The following cases and commentary, which involve dermatology, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).
Case 1: Widespread skin blistering
A 24-year-old woman is evaluated in the emergency department for skin blistering. Her symptoms began 3 days ago when she noted a gritty sensation in her eyes; the following day her skin all over her body became red and painful. When she awoke today, her skin was blistered and there were moist, open erosions where the skin had sloughed off. Approximately 1 week ago, she received a 3-day course of trimethoprim-sulfamethoxazole for an uncomplicated urinary tract infection. She has a history of gastroesophageal reflux disease, which is treated with omeprazole that was started 1 year ago. She also takes ibuprofen intermittently for pain.
On physical examination, temperature is 39.1°C (102.4°F), blood pressure is 110/75 mm Hg, pulse rate is 105/min, and respiration rate is 20/min. There is confluent erythema of the entire trunk and all extremities, with blistering and erosions affecting greater than 30% of the body surface area. Lateral pressure on erythematous, nonblistered skin causes the skin to slough. Erosions are present on the eyelids, and there is conjunctival hyperemia. The lips are crusted and bloody, and there are ragged ulcers on the buccal mucosa. There are painful ulcers on the labia minora. Laboratory studies show a slight elevation in the leukocyte count with increased polymorphonuclear cells and eosinophils, normal renal function, and a slight elevation in liver aminotransferase levels.
Which of the following is the most appropriate first step in management?
A. Empiric acyclovir
B. Empiric ceftazidime and vancomycin
C. Systemic corticosteroids
D. Stop all medications
Case 2: Painful rash with fever
A 64-year-old man is evaluated in the emergency department for a rash that first developed 3 days ago and has rapidly spread to cover most of his body. His skin is painful and does not itch. He feels feverish and ill. He has a history of mild psoriasis, hypertension, asthma, and prostate cancer. His psoriasis has been well controlled with topical corticosteroids as needed. His prostate cancer was treated with radiation therapy 6 years ago and is in remission. His medications include lisinopril (started 3 weeks ago), an inhaled corticosteroid and salmeterol daily, and inhaled albuterol as needed. One week ago, he completed a 10-day tapering dose of oral corticosteroids for an acute exacerbation of asthma. He reports no known medication allergies.
On physical examination, he appears ill. Temperature is 38.9°C (102.0°F), blood pressure is 118/78 mm Hg, and pulse rate is 112/min. Greater than 90% of his body surface area is erythematous. There are widespread coalescing erythematous patches and plaques, many with pinpoint pustules coalescing into lakes of pus and many with fine desquamation. Erythematous plaques with overlying silvery scale are present on his occipital scalp. His conjunctival, oral, and urethral mucous membranes are normal. There is no palpable lymphadenopathy. A complete blood count reveals leukocytosis with a predominance of polymorphonuclear cells. A complete metabolic profile and serum aminotransferase levels are normal.
Which of the following is the most likely diagnosis?
A. Drug hypersensitivity syndrome
B. Paraneoplastic erythroderma
C. Pustular psoriasis
D. Sézary syndrome (cutaneous T-cell lymphoma)
E. Staphylococcal scalded skin syndrome
Case 3: Recurrent shingles and weight loss
A 37-year-old man is evaluated for a 6-day history of a painful eruption on his left posterior thorax. He had an episode of shingles 1 year ago that was treated with famciclovir. He has a history of alcoholism and intermittent injection drug use. He has lost approximately 3.0 kg (6.6 lb) over the past 3 months. He has had increased fatigue but denies fever, chills, lymphadenopathy, jaundice, or change in his bowel habits. He takes no medications.
On physical examination, temperature is 37.0°C (98.6°F), and BMI is 28. The skin findings are shown.
Oral mucous membranes are normal. There is no jaundice, lymphadenopathy, or hepatosplenomegaly. Direct fluorescent antibody test is positive for varicella-zoster virus.
Which of the following is the most likely underlying disease?
B. Diabetes mellitus
C. Hepatitis B
D. Hepatitis C
E. HIV infection
Case 4: Acute rash on the face and eye
A 35-year-old man is evaluated for an acute rash on his face. The rash is painful and somewhat itchy, and his left eye is swelling shut. He has a history of long-standing atopic dermatitis, which has been reasonably well controlled with regular use of emollients and topical corticosteroids. His current medications are triamcinolone ointment, tacrolimus ointment, and hydroxyzine. He has lately been lax in using his medications because of recent travel and therefore has been scratching more. He is allergic to sulfa.
On physical examination, vital signs are normal. The skin findings of the affected eye are shown.
The conjunctivae are inflamed, but no purulence is noted. No gross abnormalities of the cornea are visible. Skin findings on the trunk and arm are shown.
The left preauricular lymph nodes are slightly enlarged and tender.
Which of the following is the most likely diagnosis?
A. Acute allergic contact dermatitis
B. Acute atopic dermatitis
C. Eczema herpeticum
D. Staphylococcus aureus pyoderma
Case 5: Rash after MRSA infection
A 28-year-old man is evaluated in the emergency department for an 8-hour history of fever, malaise, and a rash on his shoulders, lower back, arms, and palms. Ten days ago he was started on oral trimethoprim-sulfamethoxazole therapy for methicillin-resistant Staphylococcus aureus infection. His last dose of trimethoprim-sulfamethoxazole was taken this morning. He takes no other medications and has no known allergies.
On physical examination, temperature is 38.6°C (101.4°F), blood pressure is 110/70 mm Hg, pulse rate is 110/min, and respiration rate is 20/min. There are erythematous, urticarial, targetoid plaques on the shoulders that are studded with small, tense blisters. Erythematous targetoid lesions are also noted on the lower back and palms. No lesions are present on the soles or genitalia. There are small vesicles and crusts on the upper and lower lips, as well as small areas of erosion on the soft palate. His eye examination is normal. Laboratory studies reveal a normal complete blood count, comprehensive metabolic panel, and erythrocyte sedimentation rate.
Which of the following is the most likely diagnosis?
A. Acute generalized exanthematous pustulosis
B. Drug reaction with eosinophilia and systemic symptoms (DRESS)
C. “Red man syndrome”
D. Stevens-Johnson syndrome
Answers and Commentary
Correct answer: D. Stop all medications.
This patient has toxic epidermal necrolysis (TEN), which is characterized by mucous membrane involvement (eyes, oral mucosa, and genitalia in this patient), epidermal detachment affecting greater than 30% of the body surface area, and a positive Nikolsky sign (lateral pressure on nonblistered skin leads to denudation). TEN is almost always caused by a medication. The medications most closely associated with TEN are allopurinol, aromatic anticonvulsants (carbamazepine, phenytoin, phenobarbital), lamotrigine, sulfasalazine, sulfonamide antibiotics, NSAIDs, and nevirapine. In patients with TEN, survival and severity of disease are improved when the suspected causative medication and all unnecessary medications are immediately stopped.
The two most important determinants of outcome in patients with TEN are stopping all unnecessary medications and management in a burn unit.
Empiric treatment with acyclovir is not indicated because there is no evidence of an active herpes simplex infection; TEN is rarely caused by infection (including viral infections), and starting acyclovir would add an unnecessary medication.
Empiric antibiotics are not indicated in the initial management of TEN because they expose the patient to unnecessary drugs when the goal is to minimize medication exposures. However, because TEN typically results in loss of epidermis over a significant portion of the body surface area, patients are at risk for life-threatening infections during the course of the disease.
Systemic corticosteroids may be useful in the management of severe allergic drug reactions, particularly early in the course; however, clinical trials do not support the use of corticosteroids once the diagnosis of TEN is established, as their use predisposes the patient to serious side effects, including superinfection.
- The most important initial step in managing patients with toxic epidermal necrolysis is stopping the suspected causative medication, as well as stopping all unnecessary medications.
Correct answer: C. Pustular psoriasis.
An erythematous eruption that involves greater than 90% of the body surface area is indicative of erythroderma. The most common causes of erythroderma are drug eruptions, psoriasis, atopic dermatitis, and cutaneous T-cell lymphoma; however, the erythroderma may also be idiopathic. Patients such as this, who have a history of psoriasis and are treated with systemic corticosteroids, are particularly prone to developing an acute pustular erythrodermic flare days to weeks after discontinuation of the corticosteroids. The appropriate management is to treat the underlying disease (psoriasis in this patient), provide general supportive care for the erythrodermic skin, and treat complications such as temperature dysregulation, fluid and electrolyte shifts, and superinfections.
Drug hypersensitivity syndromes are classically associated with anticonvulsants, allopurinol, dapsone, and NSAIDs. They begin 3 to 6 weeks after the initiation of therapy. Angiotensin-converting enzyme inhibitors (lisinopril) are not commonly associated with hypersensitivity drug eruptions. In addition, patients with hypersensitivity drug eruptions typically present with widespread erythema that evolves over weeks rather than days and skin that is itchy more than painful, as well as facial swelling, lymphadenopathy, eosinophilia, atypical lymphocytosis, and elevated aminotransferases.
Because of this patient's history of prostate cancer, paraneoplastic erythroderma may be a consideration. However, paraneoplastic erythroderma evolves slowly over months to years rather than in a few days.
Sézary syndrome is a leukemic form of cutaneous T-cell lymphoma that evolves slowly and is intensely pruritic. A severe, fissured keratoderma and lymphadenopathy are often present. This patient's symptoms are not consistent with the diagnosis of Sézary syndrome.
Staphylococcal scalded skin syndrome (SSSS) may be difficult to differentiate from pustular psoriasis, as it also presents with widespread erythroderma and skin pain. It is most common in children less than 6 years of age, but adults with underlying immunosuppression or renal failure may be affected. This patient is an adult with normal renal function who is without significant immunosuppression. Clinical features that are characteristic of SSSS include perioral crusting and fissuring and early involvement of the intertriginous areas. The diagnosis is made clinically, but it can be confirmed by isolation of Staphylococcus aureus with bacterial culture of any suspected source of infection, blood, and mucous membranes.
- Patients with a history of psoriasis who are treated with systemic corticosteroids may develop an acute pustular erythrodermic flare days to weeks after the systemic corticosteroids are discontinued.
Correct answer: E. HIV infection.
This patient most likely has HIV infection. Herpes zoster infection is the reactivation of the varicella virus in a single cutaneous nerve. Recurrence of herpes zoster infection in the immunocompetent host is uncommon but does occur. When recurrent disease is present, the underlying cause is overwhelmingly HIV infection. In this patient, there is a band of crusts and blisters on an erythematous base along a dermatomal distribution on the left thorax. There is evidence of scarring in a dermatome several centimeters above the currently involved site, representing a previous herpes zoster infection. Almost half of all herpes zoster episodes diagnosed in patients with HIV are recurrences. The advent of highly active antiretroviral therapy has not lessened the incidence of recurrent herpes zoster infection in patients with HIV infection. Patients on chemotherapy and patients who have undergone organ transplant may also develop recurrent herpes zoster. All patients with HIV infection and herpes zoster infection are treated with antiviral therapy regardless of the age of the zoster lesions. Most patients with HIV infection can be treated with an oral antiviral drug with good bioavailability, such as valacyclovir, but patients with severe disease, evidence of dissemination, or ophthalmologic involvement may have better outcomes if treated with intravenous acyclovir.
A patient with unexplained weight loss and fatigue may have an underlying metabolic disease like diabetes mellitus, but diabetes is not associated with recurrent herpes zoster. Because of this patient's injection drug use, he is at risk for hepatitis B and hepatitis C, and screening for these infections is recommended. However, neither of these infections is associated with recurrent herpes zoster. This patient's alcoholism is a risk factor for cirrhosis but not for recurrent herpes zoster infection.
- Recurrent herpes zoster infection should trigger testing for possible associated HIV infection.
Correct answer: C. Eczema herpeticum.
The skin around the left eye has multiple coalescing, crusted vesicles on an erythematous base and is red and edematous. The presence of discrete and coalescing vesicles should immediately suggest the diagnosis of herpesvirus infection. There are also widespread, symmetrical, eczematous patches on the trunk and extremities, supporting the diagnosis of atopic dermatitis. Herpesvirus infection can locally disseminate in abnormal skin, such as that of patients with atopic dermatitis, in which the normal barrier function is lost.
Patients with eczema herpeticum may feel ill, be febrile, and have regional lymphadenopathy. The diagnosis can be confirmed by direct fluorescent antibody testing or herpes viral culture. Emergent ophthalmologic consultation should be obtained in this patient to evaluate for herpes keratitis. Primary herpes keratoconjunctivitis is treated with topical trifluorothymidine, vidarabine ointment, or acyclovir gel. Systemic antiviral therapy is typically prescribed for primary herpesvirus infection of the skin, but evidence for its efficacy is unclear. Because eczema herpeticum is considered to be a locally disseminated disease, treatment with systemic antiviral agents is appropriate. A more prolonged course may be needed for treatment of immunosuppressed patients. In some cases, hospitalization is needed for management of acutely ill patients.
Allergic contact dermatitis can cause edema and small papulovesicles in affected skin, but it does not cause the discrete vesicles that are characteristic of herpes simplex virus infection. Vesicles are not seen in atopic dermatitis. The presence of serum and crusting may suggest staphylococcal infection, and, indeed, a secondary infection is possible; however, the finding of vesicles and, later in the course of infection, punched-out–appearing ulcers or erosions is characteristic of herpes simplex virus infection.
- Patients with atopic dermatitis are more susceptible to disseminated cutaneous herpesvirus infection (eczema herpeticum).
Correct answer: D. Stevens-Johnson syndrome.
This patient has Stevens-Johnson syndrome (SJS). SJS is characterized by fever followed by the onset of erythematous macules and plaques that progress to epidermal necrosis and sloughing limited to less than 10% of the body surface area. Mucous membranes are affected in most patients, and ocular, oral, and genital surfaces may be involved. A sulfonamide is the most likely causative drug. Treatment in a burn unit is preferable for patients with extensive blistering and erosions.
Acute generalized exanthematous pustulosis (AGEP) is an exanthem that follows an infection or drug ingestion. It is characterized by the acute onset of widespread pustules that may resemble pustular psoriasis, along with fever, leukocytosis, and possibly eosinophilia. AGEP is usually self-limiting and clears without residual skin changes approximately 2 weeks after drug cessation.
Drug reaction with eosinophilia and systemic symptoms (DRESS) is characterized by a generalized papular eruption, fever, arthralgia, and generalized lymphadenopathy. Associated laboratory findings may include elevated aminotransferase levels, eosinophilia, and lymphocytosis. This patient's cutaneous and laboratory findings are not compatible with DRESS.
The “red man syndrome” (RMS) is the most common adverse reaction to vancomycin. This reaction appears not to be antibody related and is characterized by flushing, erythema, and pruritus involving primarily the upper body, neck, and face. In a few individuals, it may be associated with back and chest pain, dyspnea, and hypotension. This patient has none of the clinical findings characteristic of RMS and was not exposed to vancomycin, making RMS an unlikely diagnosis.
- Stevens-Johnson syndrome is an acute severe cutaneous reaction that is characterized by fever followed by the onset of erythematous macules and plaques that progress to epidermal necrosis and sloughing.