23. A 23-year-old man presented with fever and sore throat; physical examination revealed an erythematous oropharynx and cervical lymphadenopathy. The patient had no known history of drug allergy. He was started on an empirical regimen of amoxicillin for streptococcal pharyngitis. Three days later, he returned to your office complaining that his symptoms had continued and that he had developed a rash.
An erythematous maculopapular rash was noted on physical examination. A monospot test was per-formed. The results come back positive.
Which of the following statements regarding this patient’s exanthematous drug eruption is true?
❑ A. Persistence of fever is not helpful in determining whether the symp-toms are the result of an allergic reaction, because fever is common in simple exanthematous eruptions
❑ B. Systemic corticosteroids are always required to treat this drug eruption
❑ C. After the patient’s infectious process resolves, he will be able to tolerate all β-lactam antibiotics, including ampicillin
❑ D. In patients with viral infections, the mechanism of exanthematous eruption caused by ampicillin is IgE-mediated mast cell degranulation
❑ E. This patient’s rash can be expected to progress to a vesicular stage before resolution
Key Concept/Objective: To understand that ampicillin-amoxicillin–related exanthematous erup-tions that occur in patients with viral infecerup-tions do not appear to be IgE-mediated and that patients can tolerate penicillins and cephalosporins once the infection resolves
The etiology of the ampicillin rash that occurs in association with a viral infection is unknown, but the rash does not appear to be IgE-mediated. Patients can tolerate all β-lac-tam antibiotics, including ampicillin, once the infectious process has resolved. Fever is not associated with simple exanthematous eruptions. These eruptions usually occur within 1 week after the beginning of therapy and generally resolve within 7 to 14 days. The exan-them’s turning from bright red to brownish red marks resolution. Resolution may be fol-lowed by scaling or desquamation. The treatment of simple exanthematous eruptions is generally supportive. For example, oral antihistamines used in conjunction with soothing baths may help relieve pruritus. Topical corticosteroids are indicated when antihistamines do not provide relief. Systemic corticosteroids are used only in severe cases.
Discontinuance of the offending agent is recommended. (Answer: C—After the patient’s infec-tious process resolves, he will be able to tolerate all β-lactam antibiotics, including ampicillin)
24. A 35-year-old woman with HIV was recently started on trimethoprim-sulfamethoxazole for Pneumocystis carinii prophylaxis. She now presents with fever, sore throat, malaise, and a desquamating rash on her trunk. Laboratory studies are notable for the following abnormalities: serum creatinine, 2.1 mg/dl; aspar-tate transaminase (AST), 215 mg/dl; and alanine transaminase (ALT), 222 mg/dl.
Which of the following statements regarding the care of this patient is true?
❑ A. She may become hypothyroid as a result of the development of autoimmune thyroiditis within 2 months after the initiation of symp-toms
❑ B. In the future, she should avoid sulfonylureas, thiazide diuretics, furosemide, and acetazolamide
❑ C. An elevated serum IgE level confirms the diagnosis of hypersensitivity syndrome reaction
❑ D. Her first-degree relatives have the same risk of experiencing a hyper-sensitivity syndrome reaction as the general population
Key Concept/Objective: To understand the basic pathophysiology, epidemiology, and clinical manifestations of hypersensitivity drug reactions
Sulfonamide antibiotics can cause hypersensitivity syndrome reactions in susceptible per-sons. This kind of adverse drug reaction is caused by the accumulation of toxic metabo-lites; it is not the result of an IgE-mediated reaction. The primary metabolic pathway for sulfonamides involves acetylation of the drug to a nontoxic metabolite and renal excre-tion. An alternative metabolic pathway, quantitatively more important in patients who are slow acetylators, engages the cytochrome P-450 mixed-function oxidase system. These enzymes transform the parent compound to reactive metabolites—namely, hydroxy-lamines and nitroso compounds, which produce cytotoxicity independently of preformed drug-specific antibody. In most people, detoxification of the metabolite occurs. However, hypersensitivity syndrome reactions may occur in patients who are unable to detoxify this metabolite (e.g., those who are glutathione deficient). Other aromatic amines, such as pro-cainamide, dapsone, and acebutolol, are also metabolized to chemically reactive com-pounds. The risk of first-degree relatives’ developing hypersensitivity reactions to sulfon-amides is higher than in the general population. Cross-reactivity should not occur between sulfonamides and drugs that are not aromatic amines (e.g., sulfonylureas, thiazide diuret-ics, furosemide, and acetazolamide); therefore, these drugs can be safely used in the future.
Most systemic manifestations of the hypersensitivity reaction syndrome occur at the time
of skin manifestations. However, a subgroup of patients may become hypothyroid as part of an autoimmune thyroiditis up to 2 months after the initiation of symptoms. (Answer:
A—She may become hypothyroid as a result of the development of autoimmune thyroiditis within 2 months after the initiation of symptoms)
25. A 19-year-old female college student is taking ampicillin and clavulanate for pharyngitis. After 5 days of treatment, she develops a generalized erythematous maculopapular rash. She is given a monospot test, and the result is positive.
For this patient, which of the following statements is true?
❑ A. Exanthematous rashes may occur in up to 80% of patients with infec-tious mononucleosis that is treated with ampicillin
❑ B. The patient should undergo skin testing with penicilloyl polylysine and graded desensitization before any treatment with penicillins
❑ C. Treatment should include changing to a macrolide antibiotic
❑ D. The patient is experiencing a type II, or cytotoxic, hypersensitivity reaction
❑ E. The rash will worsen until ampicillin is stopped
Key Concept/Objective: To be able to recognize typical ampicillin rash
The causal mechanism of an exanthematous ampicillin rash in the setting of a concurrent viral illness is unclear. It does not appear to be mediated by IgE, so β-lactams can be toler-ated and sensitivity testing is not warranted. Although stopping ampicillin is suggested, the rash will generally resolve even if ampicillin is continued. (Answer: A—Exanthematous rashes may occur in up to 80% of patients with infectious mononucleosis that is treated with ampicillin)
26. In contrast to exanthematous rashes, which of the following is true of urticaria that develops after drug exposure?
❑ A. Type I immediate hyersensitivity reactions cause all urticarial rashes
❑ B. In severe reactions with angioedema and bronchospasm, plasmaphere-sis should be initiated early in treatment
❑ C. Urticarial rashes remain fixed for up to several days and may recur in the same location with repeated exposure to the causative drug
❑ D. Because of the risk of severe reactions, patients with drug-induced urticaria should not undergo skin testing or desensitization
❑ E. Biopsy should be considered for urticarial lesions that persist for longer than 24 hours
Key Concept/Objective: To know the complications associated with urticarial rashes
For lesions that persist for longer than 24 hours, consideration should be given to the use of biopsy to exclude vasculitis. Biopsy may show deposits of IgM and C3 immune com-plexes within the lesions. Besides being associated with type I reactions, urticaria may occur with type III hypersensitivity reactions and as a result of nonimmunologic release of histamine caused by certain drugs, such as morphine. Treatment of severe allergic reac-tions includes epinephrine, antihistamines, bronchodilators, corticosteroids, and support-ive treatment with fluids and pressors if needed. Patients can be desensitized if there is no therapeutic alternative to the causative drug. (Answer: E—Biopsy should be considered for urticar-ial lesions that persist for longer than 24 hours)
27. A 55-year-old woman has a well-demarcated reddish brown macular rash on her arm. The lesion recurs periodically and resolves slowly, with some persisting hyperpigmentation. She is otherwise healthy and takes no medications except an occasional laxative.
Which of the following is the most likely diagnosis for this patient?
❑ A. Urticaria
❑ B. Lichen planus
❑ C. Pemphigus
❑ D. Fixed drug eruption
❑ E. Contact dermatitis
Key Concept/Objective: To be able to diagnose fixed drug eruption in the appropriate setting
Fixed drug eruptions may occur after ingestion of several over-the-counter medications, including phenolphthalein laxatives and ibuprofen. After an exacerbation, a refractory period may occur during which reexposure does not produce a recurrence of the rash, so the diagnosis may be elusive. The most common site of involvement is the genitalia, so fixed drug eruptions must be distinguished from various sexually transmittable afflictions.
(Answer: D—Fixed drug eruption)
28. Which of the following is true concerning the development of cutaneous necrosis in a patient taking warfarin?
❑ A. Skin lesions appear weeks to months after beginning treatment
❑ B. The pretibial area is the most common site
❑ C. Lesions generally occur only when the INR exceeds 3.5
❑ D. Treatment includes heparinization
❑ E. Patients with lupus anticoagulant or antithrombin III deficiency are predisposed
Key Concept/Objective: To understand the pathogenesis and treatment of warfarin-induced skin necrosis
Patients with protein C or protein S deficiency may be predisposed to develop warfarin-induced skin necrosis. They develop a paradoxical hypercoagulable state at the onset of treatment because of suppression of protein C anticoagulant activity, resulting in venous thrombosis and necrosis 3 to 5 days later. Fatty areas are most frequently affected. Heparin, vitamin K, and fresh frozen plasma are the mainstays of treatment. (Answer: D—Treatment includes heparinization)
29. One month after starting phenytoin after a head injury, a 24-year-old man developed a low-grade fever, cervical lymphadenopathy, and a generalized erythematous maculopapular rash with subsequent exfo-liation in some areas.
Which of the following statements is true of this condition?
❑ A. It is commonly associated with penicillins and ACE inhibitors
❑ B. Limited laboratory investigation consisting of a complete blood count and a urinalysis is warranted
❑ C. Graves disease is a late complication
❑ D. First-degree relatives of the patient are at increased risk for similar reactions
❑ E. After the cutaneous reactions, rechallenge and desensitization are advised before reinstituting therapy
Key Concept/Objective: To be able to recognize the signs and complications of hypersensitivity syndrome
Hypersensitivity syndrome is a potentially serious reaction occurring from 1 week to sev-eral weeks after exposure to aromatic anticonvulsants (e.g., phenytoin, carbamazepine),
sulfonamides, or other drugs with an aromatic amine chemical structure (procainamide).
Inheritable defects in the metabolic pathways for these agents may place close relatives at increased risk as well. Eosinophilia, hepatitis, and interstitial nephritis may be detected initially, and autoimmune thyroiditis can cause late hypothyroidism. The rash may range from an exanthem to severe Stevens-Johnson syndrome or toxic epidermal necrolysis.
Because these reactions are severe (and not IgE-mediated), patients and family members are advised to avoid the causative drug and drugs that are chemically similar to it. (Answer:
D—First-degree relatives of the patient are at increased risk for similar reactions)
For more information, see Shear NH, Knowles S, Shapiro L: 2 Dermatology: VI Cutaneous Adverse Reactions. ACP Medicine Online (www.acpmedicine.com). Dale DC, Federman DD, Eds. WebMD Inc., New York, March 2004