Vasculitis

الرحيم الرحمن الله بسم�

VasculitisBy

Dr. Gamal Sultan

VasculitisVasculitis is defined as inflammation and

fibrinoid necrosis of the blood vessel wall It may present in a wide variety of clinical

manifestations depending on the localization and size of the vessels

involved, type of inflammatory infiltrate, and associated conditions

Dr. Gamal Sultan

Classification Some classification systems have focused on

the size of the vessels, OR the type of dominant inflammatory cells, such as

neutrophils, lymphocytes, and macrophages, affecting either small or large vessels.

Both types of classification scheme are imperfect, as overlap of vessels of various sizes may occur, and the type of inflammatory infiltrate may change over time

Dr. Gamal Sultan

ClassificationIn 1994, the Chapel Hill Consensus Conference (CHCC) created an alternative schema for classification of the major types of vasculitis Large-sized vessel vasculitis

Giant cell arteritis Takayasu's arteritis

Medium-sized vessel vasculitis Classic polyarteritis nodosa Kawasaki disease

Small-sized vessel vasculitis Wegener's granulomatosis Churg-Strauss syndrome Microscopic polyangiits Henoch-Schönlein purpura Essential cryoglobulinemia vasculitis Cutaneous leukocytoclastic angiitis

Dr. Gamal Sultan

ClassificationDr. Gam

al Sultan

Epidemiology the estimated the annual incidence of cutaneous vasculitis is

38.6 cases per million. the incidence is greater in women (50.4 cases per million) than

in men (26.0 cases per million). Cutaneous leukocytoclastic vasculitis, as defined by the CHCC,

was found to be 15.4 cases per million. A female predominance was observed with an estimated 24.2

cases per million cases compared to males (6.0 cases per million).

Dr. Gamal Sultan

Clinical Presentation Vasculitis, regardless of its cause,

most commonly presents as palpable purpura.

Palpable purpura is a raised, non-blanchable erythema and signifies extravasation of red cells outside of blood vessels

Dr. Gamal Sultan

Clinical Presentationin addition to this pathognomonic sign, lesions may including:

red macules, wheals, papules, nodules, ulcers , vesicles, and blisters

Dr. Gamal Sultan

Clinical Presentation The clinical presentation may vary, depending on the size of the

vessel involved. Cutaneous small- and medium-sized vessel disease may present

with a reticulate pattern that outlines the cutaneous vasculature.

Large vessels that supply a larger area of skin may present with widespread purpura and necrosis.

The lesions are distributed often symmetrically, most commonly on the lower legs, but can occur anywhere in the body. Lesions typically occur in areas of dependency but may occur in areas of trauma or pressure

Dr. Gamal Sultan

Clinical Presentation Mucosal involvement is rare, and if present, manifests itself in

the form of petechiae, hemorrhagic blisters, and ulcers. Usually, cutaneous lesions heal within one to four weeks if a

single initiating factor is the cause, for example, drug exposure. However, if cutaneous ulcers occur, healing may be prolonged.

There may also be residual scarring and hyperpigmentation. Vasculitis may, however, be recurrent and/or intermittent

with new crops of lesions appearing for months or years

Dr. Gamal Sultan

Clinical Presentation In some cases, the episode of cutaneous vasculitic lesions may

be associated with fever, malaise, arthralgia, and myalgia. The skin is often the only organ involved, but in some cases,

may be part of a systemic vasculitis correlated to an underlying disease.

Emboli leading to palpable lesions can occur in patients with endocarditis, left atrial myxoma, or due to cholesterol emboli.

Thrombocytopenia and disseminated intravascular coagulopathy present as widespread purpura; however, the purpura is usually non-palpable in these cases

Dr. Gamal Sultan

Histopathology Skin involvement in vasculitis may either

occur as a sole entity or as part of vasculitis involving other organ systems. In either case, the histology may be similar characterized by involvement of the post capillary venules

with endothelial cell swelling neutrophilic invasion of blood vessel walls presence of disrupted neutrophils

(leukocytoclasia) extravasation of red blood cells fibrinoid necrosis of the blood vessels

walls.

Dr. Gamal Sultan

Histopathology These features generated the term cutaneous

necrotizing vasculitis (CNV), which refers to leukocytoclastic vasculitis affecting the small and medium vessels that supply nutrients to the skin.

In later stages, thrombosis of affected small vessels is frequently observed, as well as hyalinization and fibrosis of vessel walls.

Dr. Gamal Sultan

Histopathology Based on histopathologic findings, CNV can be divided in two

major groups: leukocytoclastic form, due to deposition of immune complexes

on blood vessel wall (type III hypersensitivity reaction), and lymphomonocytic form, caused by immune-mediated vessel

injury. Some authors consider these two forms as different stages of the

same process. That is, over time a predominantly neutrophilic infiltrate will be replaced by lymphocytes or monocytes

Dr. Gamal Sultan

Etiology and Associations The etiology of a vasculitic syndrome is probably multifactorial with

influences on disease expression caused by ethnicity, genes (HLA and others), gender, and environment (ultraviolet exposure, infections, drugs, smoking, and surgery).

Frequent associations include infectious agents, medications, connective tissue diseases, and malignancies among others.

One half of all patients with cutaneous vasculitis, however, have no definite etiologic agent or associated disease.

Among the idiopathic vasculitides are Henoch-Schönlein purpura, urticarial vasculitis, erythema elevatum diutinum, nodular vasculitis, and cutaneous polyarteritis nodosa

Dr. Gamal Sultan

Diagnosis Although often clinically apparent, excluding other conditions that

may present similarly is the initial step in evaluating a patient with an eruption suggestive of vasculitis. Additionally, accurate diagnosis of the different forms of vasculitis will depend on the integration of a complete medical history thorough physical exam laboratory data

The aim of the investigations should be directed toward determining a potential cause or associated disorder, as well as determining the presence or absence of organ system involvement

Dr. Gamal Sultan

Laboratory Evaluation The laboratory evaluation in these situations may include

an assessment for ANCA, antinuclear antibodies, complement levels

cryoglobulins, rheumatoid factor. ASO antibodies, Hemoccult testing, antibodies for viral hepatitis, Urinalysis may detect glomerular involvement.

Radiographs, and if indicated, computerized topography and magnetic resonance imaging may be useful in diagnosing occult respiratory tract or neurologic disease

Dr. Gamal Sultan

Laboratory EvaluationDr. Gam

al Sultan

Skin Biopsy Histological evaluation of the skin lesions is paramount. A biopsy of the lesion may yield the typical features of cutaneous

vasculitis. Additional findings on histopathology may aid in suggesting an

underlying systemic disease. Thrombosis of the small blood vessels can be a result of septic

vasculitis, Tissue biopsies sent for culture may detect an infectious cause.

Immunofluorescence testing of skin to detect bound antibodies help in certain diseases. deposits of IgA within the vessel wall is observed in immunofluorescence studies of Henoch-Schönlein purpura.

Dr. Gamal Sultan

Clinical Syndromes of the Systemic

Vasculitis

Henoch-Schönlein Purpura

is the most common vasculitis in children.

an acute immunoglobulin A (IgA)–mediated disorder

characterized by a generalized vasculitis involving the small vessels of the skin, the gastrointestinal (GI) tract, the kidneys, the joints, and, rarely, the lungs and the central nervous system (CNS)

Dr. Gamal Sultan

Henoch-Schönlein Purpuraclinical presentation

The typical prodrome of HSP includes the following: Headache, Anorexia, Fever

Subsequently, symptoms develop, of which the following are the most common:

Rash (95-100% of cases), especially involving the legs; this is the hallmark of the disease

Abdominal pain and vomiting (35-85%) Joint pain (60-84%), especially involving the knees and ankles Subcutaneous edema (20-50%) Scrotal edema (2-35%) Bloody stools

Dr. Gamal Sultan

Henoch-Schönlein Purpurawork up

No specific diagnostic laboratory test is available to assess for markers of HSP. The following general laboratory tests may be helpful for excluding other diagnoses and evaluating renal function:

(ANA), (RF) , Factors VIII and XIII Urinalysis, (CBC), Platelet count, (ESR) Stool guaiac test, Blood urea nitrogen (BUN) and creatinine Amylase and lipase, Electrolytes, Plasma D-dimer Plasma thrombin-antithrombin (TAT) complex, prothrombin fragment (PF)-1, and PF-2 Prothrombin time (PT) and activated partial thromboplastin time (aPTT) Serum IgA, Immunocomplexes of IgG and IgA Antistreptolysin O (ASO), CH50, C3 and C4

Dr. Gamal Sultan

Henoch-Schönlein Purpurawork up

Imaging modalities that may be considered include the following:

Ultrasonography (abdominal, scrotal/testicular) Radiography (chest radiography; plain radiography of the abdomen;

contrast radiography of the small intestine; barium enema study) Magnetic resonance imaging (MRI; for assessing neurologic findings) Computed tomography (CT) of the head or abdomen

Other studies that may be warranted are as follows: Endoscopy Renal biopsy (particularly when nephrotic syndrome persists and when

renal function deteriorates)

Dr. Gamal Sultan

Henoch-Schönlein Purpuratreatment

Treatment remains primarily supportive in most cases include the following:

Ensuring adequate hydration Monitoring for abdominal and renal complications Treating minor symptoms of arthritis, edema, fever, or malaise Eating a bland diet Discontinuance of any drugs suspected of playing a causative role

Joint and soft tissue discomfort may be reduced by giving analgesics, such as:

Acetaminophen, Ibuprofen, Flurbiprofen, Ketoprofen, Naproxen

Dr. Gamal Sultan


Corticosteroids may be considered in:Persistent nephrotic syndromeCrescents in more than 50% of glomeruliSevere abdominal painSubstantial GI hemorrhageSevere soft tissue edemaSevere scrotal edemaNeurologic system involvement Intrapulmonary hemorrhage

Dr. Gamal Sultan


Other treatment regimens have included IV or oral steroids with or without any of the following:

Azathioprine Cyclophosphamide Cyclosporine Dipyridamole High-dose IV immunoglobulin G (IVIg) Danazol Fish oil

Plasmapheresis may be effective in delaying the progression of kidney disease.

Dr. Gamal Sultan

Wegener's Granulomatosis(Granulomatosis with Polyangiitis)

Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is a rare multisystem autoimmune disease of unknown etiology.

The pathologic hallmarks of GPA are vasculitis of the small- to medium-sized vessels, "geographic" necrosis, and granulomatous inflammation, particularly in the airways. The initial pathologic lesion is that of the granuloma believed to be caused by cellular immune processes

Dr. Gamal Sultan

Wegener's Granulomatosisclinical presentation

GPA has a spectrum of clinical presentations that includes multisystem affection

In addition, patients may report the following chronic, nonspecific constitutional complaints: Fevers, night sweats Fatigue, lethargy Loss of appetite Weight loss

Dr. Gamal Sultan

Wegener's Granulomatosisclinical presentation

Cutaneous manifestations variable and nonspecific and usually

affect the lower extremities Palpable purpura or skin ulcers (45%);

ulcerations may resemble pyoderma gangrenosum

Petechiae, vesicles, pustules, hemorrhagic bullae, livedo reticularis, digital necrosis, subungual splinter hemorrhages, and genital ulcers resembling squamous cell carcinoma have been reported

Dr. Gamal Sultan

Wegener's Granulomatosis work up

Routine laboratory tests are nonspecific in GPA. Results may include the following: Abnormal kidney function tests and urinalysis in patients with renal involvement Rheumatoid factor is positive in a low titer in two thirds of patients CBC: Mild normochromic normocytic anemia is present in 50% of patients; leukocytosis is

common, with a neutrophil predominance Elevated inflammatory markers (ESR, CRP)

Antineutrophil cytoplasmic antibody (ANCA) testing Cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) directed against PR3 is most specific

for GPA Some patients with GPA express perinuclear-staining ANCA (p-ANCA) specific for myeloperoxidase

(MPO) Combining immunofluorescence and ELISA enhances the sensitivity and specificity of a diagnosis

of an ANCA-associated vasculitis (AAV) to 96% and 98.5%, respectivel

Dr. Gamal Sultan

Wegener's Granulomatosis treatment

Induction of remission in GPA is approached as follows:Cyclophosphamide with high-dose glucocorticoids (criterion

standard)Rituximab with high-dose glucocorticoidsMethotrexate (oral or subcutaneous) with high-dose

glucocorticoids, in non–organ-threatening or non–life-threatening GPA

Plasma exchange may be considered in patients with rapidly progressive renal disease (serum creatinine level >5.65mg/dL) in order to preserve renal function

Dr. Gamal Sultan

Wegener's Granulomatosis treatment

Maintenance of remission

Once induction of remission has occurred, treatment for maintenance of remission should be continued for at least 18 months, often longer

Azathioprine (2 mg/kg/day) is safer than, and as effective as, cyclophosphamide in maintaining remission [6]

Methotrexate (20-25 mg weekly, oral or subcutaneous) has been used for the maintenance of remission if the serum creatinine level is less than 1.5 mg/dL

Leflunomide (20-30 mg/day) is as effective as methotrexate, but it is associated with more adverse effects

Dr. Gamal Sultan

Churg-Strauss Syndrome(Eosinophilic Granulomatosis with Polyangiitis)

Is defined by the presence of asthma, allergic rhinitis, pulmonary and systemic small-vessel vasculitis, extravascular granulomas, and blood eosinophilia.

The presence of autoantibodies directed against myeloperoxidase in neutrophils (p-ANCA) implicated in the disease pathogenesis

Allergic rhinitis and asthma are usually the first symptoms, followed by blood and tissue eosinophilia and later by infiltration of the lung and/or gastrointestinal tract.

The vasculitic lesion typically occurs three years after the onset of the allergic manifestations.

Dr. Gamal Sultan

Churg-Strauss Syndromeclinical presentation

The vascular inflammation in Churg-Strauss syndrome is more likely to affect small arteries, but veins may also be involved.

Heart, gastrointestinal tract, renal, and neurologic involvements are the main causes of death in these patients.

Dr. Gamal Sultan

Churg-Strauss Syndromeclinical presentation

Skin involvement (60%) may include the following:Leukocytoclastic angiitis

with palpable purpuraLivedo reticularis, skin

necrosis and gangrene, digital ischemia, urticaria, and subcutaneous nodules

Dr. Gamal Sultan

Churg-Strauss Syndrometreatment

Corticosteroids –form the backbone of treatment of people with EGPA. Nasal and inhaled steroids – As well as steroid tablets, people with

EGPA often need steroid sprays to treat their nose and sinus symptoms.

Cyclophosphamide – In people with severe EGPA and those who do not respond well to steroid treatment

Azathioprine and Methotrexate –added to reduce level of steroids without EGPA becoming more active.

Rituximab –used in severe EGPA that has not responded well to other treatment.

Dr. Gamal Sultan

Polyarteritis Nodosa

Classic polyarteritis nodosa (PAN or c-PAN) is a systemic vasculitis characterized Vascular lesions in medium-sized muscular arteries occur mainly at bifurcations and branch points.

Inflammation may start in the vessel intima and progress to include the entire arterial wall, destroying the internal and external elastic lamina, resulting in fibrinoid necrosis.

Aneurysms develop in the weakened vessel, carrying a subsequent risk for rupture and hemorrhage.

Thrombi may develop at the site of the lesions. As lesions progress, proliferation of the intima or media may result in obstruction and subsequent tissue ischemia or infarction.

Polyarteritis nodosa (PAN) spares large vessels, the smallest vessels, and the venous system

Dr. Gamal Sultan

Polyarteritis Nodosa

The pathogenesis of polyarteritis nodosa (PAN) is unknown. Hepatitis B virus (HBV) infection is strongly linked with PAN. Controversy surrounded the association of hepatitis C virus (HCV) with PAN. Loss-of-function mutations in CECR1, the gene that encodes adenosine

deaminase 2 (ADA2), have been associated with polyarteritis nodosa other infectious organisms have been reported in association with PAN or PAN-

like diseases, but causal evidence is inconsistent. These organisms include varicella-zoster virus, parvovirus B-19, cytomegalovirus, human T-cell leukemia virus, streptococcal species, Klebsiella species

Rheumatoid arthritis (RA) and Sjögren syndrome have been associated with PAN.

Dr. Gamal Sultan

Polyarteritis Nodosaclinical presentation

Polyarteritis nodosa (PAN) is an acute multisystem disease with a relatively short prodrome (ie, weeks to months). Delays in diagnosis are not uncommon.

The spectrum of disease ranges from single-organ involvement to fulminant polyvisceral failure

Constitutional and musculoskeletal symptoms of PAN include the following:

Fever, Myalgia, Malaise, Fatigue Anorexia and weight loss Arthralgia in large joints or, less commonly,

arthritis

Dr. Gamal Sultan


Cutaneous symptoms in PAN including: Livedo reticularis that does not blanch

with active pressure Ulcerations - Especially on the lower

extremities, near the malleoli and on the calf

Digital ischemia - May be accompanied by splinter hemorrhages and, sometimes, gangrene

Nodules - Usually on the lower extremities (like ulcers); nodules are the least common skin manifestation of PAN

Dr. Gamal Sultan


Dr. Gamal Sultan

Polyarteritis Nodosa work up

Laboratory findings in PAN are nonspecific but can help to establish the systemic nature of the disease. Findings include the following:

Elevated (ESR) and/or CRP- useful in evaluating some active disease but do not correlate with activity in all patients

CBC_ Leukocytosis, normochromic anemia, or thrombocytosis Hepatitis B surface antigen and hepatitic C serologies Elevated creatinine level, Mild proteinuria, Elevated levels of liver

enzymes Hypergammaglobulinemia - Found in 30% of patients with PAN

Dr. Gamal Sultan

Polyarteritis Nodosa work up

Cryoglobulins, circulating immune complexes, and decreased levels of serum complement (i.e., C3, C4) observed in patients with HBV-related PAN but are uncharacteristic of idiopathic PAN.

CSF findings often are usually normal in PAN, but polymorpho-nuclear pleocytosis can be seen when with meningeal signs.

ANCA testing is rarely positive in PAN. If ANCA testing is positive, the tests more commonly show a perinuclear (rather than cytoplasmic) pattern and antibodies to proteinase-3 and myeloperoxidase will be negative.

ANA and RF are generally negative, but low positive titers may be detected.

Dr. Gamal Sultan

Polyarteritis Nodosa treatment

Like systemic PAN, the optimal management for cutaneous PAN has not been established.

Expert recommendations include agents such as NSAIDs, colchicine, and dapsone.

In more severe cases, steroids and immunosuppressive agents such as cyclophosphamide may be used.

Reports of success with other agents such as mizoribine, mycophenolate, and pentoxifylline have been published.

Dr. Gamal Sultan

Kawasaki Disease

Kawasaki disease (KD) is an acute febrile vasculitic syndrome of early childhood.

Kawasaki disease is best regarded as a generalized vasculitis that involves small- to medium-sized arteries.

Although the vasculitis is most pronounced in the coronary vessels, it can also occur in veins, capillaries, small arterioles, and larger arteries

The etiology of Kawasaki disease remains unknown. At present, most evidence indicates that the causative agent is probably infectious. However, autoimmune reactions and genetic predisposition have been suggested

Dr. Gamal Sultan

Kawasaki Disease clinical presentation

Most children with Kawasaki disease are brought to medical attention because of prolonged fever.

Diagnosis of complete cases requires fever of at least 5 days’ duration (though many believe that the diagnosis can be made earlier in otherwise classic presentations)

Dr. Gamal Sultan


The diagnostic criteria established by the American Heart Association (AHA) include fever lasting longer than 5 days (fever is an absolute criterion) and 4 of the 5 main clinical features. The 5 major clinical findings are as follows:

Changes in the peripheral extremities: Initial reddening or edema of the palms and soles, followed by membranous desquamation of the finger and toe tips or transverse grooves across the fingernails and toenails (Beau lines)

Polymorphous rash (not vesicular): Usually generalized but may be limited to the groin or lower extremities

Oropharyngeal changes: Erythema, fissuring, and crusting of the lips; strawberry tongue; diffuse mucosal injection of the oropharynx

Bilateral, non-exudative, painless bulbar conjunctival injection Acute non-purulent cervical lymphadenopathy with lymph node diameter

greater than 1.5 cm, usually unilateral

Dr. Gamal Sultan


Dr. Gamal Sultan

Kawasaki Disease work up

No specific laboratory test is used to diagnose Kawasaki disease (i.e., [ESR], [CRP] and alpha1-antitrypsin levels) are elevated at first; then return to baseline 6-10 weeks after the onset of the illness.

More recently, 2 urine proteins hold as biomarkers of Kawasaki disease: meprin A or filamin C.

Elevated macrophage migration factor (MIF) and (IL-6) may be useful markers in the acute stages of Kawasaki disease.

(CBCs) normochromic anemia, (WBC) is moderate to high (50% of patients have a WBC greater than 15,000/µL), with a left shift

Thrombocytopenia is associated with severe coronary artery disease and myocardial infarction. rarely, it may be associated with disseminated intravascular coagulation.

Serum cholesterol, high-density lipoprotein, and apolipoprotein A levels are decreased;

Dr. Gamal Sultan

Kawasaki Disease treatment

The principal goal of treatment is to prevent coronary artery disease and to relieve symptoms. Full doses of intravenous immunoglobulin (IVIG) are the mainstay of treatment.

Aspirin (high-dose, followed by low-dose) has traditionally been standard. Other medications include the following:

Corticosteroids: Typically in patients unresponsive to standard therapies Methotrexate or cyclophosphamide: In IVIG-resistant cases Infliximab: In refractory cases with coronary aneurysms [10]

Antiplatelet medications (eg, clopidogrel, dipyridamole Anticoagulants (eg, warfarin, low-molecular-weight heparin A new treatment ulinastatin (UTI), a neutrophil elastase inhibitor used to treat patients

with circulatory shock or pancreatitis.

Dr. Gamal Sultan

Giant Cell Arteritis

Giant cell arteritis (GCA), or temporal arteritis, is a systemic inflammatory vasculitis of unknown etiology that occurs in older persons and can result in a wide variety of systemic, neurologic, and ophthalmologic complications.

GCA is the most common form of systemic vasculitis in adults. GCA typically affects the superficial temporal arteries—hence the

term temporal arteritis. In addition, GCA most commonly affects the ophthalmic, occipital, vertebral, posterior ciliary, and proximal vertebral arteries.

It has also been involved medium- and large-sized vessels, including the aorta and the carotid, subclavian, and iliac arteries

Dr. Gamal Sultan

Giant Cell Arteritisclinical presentation

The most commonly reported symptoms: Headache (initial in 33%, present in

72%) Neck, torso, shoulder, and pelvic

girdle pain that is consistent with polymyalgia rheumatica (PMR; initial in 25%, present in 58%)

Fatigue and malaise (initial in 20%, present in 56%)

Jaw claudication (initial in 4%, present in 40%)

Fever (initial in 11%, present in 35%)

Less common symptoms: Limb claudication (8%) Transient ischemic attacks (TIAs) or

stroke (4-7%) Scintillating scotoma (5%)

Carpal tunnel syndrome (5%) or other peripheral neuropathies

Tongue or throat claudication (4%) Diplopia or ptosis (2%), Tongue

numbness (2%) Myelopathic symptoms (< 1%) Affective or psychotic symptoms Facial pain (rare), Scalp necrosis

(rare), Tongue necrosis (rare)

Dr. Gamal Sultan

Giant Cell Arteritisclinical presentation

The diagnostic criteria for GCA issued by the American College of Rheumatology (the presence of 3 or more yields a diagnostic sensitivity of 93.5% and specificity of 91.2%): Age 50 years or older New-onset localized headache or localized head pain Temporal artery tenderness to palpation or decreased

pulsation ESR of 50 mm/h or higher Positive arterial biopsy results (vasculitis characterized by

mononuclear infiltration or granulomatous inflammation, usually with multinucleated giant cells)

Dr. Gamal Sultan

Giant Cell Arteritistreatment

The universally accepted treatment of (GCA) is high-dose corticosteroid therapy

The dose of prednisone should be initiated at approximately 1 mg/kg body weight for 1 month. The response to therapy should be rapid and dramatic, once the ESR has normalized.The dose of prednisone should be tapered slowly 1-2 years of therapy.

steroid-sparing immunosuppressive therapy such as methotrexate has been modest, but may be considered in patients with relative contraindications to steroids, such as brittle diabetics.

low-dose acetylsalicylic acid (ASA) has been shown to decrease the incidence of cerebrovascular accidents and visual loss

Dr. Gamal Sultan

Takayasu's Arteritis

Takayasu arteritis is a rare, systemic, inflammatory large-vessel vasculitis of unknown etiology that most commonly affects women of childbearing age.

It is defined as "granulomatous inflammation of the aorta and its major branches"

Dr. Gamal Sultan

Takayasu's Arteritisclinical presentation

The presentation of Takayasu arteritis is heterogeneous. Approximately 10% of patients are asymptomatic, the diagnosis is suggested only by abnormal vascular

findings on physical exam.

Constitutional symptoms include the following: Headache (50-70%) Malaise (35-65%) Arthralgias (28-75%) Fever (9-35%) Weight loss (10-18%)

Dermatologic manifestations include the following:

Erythema nodosum (6-19%) Ulcerated subacute nodular lesions (<2.5%) Pyoderma gangrenosum (<1%)

Dr. Gamal Sultan

Takayasu's Arteritistreatment

Medical management of Takayasu arteritis depends on the disease activity and the complications that develop

The two most important aspects of treatment are controlling the inflammatory process and controlling hypertension

Corticosteroids are the mainstay of therapy for active Takayasu arteritis

IL-6 receptor inhibitor Rituximab, a chimeric IgG1 antibody that binds to CD20 expressed on

the surface of B cells, has been shown to improve clinical signs and symptoms of Takayasu arteritis

Cytotoxic agents are used for steroid resistant or relapsing.

Dr. Gamal Sultan

Erythema Elevatum Diutinum

Erythema elevatum diutinum (EED) is a rare type of leukocytoclastic vasculitis

The pathophysiology of erythema elevatum diutinum is not well understood.

the lesions are thought to be caused by the deposition of immune complexes in small blood vessels.

It can occur at any age. However, it is mostly an adult disease that occurs from the third to sixth decade of life.

Dr. Gamal Sultan

Erythema Elevatum Diutinumclinical presentation

Patients with erythema elevatum diutinum (EED) usually present with persistent, firm lesions on the extensor surfaces of their skin, especially over the joints.

These lesions are most often nodules and round or oval plaques. However, on rare occasions, blisters and ulcers may also appear.

Dr. Gamal Sultan

Erythema Elevatum Diutinumclinical presentation

Upon physical examination, erythema elevatum diutinum lesions are generally found symmetrically on the extensor surfaces of the skin, especially over the joints.

Clinical studies show a preference for the extensor surfaces of the hands, wrists, elbows, ankles, Achilles tendons, fingers, and toes.

Dr. Gamal Sultan

Erythema Elevatum Diutinum work up

Electron microscopy show changes consistent with leukocytoclastic vasculitis.

Direct immunofluorescence show deposits of complement, immunoglobulins (IgG, IgA, IgM), and fibrin intravascularly and perivascularly.

Immunoelectrophoresis (IEP) used to identify possible gammopathies. A positive reaction to skin testing with streptokinase and streptodornase at 4

and 24 hours help determine a causative association with bacterial infection. ESR is often elevated. Antineutrophil cytoplasmic antibodies of IgA class become a helpful

paraclinical marker of disease

Dr. Gamal Sultan

Erythema Elevatum Diutinumtreatment

Dapsone (diaminodiphenylsulfone) revolutionized the treatment of patients with (EED). Several studies have shown a good response to dapsone, therefore making it the treatment of choice.

Systemic steroids generally have not been found to be effective. Sulfapyridine has had similar effects as dapsone. Niacinamide was found (in one study) to be helpful in suppressing EED. Intermittent plasma exchange (PLEX) was shown to control IgA

paraproteinemia associated with EED. The IgA levels responded to PLEX treatment, followed by consolidative doses of cyclophosphamide. This treatment might be promising for the control of severe EED that is not controlled by dapsone.

Dr. Gamal Sultan

Urticarial Vasculitis

an eruption of erythematous wheals that clinically resemble urticaria but histologically show changes of leukocytoclastic vasculitis.

Urticarial vasculitis may be divided into normocomplementemic and hypocomplementemic variants.

Both subsets can be associated with systemic symptoms (eg,angioedema, arthralgias, abdominal or chest pain, fever, pulmonary disease, renal disease, episcleritis, uveitis, and Raynaud phenomenon).

The hypocomplementemic form more often is associated with systemic symptoms and has been linked to connective-tissue disease (ie, [SLE]).

Dr. Gamal Sultan

Urticarial Vasculitis

The pathophysiology of urticarial vasculitis is similar to other forms of cutaneous small vessel leukocytoclastic vasculitis.

Urticarial vasculitis is a type III hypersensitivity reaction Patients with hypocomplementemic urticarial vasculitis are more

likely to show autoantibodies to C1q and vascular endothelial cells.

The presence of antineutrophilic cytoplasmic antibodies is rare. Many patients ultimately prove to have SLE. Other etiologies include drug reactions and parasitic infections

Dr. Gamal Sultan

Urticarial Vasculitisclinical presentation

Patients with urticarial vasculitis present with an urticarial eruption, often accompanied by a painful or burning sensation.

Lesions are generalized wheals or erythematous plaques, occasionally with central clearing, lasting for more than 24 hours in a fixed location (in contrast to urticaria, which resolves in minutes to hours or migrates continually).

Dr. Gamal Sultan

Urticarial Vasculitisclinical presentation

Petechiae may be noted within the lesions, and they may resolve with ecchymoses or postinflammatory hyperpigmentation.

Patients may have photosensitivity Lymphadenopathy, arthralgia,

fever angioedema (40%) abdominal pain dyspnea, and pleural and

pericardial effusions.

Dr. Gamal Sultan

Urticarial Vasculitis work up

Check CH50, C3, C4, Clq, and antibodies to Clq in urticarial vasculitis patients. If these test results are positive, evaluate renal function and urinalysis to check for the effects of vasculitis on the kidneys.

If the history suggests viral infections, obtain hepatitis B, hepatitis C Direct immunofluorescence may show deposition of vascular C3, fibrin, and

immunoglobulins. A lupus band may be detected in patients with underlying lupus erythematosus. ANA and lupus serologies. Anti-SSA and anti-SSB may be seen in patients with

Sjögren syndrome. antineutrophilic cytoplasmic antibodies are generally negative, and, if they

are positive, the possibility of Wegener granulomatosis or microscopic polyangiitis should be considered.

Dr. Gamal Sultan

Urticarial Vasculitistreatment

Treatment is based on systemic effects of the disease, extent of cutaneous involvement, and previous response to treatment.

Antihistamines or nonsteroidal anti-inflammatory drugs (NSAIDs) For patients with cutaneous involvement may provide symptomatic relief.

Colchicine, hydroxychloroquine, or dapsone , If these agents fail may be effective.

glucocorticoids If all other treatment modalities have failed or if the patient has systemic involvement

Rituximab-based treatment can provide higher response rates compared with corticosteroids and conventional immunosuppressive agents

Dr. Gamal Sultan

Cryoglobulinemia

Cryoglobulins are single or mixed immunoglobulins that undergo reversible precipitation at low temperatures. the potential clinical manifestations vary by cryoglobulin type.

Cryoglobulinemia is characterized by the presence of cryoglobulins in the serum. This may result in a clinical syndrome of systemic inflammation (most commonly affecting the kidneys and skin) caused by cryoglobulin-containing immune complexes.

Cryoglobulinemia classified based on cryoglobulin composition as follows: Type I cryoglobulinemia, is the result of a monoclonal immunoglobulin, usually (IgM) or,

less frequently,(IgG), (IgA), or light chains. Types II and III cryoglobulinemia (mixed cryoglobulinemia) contain rheumatoid

factors (RFs), which are usually IgM and, rarely, IgG or IgA. The actual RF may be monoclonal (in type II cryoglobulinemia) or polyclonal (in type III cryoglobulinemia).

Types II and III cryoglobulinemia represent 80% of all cryoglobulins.

Dr. Gamal Sultan

Cryoglobulinemiaclinical presentationtype immunoglobulin Underlying

associationClinical finding

I Monoclonal IgM or IgG(no rheumatoid factor activity)

Lymphoproliferativedisorders (LPD), plasma cell dyscrasias

Raynaud’s phenomenon, purpura, acrocyanosis, arterial thrombosis

II (MIXED) Monoclonal IgM (or IgG) with polyclonal IgG (have rheumatoid factor activity)

HCV , autoimmune connective tissue diseases, LPD

Vasculitis with palpable purpura,arthralgias, glomerulonephritis,peripheral neuropathy

III (MIXED)

Polyclonal IgM complexed with polyclonal IgG (have rheumatoid factor activity)

Dr. Gamal Sultan

Cryoglobulinemiaclinical presentation

Skin manifestations include the following: Ischemic necrosis (40% in type I, 0-20% in mixed

types) Palpable purpura (15% in type I, 80% in mixed

types) Livedoid vasculitis (1% in type I, 14% in type III) Cold-induced urticaria (15% in type I, 10% in type

III) Hyperkeratotic spicules in areas exposed to cold Scarring of tip of nose, pinnae, fingertips, and toes Acrocyanosis Nailfold capillary abnormalities

Dr. Gamal Sultan

Cryoglobulinemiaclinical presentation

Dr. Gamal Sultan

Cryoglobulinemia work up

To evaluate for serum cryoglobulins, the blood specimen must be collected in warm tubes (37°C) in the absence of anticoagulants. Allow the blood sample to clot before removal of serum with centrifugation (at 37°C).The period required for the serum sample to incubate (at 4° C) depends on the type of cryoglobulin present:

Type I precipitate within the first 24 hours (at concentrations >5 mg/mL)

Type III require 7 days to precipitate a small sample (<1 mg/mL)

Additional laboratory findings in cryoglobulinemia include the following:

Urinalysis: CBC, serum creatinine levels and

electrolyte Liver function studies (RF): positive in types II and III (ANA),(ESRComplement evaluation (CH50, C3, C4):

Patients may display hypo-complementemia (low C4 levels).

Dr. Gamal Sultan

Cryoglobulinemiatreatment

The overall aim of therapy is treatment of any underlying condition and general suppression of the immune response.

Mild anti-inflammatory medications (e.g. NSAIDs) are effective in mild cases

corticosteroid therapy is reserved for the more severe or refractory cases.

Cyclophosphamide used as a steroid-sparing agent or administered concomitantly in severe cases of vasculitis, particularly in patients with renal disease.

Azathioprine is commonly used as a steroid-sparing agent, and chlorambucil has also been used for severe vasculitis

Dr. Gamal Sultan

Health & Medicine

Vasculitis