CLINICAL TOPICS CONFERENCE Chapter 4, Immunopathology

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  1. Type I hypersensitivity reactions
  2. Type II hypersensitivity reactions
  3. Type III hypersensitivity reactions
  4. Type IV hypersensitivity reactions
  5. Acquired Immune Deficiency Syndrome (AIDS)

Case 1:

Clinical vignette 1

A 28 year-old female was driving on I-435 North on January 2, 1990. A passing motorist noticed her car go off the Kansas River bridge into the water. He stopped, dived into the freezing water, pulled her from the car, and began CPR. An ambulance soon arrived and continued resuscitative efforts. She was life-flighted to KUMC, where she was pronounced dead on arrival.

At autopsy, the patient's lungs were hyperinflated and showed marked mucus plugging. No water was found in her lungs. The prosector concluded that she was dead when she hit the water. An empty broncho-dilator inhalation device was found in her purse. Her mother later confirmed that she was having an acute asthma attack and was on her way to get her presciption refilled at her North Kansas City physician's office.

Discussion topics

  1. What is the clinical term for this type of asthma attack? What might have been some of the early symptoms? Late symptoms?

  2. Describe the pathogenic events, in sequence, that lead to this woman's death.

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Case 2:

Clinical vignette 2

An obese, 38-year-old woman noted swelling of the neck 3 months before admission. She complained of easy fatigability, slight difficulty swallowing and cold intolerance. Deep tendon reflexes were depressed. Her mother had a history of goiter.

Upon physical examination, her blood pressure was 146/80, pulse 80/min. and temperature 37oC. The thyroid was diffusely enlarged without nodularity. There was no exophthalmos or lid-lag. The skin and hair were normal. The initial clinical impression was "goiter".

Laboratory examination revealed a decreased T4 , with thyroid stimulating hormone (TSH) increased. A thyroidectomy was performed. The surgical pathologist received a 4 x 2 x 2.4 cm. segment of thyroid weighing 22 grams. The parenchyma was tan and fleshy, with the consistency and general appearance of a lymph node. The pathologic diagnosis was Hashimoto thyroiditis.

Discussion topics

  1. Describe the pathogenic events, in sequence, leading up to this patient's surgery. How do they account for the patient's symptoms?

  2. Is complement involved in the destruction of the gland? If not, how is the thyroid destroyed?

  3. What other autoimmune diseases may be associated with Hashimoto thyroiditis? What do you think of the patient's mother having a history of goiter?

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Case 3:

Clinical vignette 3

A 24-year-old women's illness began one year before death, with weight loss and fatigue. About 7 months later a red rash appeared over the bridge of her nose and the exposed areas of the skin. This was followed in two days by joint pains. All symptoms were intensified by sun exposure. About a month later, enlarged lymph nodes and a sore tongue appeared and, a month after this, chills, fever, nausea and vomiting.

One month later, or 2 months before death, the patient was admitted to the hospital for the first time.

Upon presentation, her skin rash was generalized, purple and mottled. Hemorrhages were present in the sclera and gums. Her blood pressure was 110/75, and her temperature was 40o C. Laboratory examinations revealed leukopenia, with 3,400 white blood cells per cubic mm., anemia with 12.5 gm hemoglobin and 3.8 million red blood cells per cubic mm, hematuria, and 3+ albuminuria. Treatment with penicillin produced some improvement, and the patient was discharged from the hospital.

She was re-admitted 12 days before death with recurrence of all previous signs and symptoms. In addition, there was swelling of the popliteal spaces, and an electrocardiogram showed evidence of carditis. Leukopenia was now severe, WBC were 1,200 per cu. mm., of which 66% were segmented neutrophils and 19% stab forms.

Topics for discussion

  1. What is the major immunologic mechanism involved in this patient's kidney disease? In her hematologic disease?

  2. What antibodies and antigens are in the immune complexes which precipitated in the kidneys?

  3. Why did sun exposure make this patient's symptoms worse?

References

  1. Systemic Lupus Erythmatosus at the National Jewish Hospital, Denver, CO, 1992.

  2. Lupus Society - A patient advocacy group.

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Case 4:

Clinical vignette 4

The patient was a 24 year old female medical student from Peru. She had received a tuberculosis vaccination with
BCG vaccine as a child. Upon entering the University of Kansas School of Medicine, she was told she had to take a skin test with the purified protein derivative (PPD). She tried to refuse, but was told it was a requirement. She allowed the nurse to administer the test. Upon examination 3 days later, she had a half-dollar sized, indurated lesion on her forearm. The skin had begun to slough.

Discussion topics

  1. How is a type IV hypersensitivity reaction (and by extension, granuloma formation) fundamentally different from all other types of immunologic tissue injury?

  2. Describe what BCG is and why it is commonly administered in some countries. Why is it not utilized in the US ?

  3. What should have been done instead of administering the PPD to this student?

References

  1. MMWR 37: 663-664, 669-675, 1988. CDC Prevention Guidelines: Use of BCG vaccines in the control of tuberculosis.

  2. MMWR 39 (RR-8), 1990. Screening for tuberculosis and tuberculous infection in high-risk populations.

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Case 5:

Clinical vignette 5

A 26-year-old white male consulted his physician because of a persistent sore throat. Examination revealed oral candidiasis. Further questioning disclosed that the patient had experienced lethargy, fevers, and a 40 lb weight loss in the preceding four months. He gave a history of numerous homosexual contacts since age 18. A test for antibody to HIV was positive, and the absolute number of CD-4 cells, determined by flow cytometry, was 200 per microliter.

The patient lived for approximately six months, and was hospitalized five times. Pneumonia was diagnosed on his first hospitalization; cytomegalovirus was cultured from bronchoscopy specimens, and Pneumocystis cariniiwas simultaneously identified cytologically. He was successfully treated with trimethoprim/sulfa for pneumocystosis, but two months later developed recurrent pulmonary infiltrates. Culture of specimens obtained by bronchoscopy then grew Mycobacterium avium intracellulare (MAI). The CD-4 count at that time was <10 per microliter. He was treated with isoniazid, ethambutol and rifampin, but multiple sputum and blood cultures continued to be positive for MAI. His anti-mycobacterial chemotherapy was changed to ansamycin, which also failed to eradicate the organism.

The patient was anorectic and weighed less than 120 lbs at his death. He ultimately died of respiratory failure; at his request, no resuscitative efforts were undertaken.

Discussion topics

  1. What effects on immunity are exerted by the HIV? How did they manifest in this patient?

  2. How does the absolute CD-4 count affect your differential diagnosis of possible infectious/neoplastic processes in an AIDS patient?

References

  1. MMWR 44, RR8, July 1995. Guidelines for the prevention of opportunistic infections in persons infected with HIV: A summary.

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