Serum sickness

The case presentation of Gregory Barens

1. Case presentation of Gregory barens by N athiya Gregory brought to children’s hospital , with HIGH FEVER COUGH DYSPNEA

2. On physical examination , he was pale , looked dehydrated , breathing rapidly with flaring nostrils. Respiratory rate : 62/min (normal :20/min) Pulse :120/min (normal : 60-80/min) Blood pressure :90/60mmHg (normal ) Auscultation : crackles on lower left lobe of left lung Diagnosis : LOBAR PNEUMONIA

3. Laboratory Results : WBC count – 19000 cells (normal-4000-7000 cells) 87% neutrophils (normal -60%) Infection with gram positive cocci : streptococcus pneumoniae No history of allergy to penicillin Treatment: Intravenous ampicillin (1g every 6 hours) 4 th day – RS 40/min ; WBC count 9000 ; temp 37.5 C 9 th day – no fever ; WBC count 7000

4. When ampicillin was replaced by penicillin , Symptoms like Puffy eyes Large hives(urticaria) on abdomen Anti histamine Benadryl was given orally& penicillin was discontinued Two hours later wheezing was heard all over lungs which responded to inhalation of beta2-adrenergic agent albuterol He also had reddened eyes owing to inflamed conjunctiva Swelling around mouth

5. Lymph nodes (cervical , axillary , inguinal) and spleen – enlarged Ankles and knee joints – swollen & painful Raised WBC with predominant lymphocytes (72%) Plasma cells were detected in blood smear RBC sedimentation rate 30mm/h Serum C1q & C3 levels DIAGNOSIS : SERUM SICKNESS & given BENADRYL and NAPROSYN (a non-steroidal anti-inflammatory agent)

6. Rash and swellings became worse Purpuric lesions on feet No blood in stool Later Gregory became agitated , disoriented , couldn’t recognize his parents Examination of CSF : presence of inflammatory cells Increased protein concentration EEG: circulation of blood in posterior part of brain Biopsy of purpura : moderate edema & IgG and C3 deposition

7. TYPE III HYPERSENSITIVITY Type III hypersensitivity  occurs when there is accumulation of immune complexes (antigen-antibody complexes) that have not been adequately cleared by innate immune cells, giving rise to an inflammatory response and attraction of leukocytes. Such reactions progressing to the point of disease produce  immune complex diseases .

8. Serum sickness When an antigen is injected intravenously , the immune complexes formed can be deposited at various sites When deposited in The synovial tissue inflammation of joints Arthritis The kidney glomeruli glomerulonephritis The endothelium of blood vessels vasculitis

9. Serum from the blood of immunized animals contained ANTITOXIN

10. Although horse serum is no longer used , other foreign proteins are still administered to the patients The most common cause of serum sickness is antibiotics esp. penicillin and its derivatives , which act as HAPTENS These drugs bind to proteins ( CARRIERS ) elicit rapid and strong IgG antibody response Antigen may be exogenous or endogenous

11. Symptoms of serum sickness can include: Fever. General ill feeling. Hives. Itching. Joint pain. Rash. Swollen lymph nodes.

12. Urticaria , is a prominent feature of the rash, implying a role for histamine derived from mast-cell degranulation. The mast-cell degranulation is triggered by the ligation of cell surface FcγRIII by IgG-containing immune complexes. Serum sickness after a second dose of antigen follows the kinetics of a secondary antibody response and the onset of disease occurs typically within a day or two. Serum sickness is nowadays seen after the use of anti-lymphocyte globulin , employed as an immunosuppressive agent in transplant recipients, & also, rarely, after the administration of streptokinase, a bacterial enzyme that is used as a thrombolytic agent to treat patients with a myocardial infarction or heart attack.

13. Immune complexes in blood vessels

14. Two reasons why small immune complexes would be cleared more slowly than large complexes Small complexes activate complement less effectively than large complexes because C1 must bind to several Fc regions before it is activated. The avidity of complexes for binding to phagocytes will also be increased when several Fc regions are available to bind to the Fc receptors on a phagocyte. If this were not so, monomeric antibody would block binding of complexes to Fc receptors. The formation of complexes is followed by an abrupt fall in total hemolytic complement. The clinical signs of serum sickness that develop are due to granular deposits of antigen–antibody and C3 forming along the glomerular basement membrane (GBM) and in small vessels elsewhere. As more antibody is formed and the reaction moves into antibody excess, the size of the complexes increases and they are cleared more efficiently.

15. Treatment: He was started on anti-inflammatory corticosteroid prednisone Symptoms improved progressively Joint swelling and splenomegaly resolved He was discharged after 7 days of onset of serum sickness on a slowly decreasing course of prednisone and Benadryl He had no IgE antibodies against penicillin or ampicillin detected by both immediate hypersensitivity skin test and RAST Instruction: Gregory should never be given penicillin, penicillin derivatives or cephalosporins