Rheumatology

1. Rheumatology

2. Henoch-schonlein purpura (HSP) or Anaphylactoid purpura It is a vasulitis of unknown etiology characterized by inflammation of small blood vessels with associated leukocytic infiltration of tissue, hemorrhage, and ischemia. It is the most common cause of nonthrombocytopenic purpura in the children. Etiology: The etiology is unknown, but the presence of immune complexes, which are predominantly composed of IgA, in association with HSP raising the suggestion that this illness may be allergy mediated. It also has been postulated that HSP is associated with group A streptococcal infection, but this also not proved.

3. Clinical features: HSP characterized by skin rash, arthritis, and gastrointestinal or renal vasculitis. 1. Skin rash: Is the hallmark of HSP which is consist of palpable purpura caused by small blood vessels inflammation in the skin leading to extravasation of blood into the surrounding tissue. IgA often is deposited in the lesions. The rash can occurs anywhere on the body, but it is classically found in dependent areas, on the buttock and lower extremities. The rash might associated with edema, particularly of the calves,dorsum of the feet, scalp, scrotum or labia. 2. Arthritis: Occurs in 80% of patients, it can affect any joint, but most commonly the ankles and knees. The arthritis is acute and can be painful with refusal to bear weight.

4. 3. GIT involvement: Occurs in about half of patients, presented as mild to moderate crampy abdominal pain due to small vessels involvement of GIT leading to ischemia. Less common manifestations are abdominal distention, bloody diarrhea, intussusceptions or abdominal perforation. GIT involvements typically occur during the acute phase of HSP and sometimes precede the onset of rash. 4. Renal involvement: Occurs in 1/3rd of patients which consist of acute GN manifested by hematuria, hypertension, or acute renal failure. Most cases of GN occur within the first few months of HSP, but rarely patients develop late renal disease which ultimately leads to chronic renal failure.

5. Investigations: 1. Raised ESR, CRP, and WBC counts as evidence of systemic inflammation. 2. Normal or even raised platlate counts, and this is the most important test to differentiate HSP from causes of thrombocytopenic purpura like SLE, ITP, or leukemia. 3. Urine test for hematuria, WBC casts, or proteinurea. 4. Blood urea and serum creatinine to evaluate renal function. 5. Stool test for presence of blood as evidence of GIT ischemia.

6. Differential diagnosis: 1. Idiopathic thrombocytopenic purpura (ITP). 2. Leukemia. 3. Systemic lupus erythematosus (SLE). 4. Serum sickness (e.g. drug-related). 5. Polyarteritis nodosa. 6. Juvenile rheumatoid arthritis. 7. Vasculitis associated with infections.

7. Treatment: A. Supportive treatment: include: 1. Adequate hydration. 2. Acetaminophen (paracetamol) or NSID for arthritis, edema, fever and malaise. 3. Avoidance of competitive activities. 4. Scrotal elevation and local cooling in presence of scrotal edema. B. Treatment of GIT manifestations (e.g. abdominal pain, hemorrhage, obstruction, and intussusceptions) by: 1. Oral or I.V. corticosteroids (prednisone) 1-2 mg/kg/day for 1-2 weeks followed by gradual tapering. 2. Barium enema reduction or surgical reduction or resection of intussusceptions. C. Treatment of renal involvement is same of the other forms of GN (corticosteroid and management of ARF).

8. Complications: 1. Development of nephritic syndrome. 2. Bowel perforation. 3. Testicular torsion due to scrotal edema. Prognosis: HSP is self limited vasculitis with excellent prognosis and most of children have complete resolution of the illness without any significant sequelae. Less than 1% of HSP patients might develop persistent renal disease.

9. Systemic Lupus Erythematosus (SLE) SLE is multisystemic disorder of unknown etiology characterized by the production of large amount of circulating antibodies (Abs) which form immune complexes trapped in the microvasculature, leading to inflammation and ischemia.

10. Clinical features: 1. Onset could be abrupt with fulminant disease or gradual. 2. Nonspecific symptoms include fatigue, malaise, low grade fever, and weight loss. 3. Cutanous manifestations: a- Malar "butterfly" rash: is raised erythematous rash on the cheeks or a cross the nasal bridge, on the forehead, or chin, it's improved with appropriate therapy. b- Photosensitivity, particularly during summer months, it's also improved with appropriate therapy. c- Discoid lupus: is an inflammatory process leads to disruption of the dermal-epidermal junction, resulting in permanent scarring and loss of pigmentation in the affected area. If it occurs in the scalp, result in alopecia due to loss of hair follicles. d- Raynaud phenomenon, which is not specific for SLE.

11. 4. Mouth and nasal sores resulting from mucosal ulceration are common findings which can lead to ulceration and perforation of the nasal septum. 5. LAP (particularly axillary) and splenomegaly due to reticuloendothelial system stimulation. 6. Serositis (pleuritis or pericarditis) causing chest pain with pleural or pericardial rubs or frank effusion. 7. Renal involvement: is one of the most serious manifestations of SLE and is common in pediatric SLE, occurring in 50-70% of children. Renal disease range from microscopic proteinurea or hematuria, to gross hematuriam nephretic syndrome, and renal failure. 8. Arthralgia and arthritis are common. The arthritis are rarely deforming (nonerosive arthritis) and typically involved the small joints of the hands, although any joint may be involved.

12. 9. Myalgia or frank myositis, with muscle weakness and muscle fatigability. 10. CNS manifestations: which could be subtle symptoms such as poor school performance and difficult concentration or serious manifestations such as seizures, psychosis, and stroke.

13. Investigations: A. Serological tests 1. Positive ANA founds in more than 97% of patients. 2. Positive antibodies to double-stranded DNA (anti-dsDNA) occurs in most patients. 3. Positive anti-smith Abs (anti-Sm). 4. Antiphospholipid Abs, its non specific and might found in many other rheumatological diseases and its presence might lead to increased risk of arterial and venous thrombosis which indicated by prolonged activated PTT. 5. Positive anticardiolipin Abs. 6. False-positive Venereal Disease Research Laboratory (VDRL) test.

14. B. Hematological abnormalities: 1. Leukopenia (particularly lymphopenia), thrombocytopenia, and anemia of chronic disease. 2. Coombs-positive autoimmune hemolytic anemia, manifested by presence of schistocytes and fragmented cells in blood film. 3. Low C3 and C4 levels due to consumption of complements proteins by excessive Abs and immune complexes production which could be return to normal levels by effective therapy of SLE. C. Urinary abnormalities: 1. Urinalysis shows hematuria and protein urea indicating lupus nephritis. 2. Serum BUN and createnin to evaluate renal function. 3. Hypoalbuminemia and hypoproteinemia may be present.

15. IV. Other tests: D. Other test 1. Elevated muscle enzymes in myositis. 2. Elevated CSF protein and elevated IgG-to-albumin ratio indicating Abs formation in CSF and help in diagnosis of CNS involvements. Diagnosis of SLE: The diagnosis of SLE must be established in the presence of 4 of following 11 diagnostic criteria which might be present at the same time or at different times during the course of illness. 1-malar rash fixed erythema over malar eminence 2-discoid rash erythematous raised patch 3-photosensitivity rash as result of usual reaction to sunlight 4-oral ulcer oral or nasopharyngeal painless ulcers 5-arthritis non erosive arthritis involving two or more peripheral joints

16. Diagnostic criteria of SLE: Physical signs: 6-serositis pleuritis or pericarditis 1. Malar (butterfly) rash. 2. Discoid lupus. 7. Seizures or psychosis in absence of metabolic toxins or drugs. 3. Photosensitivity. 4. Oral and nasopharyngeal ulcers. 6. Pleuritis or pericarditis (Serositis). 8. Renal disease (nephritis): proteinurea (>500mg/24 hr) or Cellular casts (RBC, granular, or tubular)

17. 9. Hematological disease: Hemolytic anemia with reticulocytopenia or Leukopenia (<4000 on 2 occasions) or Lymphopenia (<1500 0n 2 occasions) or Thrombocytopenia (<100,000/c.mm) 10. Positive anti-dsDNA or Positive anti-Sm or Evidence of presence of Antiphospholipid Abs IgG or IgM anticardiolipin Abs or Lupus anticoagulant or False-positive VDRL for >6 months. 11. Positive ANA in absence of drugs known to induce lupus.

18. Treatment of SLE: Treatment. 1- Corticosteroids are the mainstay of treatment for SLE, initially use pulse methylprednisolone and high dose of oral prednisone (2mg/kg) until induced remission of clinical manifestations, then followed by cautious tapering to reduce recurrence of symptoms. 2. NSAIDs used for treatment of arthralgia and arthritis. 3. Hydroxychloroquine for treatment of lupus skin disease, such as discoid lupus, and also as maintaince therapy of the disease to prolong period of remissions. 4. Cyclophosphamide effective in sever forms of lupus nephritis, with significant improvements and decreased rates of progression to renal failure, and in treatment of CNS lupus. 5. Steroid-sparing agents e.g. azothioprine and methotrexate indicated in patients who have relapse of clinical manifestations of SLE after tapering of corticosteroids therapy.

19. Long term complications of SLE: 1. Avascular necrosis due to corticosteroid therapy 2.infections 3.myocardial infarction 2. Infections. 3. Myocardial infarction. 4. Accelerated atherosclerosis during adult life. prognosis prognosis Prognosis: prognosis It is depend on the organ systems that are involved. Worse prognosis are seen in: 1. Sever lupus nephritis with risk of progression to renal failure. 2. Sever lupus cerbritis (CNS involvement) with risk of chronic disability. Thank you for your attention