Pediatrics Immunology & Rheumatology, PDF

Pediatrics (Immunology & Rheumatology) APPROACH TO A CHILD WITH SUSPECTED IMMUNODEFICIENCY 371  Pediatrics (Immunology & Rheumatology) ❑ Lymphoid Progenitor for Lymphocytes Becomes T-cell in Thymus - Important in Cellular Immunity - Develop into...

Pediatrics (Immunology & Rheumatology) APPROACH TO A CHILD WITH SUSPECTED IMMUNODEFICIENCY 371  Pediatrics (Immunology & Rheumatology) ❑ Lymphoid Progenitor for Lymphocytes Becomes T-cell in Thymus - Important in Cellular Immunity - Develop into CD4, CD8 or other cells - Secretes cytokines, interleukins, etc. - Assists B-cells in making immunoglobulins Becomes B-cell in Bone Marrow - Begins with IgM - Matures to form other immunoglobulins IgA, IgE, or IgG (with subclasses IgG1-4) - Mature cell is Plasma cell. - Immunoglobulins used to surround antigens for phagocytosis - Responsible for Specific immunity (and memory). ❑ Neutrophils and Macrophages - Surround and gobble up organisms, often those surrounded by immunoglobulins (Phagocytosis and Opsonization). - Part of natural or innate or nonspecific immunity. ❑ Complement system - Cascade of plasma proteins which aid in chemotaxis and opsonization. 372  Pediatrics (Immunology & Rheumatology) When to suspect immunodeficiency Unusual, chronic, or recurrent infections such as: 1. ≥ 1 systemic bacterial infection (sepsis, meningitis). 2. ≥ 2 serious respiratory or documented bacterial infections (cellulitis, abscesses, draining otitis media, pneumonia) within 1 yr. 3. Serious infection occurring at unusual sites (liver, brain abscess). 4. Infection unusual pathogen. 5. Infection with common childhood pathogen but of unusual severity 6. Family history of early infant death or a known immunodeficiency disorder. Additional clues: 1. FTT with or without chronic diarrhea 2. Persistent infection after receiving live vaccines 3. Chronic oral or cutaneous moniliasis Why diagnosis is difficult 1. Immunodeficiency diseases are not screened for at any time during life 2. Extensive use of antibiotics may mask the classic presentation. 3. Most affected do not have abnormal physical features Classification of Immunodeficiencies Primary immunodeficiency (Hereditary) Secondary immunodeficiency (Acquired) ▪ Predominant antibody defect ▪ Systemic disorder: ▪ Combined T- and B-cell defect - Diabetes, ▪ Other cellular immunodeficiency - HIV infection, ▪ Complement defect - Undernutrition, ▪ Phagocytic defect ▪ Immunosuppressive Treatment : ▪ Diseases of immune dysregulation - cytotoxic chemotherapy, - Bone marrow transplant, - Radiation therapy, - Corticosteroids etc) ▪ Prolonged serious illness (critically ill, hospitalized patients) 373  Pediatrics (Immunology & Rheumatology) Primary immune deficiency (PID) Definition: ▪ A group of disorders characterized by an impaired ability to produce normal immune response. ▪ Most of these disorders are caused by mutations in genes involved in the development and function of immune organs, cells, and molecules. Clinical features: ▪ Recurrent infection, high risk of auto immune diseases, allergy and malignancy. Classification T-cell disorders B-cell defects ▪ Severe combined immunodeficiency ▪ XL agammaglobulinemia ▪ Wiskott aldrich syndrome (Xp11) ▪ Common variable immunodeficiency ▪ Ataxia telengectiasia (11g) ▪ Selective IgA deficiency ▪ Digeorge anomaly ▪ AR agammaglobulinemia ▪ Hyper-IgM syndromes - XL Phagocyte disorders Complement disorders ▪ Chronic granulomatous disease ▪ C1q deficiency ▪ Leukocyte adhesion defect ▪ Factor I deficiency ▪ Chediac higashi syndrome ▪ Factor H deficiency ▪ Mveloperoxidase deficiency ▪ Factor D deficieney ▪ Cyclic neutropenia (elastase defect) ▪ Properdin deficiency The European Society of Immunodeficiency's (ESID) 10 warning signs for suspicion of PID: 1. 4 or more new ear infections within 1 year. 2. 2 or more serious sinus infections within 1 year. 3. 2 or more pneumonias within 1 year. 4. 2 or more deep-seated infections including septicemia. 5. 2 or more months on antibiotics with little effect. 6. Failure to gain weight or grow normally. 7. Recurrent, deep skin or organ abscesses. 8. Persistent thrush in mouth or fungal infection on skin. 9. need for intravenous antibiotics to clear infection 10.A family history of PID. 374  Pediatrics (Immunology & Rheumatology) Characteristic features of PID Predominant T-cell defect Age at onset Specific pathogen Affected organ Special feature Early age, ▪ Bacteria: Gram +ve and ▪ Extensive ▪ Failure to thrive 2-6 months Gram -ve, mycobacteria. mucocutaneous ▪ Protracted diarrhea ▪ Virus: CMV, EBV, candidiasis ▪ Post-vaccination Varicella, adenovirus. ▪ Lungs disseminated BCG ▪ Fungus: candida, ▪ GI or varicella pneumocystis jiroveci ▪ Hypocalcemic tetany in infancy ▪ Graft vs host disease Predominant B-cell defect Age at onset Specific pathogen Affected organ Special feature After ▪ Bacteria: ▪ Recurrent sinopulmonary ▪ Autoimmunity maternal Ab pneumococci, infection ▪ Post-vaccination diminish, streptococci, ▪ Chronic GI symptoms, paralytic polio usually after staphylococci, malabsorption ▪ Lymphoreticular 5-7 months mycoplasma ▪ Arthritis malignancy: of age ▪ Virus: enterovirus ▪ Enteroviral lymphoma, ▪ Parasite: Giardia, meningoencephalitis thymoma Cryptosporidia Phagocyte (Granulocyte) defect Age at onset Specific pathogen Affected organ Special feature Early onset ▪ Bacteria: staph, ▪ Skin: ▪ Prolonged pseudomonas, abscess, impetigo, cellulitis attachment of Klebsiella, ▪ Lymph node: umbilical cord. salmonella suppurative adenitis. ▪ Poor wound ▪ Fungi: candida, ▪ Oral cavity: healing. nocardia, gingivitis, mouth ulcer. aspergillus Complement defect Age at onset Specific pathogen Affected organ Special feature Any age ▪ Bacteria: ▪ Infection: ▪ Autoimmune disorder: Pneumococci, meningitis, arthritis, SLE, Vasculitis, Neisseria septicemia, scleroderma, recurrent dermatomyositis, sinopulmonary glomerulonephritis infections 375  Pediatrics (Immunology & Rheumatology) IUIS Classification Primary Immunodeficiency Disease Category Group I Immunodeficiencies affecting cellular and humoral immunity II Combined immunodeficiences with associated or syndromic features III Predominantly antibody deficiencies IV Diseases of immune dysregulation V Congenital defects of phagocyte number of function VI Defects in intrinsic or innate immunity VII Autoinflammatory disorders VIII Complement deficiencies IX Bone marrow failure X Phenocopies of inborn errors of immunity Common clinical features: ▪ Recurrent respiratory tract infections ▪ Severe bacterial infection ▪ Persistent infection with incomplete response ▪ Persistent sinusitis/mastoiditis ▪ Failure to thrive / Growth retardation ▪ Diarrhea/malabsorption ▪ Occasionally present: - Lymphadenopathy - Hepatosplenomegaly - Recurrent meningitis - Pyoderma - Deep infections: osteomyelitis, cellulitis Age at presentation Newborn and young infant In Infant and young children In older children (0-6 months) (6 months - 5 years) (>5 years) and adults ▪ SCID ▪ CGD ▪ X-linked ▪ LAD ▪ Hyper IgE syndrome agammaglobulinemia ▪ DiGeorge anomaly ▪ Chediak-Higashi syndrome ▪ Ataxia telangiectasia ▪ Wiskott-Aldrich syndrome ▪ Chronic mucocutaneous ▪ Common variable ▪ X-linked hyper IgM candidiasis immunodeficiency syndrome ▪ X-linked lymphoproliferative syndrome 376  Pediatrics (Immunology & Rheumatology) Screening immunologic testing in child with recurrent infection CBC with DLC & ESR (Hemogram) Absolute neutrophil count Normal results rules out: - Congenital or acquired neutropenia - Leucocyte adhesion defect (persistently elevated ANC, LAD is suspected even in absence of signs of infection) Absolute lymphocyte count Normal results rules out: T-cell defect Platelet count Normal results rules out: WAS ESR Normal results: chronic bacterial or fungal infection unlikely ❑ Screening test for T-cell defect Absolute lymphocyte count Normal results rules out T-cell defect Flow cytometry To check for naive T-cells (CD3+CD45RA) ❑ Screening test for B-cell defect IgA If abnormal, measure IgM, IgG Antibody tire to protein & polysaccharides antigens (Isohemagglutinins and Ab to blood group substances, vaccine antigens) ❑ Screening test for phagocytic cell disorder Absolute neutrophil count Respiratory burst assay ❑ Screening test for complement deficiency CH50 Measures intactness of the entire complement pathway. Low value indicates complement deficiency. General management of PID: 1. Diet 2. Avoidance of pathogens (germ-free care) 3. Antibiotics. 4. Avoid whole blood transfusion in combined immune deficiency disorders (GVHR). 5. Avoid live virus vaccines and BCG 377  Pediatrics (Immunology & Rheumatology) Immunoglobulin replacement a) Treatment of severe antibody disorders  IVIG: 400-600 mg/kg/m.  Frozen plasma: 10 ml/kg/m b) Caution with administration of blood product if selective IGA deficiency. Specific treatment of cellular deficiency 1) Bone marrow transplantation 2) Replacement therapy:  Enzyme replacement  Gene therapy  Thymic hormones  Cytokines 3) Fetal thymus transplantation Specific treatment of phagocytic disorders: 1) Interferon gamma for CGD. 2) Granulocyte transfusion. 378  Pediatrics (Immunology & Rheumatology) Defects of antibody production X-linked (Bruton) agammaglobulinemia Definition: ▪ X-linked (Bruton) agammaglobulinemia (XLA) is a profound defect in B-cell development which leads to an absence of circulating B-cells and thus leads to severe hypogammaglobulinemia with small-to-absent tonsils and no palpable lymph nodes. Cause: ▪ It results from mutations in a gene on the X chromosome that encodes Bruton tyrosine kinase (BTK) essential for B-cell development and maturation. Clinical findings: ▪ Boys with pyogenic sinopulmonary infections ▪ Recurrent infections with encapsulated bacteria. Diagnosis: ▪ Clinical presentation + ▪ Lymphoid hypoplasia on exam; ▪ All immunoglobulins severely depressed; ▪ Flow cytometry shows absence of circulating B-cells; ▪ Gene sequencing for specific mutation. Treatment: ▪ Appropriate use of antibiotics + regular monthly IVIG. Common variable immunodeficiency Definition: ▪ Common Variable Immunodeficiency (CVID) is hypogammaglobulinemia with phenotypically normal B-cells; blood B-lymphocytes do not differentiate into IG producing cells. Clinical findings: ▪ Boy or girl (equal sex distribution) with later onset infections, less severe; clinically similar to XLA, but rare echovirus meningoencephalitis. Diagnosis: ▪ Clinical presentation + ▪ Serum IG and antibody deficiencies as profound or less than in XLA; ▪ Normal sized lymphoid tissue; ▪ Later autoimmune disease and malignancy (lymphoma). Treatment: ▪ Need to be screened for anti-IgA antibodies (as in selective IgA deficiency) → if present, therapy consists of the one IG preparation available that contains no IgA. 379  Pediatrics (Immunology & Rheumatology) Selective IgA deficiency Definition: ▪ Selective IgA deficiency is the most common immunodeficiency. ▪ It is caused by the absence or near absence of serum and secretory IgA with phenotypically normal B-cells Clinical findings: ▪ Same bacteria as others with most infections in respiratory, GI and urogenital tracts; Giardiasis is common Diagnosis: ▪ Very low-to-absent serum IgA with other IGs normal; as with CVID, ▪ Incidence of autoantibodies, autoimmune disease and malignancy increased; ▪ Serum antibodies to IgA can cause severe anaphylactic reactions if any blood product with IgA is administered (NOT a trans fusion reaction) Treatment: ▪ IVIC is not indicated (95-99% is IgG) because if usual IVIG (containing IgA) product is given, patients are at risk for severe reaction. ▪ Additionally, because it is specifically an IgA deficiency, the IVIG product with the IgA removed cannot be used. ▪ Treat the infections (generally milder). 380  Pediatrics (Immunology & Rheumatology) Defects of cellular immunity (T-cell defects) DiGeorge syndrome (thymic hypoplasia) Definition: ▪ DiGeorge syndrome is thymic and parathyroid hypoplasia to aplasia from dysmorphogenesis of the 3rd and 4th pharyngeal pouches. ▪ Predominant T cell defect. ▪ Other structures are also involved: great vessel anomalies (right-sided aortic arch, interrupted aortic arch), esophageal atresia, bifid uvula, congenital heart disease (conotruncal malformations, septal defects), facial dysmorphism (short philtrum, thin upper lip, hypertelorism, mandibular hypoplasia, low-set, often notched ears), and cleft palate. Clinical findings: ▪ From almost no infections with normal growth to severe opportunistic infections and graft-versus-host disease. ▪ In most, initial presentation is neonatal hypocalcemic seizures (neonatal tetany). Diagnosis: ▪ Most with only moderately low absolute lymphocyte counts with variably decreased CD3 T-lymphocytes per the degree of thymic hypoplasia. Treatment: ▪ Complete form correctable with either culture unrelated thymic tissue transplants or bone marrow or peripheral blood transplantation from HLA- identical sibling. 381  Pediatrics (Immunology & Rheumatology) Combined antibody and cellular immunodeficiency Severe combined immunodeficiency Definition: ▪ Severe Combined Immunodeficiency (SCID) is the absence of all adaptive immune function, and in some, natural killer cells due to diverse mutations. ▪ It is the most severe immunodeficiency known. ▪ Characterized by the disturbed development of functional T-cells and B-cells caused by numerous genetic mutations. ▪ SCID involves defective antibody response due to either direct involvement with B-lymphocytes or through improper B-lymphocyte activation due to non-functional T-helper cells. ▪ Impairment of both cellular and humoral response Clinical findings: ▪ Severe bacterial, viral, or fungal infections early in life and often present with interstitial lung disease, chronic diarrhea, and failure to thrive. ▪ First 1-3 months of life with recurrent/persistent diarrhea and opportunistic infections that may lead to death; also at risk for graft-versus-host disease from maternal immunocompetent T-cells that crossed the placenta in utero. ▪ If patient continues to live without treatment, typical B-cell related infections will develop ▪ If untreated, usually die within one year, considered pediatric emergency needs hematopoietic stem cell transplantation Diagnosis: ▪ All patients have lymphopenia from birth, ▪ Low-to-absent T-cells, ▪ Low-to-absent serum IGs and no antibodies after immunizations. ▪ The X-linked form has a low percentage of T and NK cells. Treatment: ▪ Stem cell transplantation (HILA-identical or T-cell depleted half matched parental); without it, most patients will die in first year but if diagnosed in first 3-4 months and treated, 94% will survive. ▪ The ADA form and X-linked have been treated with somatic gene therapy. 382  Pediatrics (Immunology & Rheumatology) Combined immunodeficiency Definition: ▪ Combined immunodeficiency is the presence of low but not absent T-cell function and low but not absent antibodies; patients survive longer but have failure-to-thrive and still die relatively early in life which are: Wiskott-Aldrich syndrome ❑ Genetics: X-linked recessive. Mutations in Wiskott-Aldrich syndrome protein (WASP) gene, a cytoplasmic protein necessary for normal B-and T-cell signaling ❑ Clinical findings: 1) Thrombocytopenia presenting in neonatal period or early infancy 2) Atopic dermatitis (eczema) 3) Recurrent infections in first year of life ❑ Diagnosis: ▪ Clinical and molecular genetics; ▪ Most common IG pattern is low IgM, high IgA and IgE and normal to slightly low IgG and variably reduced T-cells. ❑ Treatment: ▪ Rare survival beyond adolescence (bleeding, infections and EBV associated malignancies and autoimmune complications) without a bone marrow transplant. Ataxia-telangiectasia ❑ Definition: ▪ Ataxia-telangiectasia is a moderately depressed response to T- and B-cell mitogens, moderately reduced CD3 and CD4 T-cells with normal or increased percentages of CD8, T-helper cell and intrinsic B-cell defects, and hypoplastic thymus. ❑ Genetics: AR. A DNA repair defect that frequently results in humoral and cellular immunodeficiency. ❑ Clinical findings: 1) Ataxia evident with onset of walking and progresses until age 10-12 years. 2) Oculocutaneous telangiectasias. 3) Recurrent sinopulmonary infections. ❑ Investigation ▪ IgA and serum alpha-1 fetoprotein levels are measured. ❑ Treatment: supportive care with prophylactic antibiotics or with immunoglobulin. 383  Pediatrics (Immunology & Rheumatology) Disorders of phagocytic function Chronic granulomatous disease Definition: ▪ Chronic granulomatous disease (CGD) is when neutrophils and monocytes phagocytize but cannot kill catalase-positive microorganisms as a result of a defect in production of oxidative metabolites. ▪ White blood cells (WBCs) do not produce hydrogen peroxide, superoxide, and other activated oxygen compounds because NADPH oxidase activity is deficient, Phagocytic function is defective Clinical findings: ▪ Variable age on onset and severity; recurrent abscesses (skin, lymph nodes, liver), pneumonia, osteomyelitis; most common pathogens are S. aureus, Aspergillus and C. albicans, Nocardia and Salmonella. ▪ Granuloma formation (due to abnormal accumulation of ingested material) and inflammatory processes are the hallmark (pyloric outlet obstruction, bladder or ureteral obstruction, rectal fistulae or granulomatous colitis. ✓ Recurrent infections; multiple granulomatous lesions of the lungs, liver, lymph nodes, and gastrointestinal and genitourinary tracts; abscesses, Diagnosis: ▪ Flow cytometry using dihydrorhodamine 123 (DHR) to measure oxidant production (has taken the place of the NBT. Treatment: ▪ Only cure is stem cell transplant; otherwise supportive care including interferon to reduce serious infections. Chediak Higashi syndrome Definition: ▪ Impaired lysis of phagocytized bacteria, resulting in recurrent bacterial infection. Genetics: AR disorder Clinical findings: ▪ Recurrent infection, oculocutaneous albinism, hepatosplenomegaly, lymphadenopathy, pancytopenia, bleeding diathesis, and neurologic changes. Diagnosis: ▪ Neutropenia, giant granules in neutrophils. ▪ Genetic testing for LYST mutations can confirm the diagnosis. 384  Pediatrics (Immunology & Rheumatology) Evaluation of Suspected Immune Deficiency B-Cell T-Cell Complement Neutrophil Common Recurrent Opportunistic Pneumococci, Bacteria: organism bacterial: organisms: Neisseria. Staphylococci, Streptococci, CMV, Pseudomonas, Staphylococci, EBV, Serratia, Haemophilus, varicella, Klebsiella, Campylobacter; Candida, Salmonella; Viral: Pneumocystis jiroveci, Fungi: Enteroviruses; mycobacteriwa. Candida, Uncommon: Aspergillus. giardia, cryptosporidia. Age onset Age 5-7 months Usually age 2-6 Any age Early onset or later childhood months. to adult. Infections Most are Mucocutaneous Meningitis, Skin abscesses, recurrent candidiasis; arthritis, impetigo, sinopulmonary pulmonary and GI septicemia, cellulitis, infections and infections. recurrent suppurative recurrent sinopulmonary adenitis, enteroviral infections gingivitis, meningitis. oral ulcers, osteomyelitis, internal organ abscesses. Other Autoimmunity, Chronic diarrhea Autoimmune Prolonged findings lymphoreticular and failure to-thrive; disorders, attachment of malignancy post-vaccination vasculitis, umbilical cord, dissemination - glomerulonephritis poor wound varicella, BCG; , angioedema healing, hypocalcemia in decreased signs infancy; of infection graft- versus-host from transplacental maternal engraftment or nonirradiated blood 385  Pediatrics (Immunology & Rheumatology) Best Screen with IgA Lymphocyte count Screen is total Neutrophil initial test → if low, measure (low) hemolytic count IgG and IgM complement (quantitative (CH50) - will be immunoglobulins) depressed if any component is consumed Other Low antibody titers Best cost- effective Identify mode of Neutrophil Tests to specific antigens test for T-cell inheritance all are respiratory burst isohemmaglutinins, function Candida autosomal except after phorbol vaccines skin test for properdinester deficiency stimulation; (X-linked) most reliable now uses rhodamine fluorescence (replaced the NBT test) Specific Enumerate B-cells Flow cytometry Can easily Can identify tests with flow using monoclonal measure C3 and leukocyte cytometry antibodies C4 (hereditary adhesion (monoclonal recognizing T-cell angioedema); deficiencies with antibodies to B-cell CD antigens others require a flow cytometric specific CD (phytahemmaglutinin research lab assays antigens): B-cell , concanavalin A, of lymphocytes absent or present pokeweed mitogen) and neutrophils and number (CD18, CD11, CD15) *Note: For each, the most accurate test is molecular genetic diagnosis. 386  Pediatrics (Immunology & Rheumatology) Vasculitis Introduction: ▪ Vasculitis is defined as inflammation of blood vessels. ▪ It may result in vessel wall thickening, stenosis, and occlusion with subsequent ischemia and necrosis. ▪ Necrotizing inflammation can completely destroy segments of the wall and may lead to bleeding ▪ Vasculitis can involve any vessels and any organ system. The clinical presentation varies according to: ▪ The type of inflammation, ▪ The size, ▪ The distribution of the involved blood vessels. When to suspect vasculitis: ▪Unexplained systemic illness (no sepsis, no malignancy, no drugs). ▪Multiple organ involvement with no obvious cause ▪Symptoms of organ ischaemia ▪Other suggested features: - Palpable purpura - Glomerulonephritis (Haematuria) - Mononeuritis multiplex - Lung infiltrates. Classification ▪ Primary vs. secondary ▪ Size of predominant vessels involved - Large - Medium - Small and medium - Small ▪ ANCA positive/negative 387  Pediatrics (Immunology & Rheumatology) Primary Vasculitis Secondary Vasculitis 1. Large vessel vasculitis: ▪ Drugs (Amphetamin) ▪ Giant cell (Temporal) arteritis/(GCA) ▪ Infections (Meningeococcal septicemia) ▪ Takayasu’s arteritis ▪ Malignancies 2. Medium vessel vasculitis: ▪ Connective tissue diseases ▪ Polyarteritis Nodosa(PAN) ▪ Kawasaki’s disease 3. Small/ Medium vessel vasculitis: ▪ Wegener’s granulomatosis ▪ Churg-Strauss syndrome ▪ Microscopic polyangiitis 4. Small vessel vasculitis: ▪ Henoch Schonlein Purpura ▪ Essential mixed cryoglobulinaemia 5. Behçet's disease. 388  Pediatrics (Immunology & Rheumatology) Henoch-Schönlein purpura (HSP) Definition: ▪ Henoch-Schonlein Purpura (HSP) is an IgA vasculitis that presents with a purpuric rash affecting the lower limbs and buttocks in children. ▪ Inflammation occurs in the affected organs due to IgA deposits in the small blood vessels (arterioles and venules) of skin, joints, GI tract and kidney. ▪ Most common form of vasculitis of childhood ▪ A form of leucocytoclastic vasculitis of the small vessels (vascular damage from nuclear debris of infiltrating neutrophils) ▪ Often preceded by upper respiratory tract infection ▪ Genetic component suggested by occasional family clusters. Epidemiology: ▪ Worldwide distribution, ▪ All ethnic groups; ▪ Slightly greater in males; ▪ Almost all age 3-10 years; ▪ Occurs mostly in fall, winter and spring, many after a URI. Pathology: ▪ Infectious trigger is suspected, mediated by IgA and IgA-immune complexes ▪ Skin biopsy shows vasculitis of dermal capillaries and postcapillary venules with infiltrates of neutrophils and monocytes; in all tissues, immunofluorescence shows IgA deposition in walls of small vessels and smaller amounts of C3, fibrin and IgM. Clinical presentation: 1) Nonspecific constitutional findings. 2) Rash (100%): palpable purpura, start as pink macules and then become petechial and then purpuric or ecchymotic; usually symmetric and in gravity-dependent areas (legs and back of arms) and pressure points (buttocks); lesions evolve in crops over 3-10 days and may recur up to 4 months. Usually there is some amount of subcutaneous edema. 3) Arthralgia/arthritis (75%): oligoarticular, self-limited and in lower extremities; resolves in about 2 weeks, but may recur. 4) GIT: in up to 80%: pain, vomiting, diarrhea, ileus, melena, intussusception, mesenteric ischemia or perforation (purpura in GI tract). 5) Renal: up to 50%: hematuria (microscopic or macroscopic), proteinuria (If there is more than 2+ of protein on the urine dipstick the child has developed nephrotic syndrome and will have a degree of oedema.), hypertension, nephritis, nephrosis, acute or chronic renal failure. 6) Neurological: due to hypertension or CNS vasculitis, possible intracranial hemorrhage, seizures, headaches and behavioral changes. 7) Less common: orchitis, carditis, inflammatory eye disease, testicular torsion and pulmonary hemorrhage. 389  Pediatrics (Immunology & Rheumatology) American College of Rheumatology diagnosis: Need 2 of the following: (a) Palpable purpura (b) Age of onset