Classification of Vasculitis and Leukocytoclastic Vasculitis PDF

**CLASSIFICATION OF VASCULITIS AND LEUKOCYTOCLASTIC VASCULITIS** Moderator: Dr. Priya K. S Presenter: Dr. P Akhila **Introduction:** Vasculitis represents a specific pattern of inflammation, involving a blood vessel. The term 'cutaneous vasculitis' refers to vasculitis with any underlying etiolo...

**CLASSIFICATION OF VASCULITIS AND LEUKOCYTOCLASTIC VASCULITIS** Moderator: Dr. Priya K. S Presenter: Dr. P Akhila **Introduction:** Vasculitis represents a specific pattern of inflammation, involving a blood vessel. The term 'cutaneous vasculitis' refers to vasculitis with any underlying etiology or affecting any sized vessels but having cutaneous findings. **Leucocytoclastic Vasculitis:** **Synonyms:** Cutaneous small vessel vasculitis, Hypersensitivity angiitis, Cutaneous necrotizing venulitis. **Introduction:** It is a vasculitic process that involves primarily the dermal post capillary venules and small arterioles. The term leukocytoclastic vasculitis (LCV) refers to histopathologic description of small vessel vasculitis. **Epidemiology:** Incidence is 15 per million. Affects all age groups but more common (90%) in adults. Both genders may be affected, with a mild female predominance.  **Etiology of CSSV:** - **Idiopathic- 45-55%** - **Drugs (10-15%)** +-----------------------+-----------------------+-----------------------+ | **Cardiovascular** | **Antibiotics:** | **Others:** | | | | | | Thiazides. | Esp, β Lactams. | NSAIDS. | | | | | | Hydralazine | Pencillins. | Allopurinol. | | | | | | | Cephalosporins. | Propyl Thiouracil. | | | | | | | Quinolones. | | | | | | | | Macrolides. | | +-----------------------+-----------------------+-----------------------+ - **Infections (15-20%)** - **Inflammatory Disorders, (15-20%)** Rheumatoid arthritis. SLE. Sjogren syndrome. - **Neoplasms, (2-5%)** Multiple myeloma, Plasma cell dyscrasias. Hairy cell leukaemia. Myelodysplasia **Histopathology of LCV:** It is characterised by: - Neutrophilic infiltration within and around the vessel wall. - Signs of leukocytoclasics: Degranulation and fragmentation of neutrophils leading to production of nuclear dust. - Fibrinoid necrosis (fibrin deposition within and around vessel walls). - Signs of damage of vessel wall and surrounding  **Pathogenesis:** It is mediated by immune complex deposition.  **Clinical Features:** The American college of Rheumatology has produced classification criteria for CSSV.  **Symptoms:** - Cutaneous lesions of CSSV are mostly asymptomatic. - Itching, burning or pain may be present. - Associated symptoms of fever, arthralgia, myalgia should be asked. - History of new medications, dosage of existing medications, IV drug use, transfusions, travel history to be noted. - Complete review of symptoms to rule out other systemic vasculitides. **SYSTEMIC MANIFESTATIONS TO LOOK FOR SYSTEMIC VASCULITIDES** **Signs:** **Palpable purpura**: Refers to raised (palpable) lesions red to purple in colour, ranging from 2-5 mm in size.  - The raised appearance as well as erythema are attributable to the inflammatory response in the skin. - Prominent involvement of lower limbs, dependant sites with fewer lesions on proximal sites. **Why does small vessel vasculitis favour the lower legs?** - Stasis: Gravity pooling and slowing blood flow in the lower limbs. - This leads to deposition of mediators of inflammation in blood vessel. - Prolonged standing exaggerates venous hyper tension and thus increases blood leakage in purpura. **Lesions occur on:** - Areas affected by trauma (Koebner phenomenon). - Under tight fitting clothes. - Walking or hiking in hot weather. - Lesions may also be like urticaria (edematous pink papules or plaques), resolving with dusky patches or may be targetoid in appearance. - Residual post inflammatory hyperpigmentation may persist for months **Prognosis:** - 90 percent of patients have spontaneous resolution of cutaneous lesions in several weeks. - 10 percent will have chronic or recurrent lesions. **Investigations:** **The laboratory evaluation of patients with CSVV can be sectioned into:** - Skin biopsy to confirm the diagnosis. - Evaluation for therapy and disease activity. - Evaluation to rule out other differentials. - Evaluation to rule out systemic involvement. **Skin biopsy**: - Punch biopsy (generally 4mm or longer) should be taken from the centre of fresh lesion, ideally with 24-48 hrs of onset. - Separate lesion is taken for direct immunofluorescence testing. - If infection is suspected, tissue may also be sent for bacterial, fungal and mycobacterial cultures. - Neutrophil infiltrate into post capillary venules. - Leukocytoclasis and fibroid necrosis.  **Direct Immunofluorescence test (DIF):** - Demonstration of deposits C3, IgM or IgG in a granular pattern within vessel wall (80% of CSSV cases). - Immunoglobin deposition is highest (100%) in skin lesions ≤ 48 hrs. - DIF will be negative and only C3 will be detected in lesions present for ≥ 72 hrs IgA positivity raises suspicion of Henoch -- Schoenlein purpura  **Evaluation of Disease activity and for therapy:** Inflammatory markers: - CRP, ESR may be raised. - CBC with differential count, blood sugar, RFT and LFT for therapy purposes. **Evaluation to rule out other differentials:** Anti-nuclear anti body (ANA). Rheumatoid factor. Anti-streptolysin- O. HBV, HBC serology. Montoux for T. HIV test. Antiphospholipid antibody. **Evaluation to rule out systemic evaluation:** Stool for occult blood. Chest X-ray, pulmonary function tests. Visceral angiography, ECHO to look for systemic vasculitides. Algorithm for diagnosis of cutaneous small vessel vasculiti **Treatment:** - Disease may be self-limiting. - Triggering agent if identified like infection or drug should be treated or removed. - Efforts to minimize stasis such as use of compression hosiery and elevation of dependant areas. - Use of anti-histamines or anti-inflammatory drugs may reduce symptoms. **Treatment of bullae or ulcers with short course of steroids.** Prednisolone: Initial dose of 0.5-1mg/kg is tapered over 6-weeks depending on response. **Recurrent episodes/ persistent and severe disease:** Colchicine: dose of 0.6mg bd orally. Dapsone: Initially 5mg/day and increased by 50mg/ day at weekly intervals until dose of 150-200mg is reached/ effect is achieved **Refractory to above therapies.** Cytotoxic agents: Azathioprine (1-2mg/kg per day), Methotrexate (15-25mg per week). **Schematic approach to the treatment of leukocytoclastic vasculitis.**  **Approach to vasculitis** Identify the vessel involved - In the large vessel, it is classified as Giant cell artirits and Takayasu disease. - In the medium vessel, it is classified as RAN and Kawasaki disease. - In the small vessel, Granulomatous is then classified into Wegener's granulomatous and Churg-strauss syndrome. - Whereas, Non-Granulomatous is classified as HP Purpura, Urticarial vasculity and LCV. **Small vessel Vasculitis (Immune complex vasculitis)** **Henoch- Schonlein purpura:** - It is an IgA mediated vasculitis involving small vessels of skin, GI tract, Skin, Kidney and joints. - Peak age: 4-6 years. - Classification: classic tetrad Palpable purpura, Abdominal pain, Haematuria, Arthritis. **INVESTIGATIONS:** **Skin Renal biopsy:** Leucoclastic vasculitis with IgA deposition. **Lab studies:** - Mild leucocytes. - IgA level elevated.  **Urticarial Vasculitis** - It is a variant of cutaneous small vessel vasculitis. - It is an eruption of erythematous wheals that clinically resemble urticaria but histologically show changes of LCV. C/F: Annular wheels lasting more than 24 hours. - Pain and burning sensation rather than itching. - Hyperpigmentation on resolution. - Systemic symptoms and signs. **Types:** - UV associated hypocomplementemia. - UV associated normo complementarian. **Investigations:** **Cryoglobulinemic Vasculitis:** It is an immune mediated small vessel vasculitis characterised by abnormal immunoglobulin proteins in the body. **Type 1:** Single monoclonal immunoglobulin, IgM. **Type 2:** Mixed cryoglobulinemia with monoclonal rheumatoid factor. **Type 3:** Mixed polyclonal RF.  **C/F: Meltzer's traid** - Purpura. - Arthralgia. - Weakness. **Small vessel vasculitis: (ANCA associated vasculitides):** Granulomatosis with polyangitis: Syn: Wegner's granulomatosis. **Classic Traid:** - Systemic small vessel vasculitis. - Necrotising granulomatous inflammation of both upper and lower respiratory tracts. - Glomerulonephritis. **Clinical Features:** **Cutaneous:** Palpable purpura, pyoderma granulosum ulcers, tender subcutaneous nodules. **Respiratory tract:** - Purulent sinus discharge, utitis media. - Saddle nose deformity. - Cavitary lesions in lung. **Renal:** Glomerulonephritis.  **Eosinophilic Glomerulonephritis with Polyangiitis:** **Syn:** Churg Strauss syndrome. It is a small vessel autoimmune vasculitis leading to necrosis. **C/F: Criteria for diagnosis: Presence of 4 or more criteria.** 1. H/o bronchial asthma. 2. Eosinophilia is greater than 10% of peripheral blood. 3. Paranasal sinusitis. 4. Pulmonary infiltrates. 5. Mononeuritis multiplex or poly neuropathy. 6. Histology: Vasculitis with extravascular eosinophils. **Investigations:** 1. Biopsy: 3 key features. - Eosinophilic infiltration of tissue. - Formation of extravascular granulomas. - Vasculitis. 2. Peripheral blood eosinophils are a requisite for diagnosis. 3. Inflammatory marker, IgE raised. **Medium Vessel Vasculitis:** **Polyarteritis Nodosa:** - Inflammatory necrotizing vasculitis that affects medium sized arteries preferentially at vessel bifurcations. - PAN affects multiple systems: skin, joints, gut, kidneys, although lungs are usually spared. **Classification:** **Cutaneous:** - Livedo reticularis that does not blanch with active pressure. - Ulcerations- Near the malleoli, calf digital ischemia: splinter haemorrhages. **Extracutaneous:** - Unexplained weight loss. - Arthralgia. - Abdominal pain - Hypertension. **Kawasaki Disease:** **Synonym:** Mucocutaneous lymph node syndrome. - It is an acute febrile illness with inflammation of medium sized blood vessels particularly coronary arteries.  **Clinical featuresioel-jnx30p\[y7u-0p\[ymr,\\t54rf:** - Fever (102-104◦F). - Erythematous rash. - Oral signs- strawberry tongue, cracked lips. - Eye signs- Redness of Bulbar conjunctive. - Lymphadenopathy. **Large Cell Vasculitis** **Gaint cell vasculitis:** Synonym: Temporal arteritis or granulomatous arteries. It is an inflammatory vasculopathy that manifests in large sized arteries (occurs in older people). **Classification**: 3 of the 5 criteria must be present. 1. Age at onset is greater than 50 years. 2. New onset of headache. 3. Temporal artery abnormality. 4. Elevated ESR (≥50nm/h). **Biopsy:** Vasculitis with predominant mononuclear cell inflammation/ granulomatous inflammation containing multinucleated giant cells. **Takayasu arteritis:** It is a chronic granulomatous vasculitis that predominantly involves aorta and its branches including pulmonary and coronary arteries. - Age of 40 years or younger at disease onset. - Claudication of the extremities. - Decreased pulsation of one or both brachial arteries. - Difference of at least 10mm Hg in systolic blood pressure between arms. - Bruit over one or both subclavian arteries or the abdominal aorta. - Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the upper or lower extremities that is not due to arteriosclerosis, fibromuscular dysplasia, or other causes. **REFERENCES:** 1. Nick j. Levell, Chetan Mukhtyar; In: Cutaneous Vasculitis; Ninth ed, Rook's textbook of Dermatology, 2016: 102: 102.1-102.36. 2. David A Wetter, Jan P. Dutz, Kanade Shinkai, Lindy P. Fox; In: Cutaneous Vasculitis; Fourth ed, Bolognia textbook for Dermatology, 2018: 409-439. 3. Col Biju Vasudevan, Asmita Sinha, Aneesh KP; In: Vasculitis; Fifth ed, IADVL textbook of dermatology,2022: 1343-1387.