questions_ Immunology & Allergy

Educational objective: Emphasize angioedema as an important side effect of ACE inhibitor therapy.

Angiotensin converting enzyme (kininase II) promotes degradation of angiotensin II, but also the degradation of bradykinin. Therapy with angiotensin converting enzyme (ACE) inhibitor results in decreased levels of angiotensin II and increased levels of bradykinin. This may result in angioedema. This mechanism is equal for all ACE inhibitors, and all of them are known to cause angioedema (0.1-0.7% of patients treated). Since large numbers of patients are treated with ACE inhibitors (especially hypertensive diabetic patients), this is a common cause of angioedema seen in emergency rooms. The main distinguishing feature of ACE inhibitor-induced angioedema is the older age of patients and absence of any allergic history.

In this patient there are also normal results of the complement components measurements (including C1-INH-functional/antigenic), which virtually exclude hereditary or acquired angioneurotic edema due to C1 inhibitor deficiency. There is no history of allergy, and no exposure to any substance that is known to cause anaphylaxis in this patient. Although about 15% of patients with hypereosinophilic syndrome exhibit angioedema, in this patient all routine laboratory results were within normal limits, thus excluding hypereosinophillia.

Ref. Clifton OB III. Angioedema, Up To Date - Version 8.1 February 2000.

Educational objective: Review most common insects causing local reactions after a sting in the U.S.A.

Insect stings may cause systemic reactions that may be fatal (Approximately 40 deaths are reported in the U.S.A. per year), but most commonly they cause local reactions. Insects responsible for most of the allergic reactions that are clinically significant are honey bees, hornets, yellow jackets, and wasps. These all belong to Hymenoptera order.

In addition, stings may be caused by harvester ants and fire ants. Rare causes of allergic reactions in humans are bumblebees and sweat bees. Africanized honey bees have migrated to the U.S.A. through Texas and have been known to produce massive (but rarely fatal) stinging incidents, thus earning the nickname “Killer bee”.

Scorpion stings consist of envenomation with toxin containing a neurotoxin that causes immediate burning with severe pain and swelling, but are rare and only found in southern states and in California.

Educational objective: Review important features of aspirin sensitivity.

Nonsteroidal anti-inflammatory medications (including the aspirin and indomethacin) may cause two types of allergic-like symptoms in some individuals. About 1% of all persons experience urticaria/angioedema and about one half of a percent will experience rhinosinusitis and asthma-like symptoms. Asthma-like symptoms develop rapidly after ingestion of offending substance (within 1 hour), while urticaria/angioedema may develop up to 24 hours after ingestion.

In patients with known sensitivity to nonsteroidal anti-inflammatory medications it is safe to use acetaminophen.

Patients with bacterial endocarditis may develop the following forms of renal disease: renal embolic disease, post-infectious immune complex-mediated glomerulonephritis, and drug-induced acute interstitial nephritis.

Renal embolism is suggested if there is acute, most commonly unilateral flank pain even several months after bacteriologic cure of the endocarditis. This condition may be demonstrated by perfusion defect on renal radionuclide scan, and may be associated with other embolic phenomena.

Immune complex-mediated glomerulonephritis has clinical manifestations similar to other forms of acute glomerulonephritis, hematuria, red cell and other cellular casts in association with varying degrees of hypertension and renal insufficiency. Nephrotic syndrome is unusual.

The interstitial nephritis shares many of the clinical findings of the glomerulonephritis, hematuria, mild proteinuria and renal insufficiency, but no red blood cell casts. The distinction also may be made based on the timing of the renal insufficiency development. Glomerular disease usually peaks just before the institution of appropriate antibiotic therapy, while acute interstitial nephritis occurs after institution of antibiotic therapy, requiring ten or more days of treatment. It is also associated with fever, eosinophilia and eosinophiluria

Educational objective: Differentiate between different causes of proximal muscle weakness. Polymyositis is a disease of inflammatory nature affecting most commonly the proximal muscles of the upper and lower extremities. Unlike myasthenia gravis and Eaton-Lambert syndrome there is no involvement of the ocular muscles, and there is no loss of the muscle power with repetition of the movement (Myasthenia gravis and Eaton-Lambert syndrome are associated with worsening symptoms as the day progresses). Hyperthyroidism is associated with development of proximal muscle weakness, but this is usually associated with other symptoms of hyperthyroidism (weight loss, temperature intolerance, palpitations, diarrhea, etc.). In addition, onset and progression are usually more gradual. Muscular dystrophies are disorders that are relatively rare, most of them manifest itself early in life, and most of them are slowly progressive. These features make this diagnosis unlikely in this patient.

Educational objective: Differentiate between different causes of proximal muscle weakness. Polymyositis is a disease of inflammatory nature affecting most commonly the proximal muscles of the upper and lower extremities. Unlike myasthenia gravis and Eaton-Lambert syndrome there is no involvement of the ocular muscles, and there is no loss of the muscle power with repetition of the movement (Myasthenia gravis and Eaton-Lambert syndrome are associated with worsening symptoms as the day progresses).

Hyperthyroidism is associated with development of proximal muscle weakness, but this is usually associated with other symptoms of hyperthyroidism (weight loss, temperature intolerance, palpitations, diarrhea, etc.). In addition, onset and progression are usually more gradual. Muscular dystrophies are disorders that are relatively rare, most of them manifest itself early in life, and most of them are slowly progressive. These features make this diagnosis unlikely in this patient.

Educational objective: Review best diagnostic modalities for diagnosis of polymyositis.

Polymyositis is an inflammatory disorder usually affecting proximal muscles of the upper and lower extremities. It can be associated with malignancies and with skin rash (dermatomyositis). Diagnosis is best confirmed by muscle biopsy. Findings characteristic of the disease include intense inflammatory reaction (infiltration with mononuclear cells) and widespread destruction of the muscle fibers. Associated laboratory findings are not diagnostic but are supportive of diagnosis and include elevated levels of the serum creatine phosphokinase, aldolase, ALT and LDH. Erythrocyte sedimentation rate is commonly elevated. Electromyographic results are abnormal, too.

Educational objective: review important features of Henoch-Schönlein purpura.

This is a classical presentation of hypersensitivity vasculitis (purpura Henoch-Schönlein). The pathohistologic hallmark of the disease is small vessel vasculitis (especially postcapillary venules). Vasculitis is leukocytoclastic. Later in the course of disease mononuclear cells predominate. Disease is caused by immune complexes deposition that contains IgA antibodies. Disease is usually self-limited but chronic cases have been described. Immune complex deposition affects skin, gastrointestinal tract and kidneys.

Educational objective: Review features of Felty’s syndrome.

This patient most likely suffers from Felty’s syndrome, a condition which consists of chronic rheumatoid arthritis, splenomegaly, neutropenia and in some cases anemia and thrombocytopenia. These patients usually have high titers of rheumatoid factor and subcutaneous nodules. The syndrome is very uncommon in African-American patients. Patients have increased risk for infections because of low number of leucocytes but also because of their dysfunction. It was thought that hypersplenism was responsible for neutropenia, but splenomegaly is not consistently found in all patients and splenectomy fails to correct neutropenia in all patients.

Educational objective: Review features of Stevens-Johnson syndrome.

This patient presents with a syndrome highly suggestive of Stevens-Johnson syndrome, a blistering disorder that is similar but more severe than erythema multiforme. Presentation includes multiple erosions of mucosal membranes. Multiple small blisters on dusky or purpuric macules and atypical target lesions also characterize this disorder. Systemic symptoms include malaise and fever. These lesions usually affect less than 10% of the body surface. Stevens-Johnson syndrome can be caused by many medications, including phenytoin, phenobarbital, penicillin, sulfonamides, phenothiazines, quinidine and salicylates. Patients with seizure disorders are particularly prone to Stevens-Johnson syndrome. There are descriptions of cases caused by viral infections and Mycoplasma, but these are rare.

Educational objective: Review features of Pityriasis rosea.

This is most likely Pityriasis rosea, a disorder characterized by a single initial lesion (herald patch) which is usually located on the trunk and often mistaken for tinea corporis (ringworm). Careful examination of the lesion reveals that scaly ring does not reach the edge of the lesion (erythematous border), as is the case with ringworm. In addition, the pityriasis rosea herald patch is followed in one to two weeks by generalized eruption of red plaques that follow the skin lines and may resemble a Christmas tree.

Educational objective: Emphasize association of rheumatoid arthritis with HLA-DR4 genotype.

This patient has disease highly likely to be rheumatoid arthritis (RA). Therefore, she will very likely have elevated erythrocyte sedimentation rate. Many of them will be positive for rheumatoid factor (autoantibody), and a somewhat lesser number will be positive for antinuclear antibody.

In addition, she has about a 70% chance to be carrying HLA-DR4 antigen. This form of major histocompatibility complex antigen is highly associated with RA in several populations (although there are some groups in which there is no such association, but rather with HLA-DR1 and HLA-Dw16). A common feature of all these molecules is identical amino acids at positions 67-74 in third hypervariable region on â-chain.

There is no association of RA with HLA-DR2.