (SSc) Clinical Features: 1- Raynaud’s phenomenon 2- Telangiectasia (mouth and finger ) 3- Tethering of skin on the fingers/toes which become very tight with a waxy appearance and considerable limitation of movement. Systemic sclerosis (SSc): Diagnosis: 1- ANA ( 90% of patients with SSc will have at least one +ve ANA) 2- CRP / ESR ( raised) 3- High-resolution CT scan of the lung (thickening of the alveolar walls) 4- PFT (impaired ventilation – perfusion) 5- Skin biopsy (fibrotic changes seen in histology ) Systemic sclerosis (SSc) Morphaea : - Benign form of localized systemic sclerosis in which there is localized sclerosis with very slight inflammation. - Early stages: Dusky appearance of skin. - Late stages: Discolored and Firm skin. - Localized morphea in the frontoparietal area is associated with alopecia and sunken groove of firm sclerotic skin. CREST syndrome: Symptoms: Calcinosis Cutis: Calcium deposits in the skin are seen as chalky white material which can be painful Raynaud’s phenomenon: First complaint Esophageal Dysmotility Sclerodactyly: Thickening of the skin of the digit Telangiectasia: first seen in the face CREST syndrome: Investigations: FBC (Full Blood Count) ANA Anticentromere antibodies Scl-70 Management: (multidisciplinary) Psychological support Patients should keep themselves warm Calcium-channel blockers Prostaglandins/prostacyclin analogue. Calcitriol (for sclerodactyly) Pulsed dye laser (for telangiectasia) Lichen Sclerosus: Itchy eruption which mainly affects the genital and perineal regions in women. Pathophysiology: Unknown, but in early lesions there is an infiltrate of lymphocytes with CD3, CD4, CD8, and CD68 markers. Histologically: There are some similarities between LS and lichen planus but with different clinical pictures. Lichen Sclerosus: Clinical Features: Well-demarcated atrophic patches and plaques with a distinctive ivory-white color. Fibrosis of the underlying tissues with associated loss of normal genital architecture Frequently affects the vulva and perineum, but may also affect the penis and extragenital skin. Children: Acute, resolves Adults: chronic, rarely associated with the development of squamous cell carcinoma (SCC). Lichen Sclerosus: Treatment: Intermittent potent topical steroids, which usually control itching. If pruritus is not controlled by potent topical steroids or soreness develops, you have to rule out the development of SCC. Lichen Planus: Etiology unknown, immune-mediated Histological features: Characterized by a band of lymphocytes attacking the basal keratinocytes which result in edema, subepidermal clefts, and death of some keratinocytes Lichen Planus: Clinical features: Itchy eruption consisting of shiny purplecolored flat-topped papules (6 Ps: Pruritic polygonal purple planar papules and plaques) Appear on the wrists and ankles. White lines called Wickham’s striae may appear on the surface of the lesions at any site Lesions may appear in clusters or in linear scratches/surgical scars (Koebner phenomenon) Lichen Planus: Clinical features: In patients with black skin, LP may be very hypertrophic and heal with marked post-inflammatory hyperpigmentation. Mouth (buccal mucosa), and genitals (erosions on labia minora ) may also be involved Distinctive linear ridges may affect the nails. Scalp lesions are often scaly with marked follicular plugging that may result in scarring alopecia. Prognosis: Most cases resolve over 1–2 years. Hypertrophic LP may, however, persist for decades. Lichen Planus: Clinical features: Severe acute lichen planus can manifest as bullous lesions Treatment : Potent topical steroid applied to the itchy active lesions Occlusion of the steroid for hypertrophic lesions. Severe lichen planus can be treated with systemic Corticosteroids, mycophenolate mofetil, methotrexate, or azathioprine Lichenoid drug eruptions: Clinical Features: Clinically similar to LP Lesions are usually more extensive and oral involvement is rare. Lesions only resolve very slowly after the drug is stopped, generally taking 1–4 months to settle and usually leaving hyperpigmentation on the skin. Culprit Medications: Antihypertensives, ACE inhibitors, beta-blockers, nifedipine, methyldopa Lupus erythematosus (LE) It is an autoimmune disorder characterized by the presence of antibodies against various components of the cell nucleus. Clinical variants of lupus erythematosus Systemic (SLE) Subacute cutaneous lupus Discoid Lupus Neonatal Lupus Systemic Lupus erythematosus (SLE) SLE is a multi-systemic disease. 75% of patients have skin involvement, most commonly an erythematous ‘butterfly’ distribution rash on the face, Photosensitivity, hair loss, and areas of cutaneous vasculitis. As the disease progresses the cutaneous manifestations can become extensive. Systemic changes include fever, arthritis, and renal involvement, but there may be involvement of a wide range of organs. Butterfly rash Extensive severe SLE Systemic Lupus Erythematosus (SLE):  SLE has been triggered by drugs including chlorpromazine, quinine, and isoniazid.  Diagnostic criteria for SLE include four of the following at any given time: Malar rash Serositis Discoid plaques Neurological disorders Photosensitivity Hematological changes Arthritis Immunological changes Mouth ulcers Antinuclear antibodies Renal changes. New Criteria for SLE: Systemic Lupus erythematosus (SLE) Treatment of SLE with threatened or actual involvement of organs is important. Prednisolone is usually required Sometimes immunosuppressant drugs such as azathioprine as well. Subacute lupus erythematosus (SLE) Erythematous annular and serpiginous eruption on the skin Systemic involvement is less common/severe than in SLE. High incidence of neonatal lupus erythematosus in children born to mothers with the condition. E.N.A (extractable nuclear antigen) test is positive in 60% and anti-cytoplasmic antibodies are present in 80% of patients. Discoid lupus erythematosus (DLE) Photosensitive disorder Circulating antinuclear antibodies are very rare Only 5% of patients go on to develop SLE Clinical Features: Well-defined erythematous lesions with atrophy, scaling, and scarring occur on the face, scalp (alopecia, follicular plugging), and occasionally arms. Treatment: Potent and super-potent topical steroids to limit scarring Hydroxychloroquine 200mg twice daily can be effective (ask about eye sx, rare ocular toxicity) Neonatal lupus erythematosus Caused by transplacental passage of maternal lupus antibodies (particularly Ro/La) to the neonate. Clinical Features: Skin lesions characterized by annular scaly and inflammatory lesions on the face/scalp. Congenital heart block (which may require pacing). Treatment: Skin lesions may require topical steroids and sunscreen but usually resolve spontaneously as the level of autoantibody depletes. Dermatomyositis: A rare disorder that affects the skin, muscles, and blood vessels. In adults may precede the diagnosis of an underlying tumor (most commonly breast, lung, ovary, or gastrointestinal tract) Clinical Features: Rash on a photosensitive distribution. Characterized by a purple hue (heliotrope) on the upper eyelids, cheeks, and forehead. The anterior neck and chest rash is a ‘V’ sign while posteriorly is called a shawl sign. ‘V’ sign Shawl sign Heliotrope Rash Dermatomyositis: Clinical Features: The dorsal surface of the fingers may be affected by the erythematous eruption and purplish (Gottron’s) papules may predominate over the dorsal finger joints. Gottron’s papules Ragged cuticles and dilated nail-fold capillaries may also be seen. There is a variable association with muscle discomfort and weakness, which is mainly in the proximal limbs but bulbar and respiratory muscles may be affected. Ragged cuticles and dilated nail-fold capillaries Dermatomyositis: Investigations: Labs: Creatine phosphokinase (CK), ESR, Anti-Jo-1 antibody. Skin and muscle biopsy. Electromyography and MRI can help demonstrate myositis. Treatment: High-dose systemic corticosteroids (60–100mg daily) or pulsed methylprednisolone (1 g daily for 3 days) helps achieve rapid control of symptoms. Pulsed cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil. Treatment of any underlying malignancy will usually lead to the resolution of these skin signs. Mixed connective tissue disease (MCTD) Overlapping features of SLE, scleroderma, and myositis with characteristic autoantibodies. Clinical Features: They usually have Raynaud’s phenomenon, sclerodactyly/swollen hands, arthritis/ arthralgia, Sjogren syndrome, myositis, malaise, oesophageal dysmotility, trigeminal neuralgia, & pulmonary hypertension. Investigations: Positive antibodies to U1-ribonucleoprotein (RNP) and small nuclear ribonucleoprotein (snRNP) Treatment: NSAIDs are used to reduce pain and inflammation and the newer cyclooxygenase 2 (COX-2) inhibitor celecoxib is increasingly used to help reduced arthritis and myositis. Hydroxychloroquine For refractory disease low dose of oral corticosteroids and methotrexate Thank You