The following cases and commentary, which focus on inpatient dermatology, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 16). Part A of MKSAP 16 was released on July 31.
Case 1: Leg ulcer and abdominal pain
A 27-year-old man is evaluated in the emergency department for a rapidly progressive ulcer on his leg. The ulcer is extremely tender and has been expanding over the past week. It started approximately 10 to 14 days ago. He describes the initial lesion as a “pimple.” He also notes 2 months of abdominal pain and more frequent bowel movements and watery stools, occasionally blood tinged.
On physical examination, he is afebrile and other vital signs are normal. There is no streaking erythema, fluctuance, purulent discharge, expressible pus, or sinus tracts appreciable on clinical examination. The ulcer is tender to palpation. Skin findings are shown.
Which of the following is the most likely diagnosis?
B. Ecthyma gangrenosum
C. Necrotizing fasciitis
D. Pyoderma gangrenosum
Case 2: Rash after neutropenic fever
A 37-year-old man is evaluated for a new rash. He was admitted to the hospital 2 days ago with hypotension, tachycardia, and neutropenic fever following outpatient chemotherapy for Hodgkin lymphoma. He was doing well, with excellent performance status, until hospital admission. His initial physical examination and imaging studies did not reveal the source of the fever. He was started on ceftazidime.
On physical examination, temperature is 37.9°C (100.2°F), blood pressure is 138/78 mm Hg, pulse rate is 87/min, and respiration rate is 12/min. BMI is 28. He appears improved. The general physical examination is normal. Today's absolute neutrophil count is 490/µL (0.490 × 109/L). Blood and urine cultures are negative. Skin findings are shown.
Which of the following intervention is most appropriate?
A. Cooling measures
B. Discontinue ceftazidime
C. Hypoallergenic sheets
D. Oral corticosteroids
Case 3: Elderly woman with blistering skin
A 75-year-old woman is evaluated in the emergency department for skin blistering. Her symptoms began 4 days ago when she developed fatigue, malaise, and headache. Her eyes felt dry and gritty 2 nights ago. When she awoke yesterday, her skin was pink-red and blistered with some broken blisters oozing fluid and leaving patches of raw skin. The lesions have rapidly progressed over the past 24 hours. Ten days ago, she received trimethoprim-sulfamethoxazole for a urinary tract infection.
On physical examination, temperature is 39.1°C (102.4°F), blood pressure is 100/75 mm Hg, pulse rate is 115/min, and respiration rate is 20/min. There is generalized erythema of the entire body, with blistering and erosions affecting greater than 30% of the body surface area. Lateral pressure on erythematous, nonblistered skin causes the skin to slough. There is conjunctival hyperemia, the lips are crusted, and there are ulcers inside the mouth. Skin findings are shown.
The leukocyte count is 12,500/µL (12.5 × 109/L) with 15% eosinophils. The serum alanine aminotransferase and aspartate aminotransferase levels are elevated.
Which of the following is the most likely diagnosis?
A. Erythema multiforme major
B. Pemphigus foliaceus
C. Staphylococcal scalded skin syndrome
D. Toxic epidermal necrolysis
Case 4: Chronic painful leg lesions
A 74-year-old woman is admitted to the hospital for chronic, painful leg lesions that recently ulcerated. She has had painful subcutaneous nodules for 4 weeks' duration. Medical history is significant for end-stage kidney disease requiring hemodialysis. This morning during dialysis, it was noted that one of the lesions had turned dark and appeared to ulcerate spontaneously. The patient is in constant pain from her legs, which is generally a persistent dull pain in the skin. She has no fever. She has no known drug allergies. Medications are epoetin alfa, lisinopril, metoprolol, nifedipine, sevelamer, and daily aspirin.
On physical examination, temperature is 37.3°C (99.2°F), blood pressure is 132/72 mm Hg, pulse rate is 88/min, and BMI is 31. There are reticulated purpuric patches on the bilateral thighs; these are tender to palpation, and there is an appreciable subcutaneous nodular component. Skin findings are shown.
Laboratory studies show calcium 10.1 mg/dL (2.5 mmol/L), parathyroid hormone 726 pg/mL (726 ng/L) and phosphorus 7.2 mg/dL (2.3 mmol/L),
Which of the following is the most likely diagnosis?
B. Nephrogenic systemic fibrosis
C. Polyarteritis nodosa
D. Pyoderma gangrenosum
Case 5: Migrating wheals
A 43-year-old woman is evaluated in the emergency department for widespread pruritic wheals. The individual lesions seem to migrate, with each wheal lasting 30 to 60 minutes. The patient says this has been going on for 2 days. There is no accompanying wheezing and no lip or eyelid swelling. The patient is breathing comfortably, has no difficulty swallowing or clearing secretions, and no skin pain. She took diphenhydramine twice yesterday without relief. She has no known drug allergies and just finished a 3-day course of levofloxacin for her third urinary tract infection in the past 6 months.
On physical examination, temperature is normal, blood pressure is 110/78 mm Hg, pulse rate is 90/min, respiration rate is 18/min. BMI is 22. There are scattered edematous indurated erythematous plaques consistent with wheals over the scalp, face, neck, chest, upper back, flanks, and arms. The patient has marked dermatographism. There is no wheezing or stridor, no mucosal lesions, and no bullae.
Which of the following is the most appropriate management?
A. Admit patient to the hospital
B. Treat with cetirizine, ranitidine, and diphenhydramine
C. Treat with topical high-dose prednisone
D. Treat with indomethacin
Answers and commentary
Correct answer: D. Pyoderma gangrenosum.
The appearance of the ulcer is suggestive of pyoderma gangrenosum (PG). PG is an uncommon, neutrophilic, ulcerative skin disease. Lesions tend to be multiple and tend to appear on the lower extremities. They begin as tender papules, pustules, or vesicles that spontaneously ulcerate and progress to painful ulcers with a purulent base and undermined, ragged, violaceous borders. Lesions often exhibit a sharp, “cliff-face” cut-off between normal skin and the ulcer itself. Inflammatory bowel disease is the most common underlying association reported in conjunction with PG. Other conditions associated with PG include rheumatoid arthritis, seronegative spondyloarthritis, and a hematologic disease or malignancy, most commonly acute myeloid leukemia.
Calciphylaxis is a painful ulcerative process due to ectopic calcification of the arteries feeding the skin. Calciphylaxis nearly always occurs in patients with end-stage kidney disease in the setting of very high calcium-phosphorus products and manifests with reticulated dusky erythema that then ulcerates due to cutaneous ischemia.
Ecthyma gangrenosum results from perivascular bacterial invasion of blood vessel walls with secondary ischemic necrosis. Multiple lesions may be present at different stages of development. The infecting agent is usually Pseudomonas aeruginosa and almost always occurs in a significantly immunocompromised patient who is clinically ill.
Necrotizing fasciitis is a rapidly progressive infection of the subcutis, often from a streptococcal infection or polymicrobial flora. Patients are critically ill, and the disease progresses over hours, not days or weeks. Patients typically have extreme pain, dull or dusky skin, potentially with crepitus, and a clinical picture of sepsis.
- Pyoderma gangrenosum is an uncommon, neutrophilic, ulcerative skin disease associated with inflammatory bowel disease, rheumatoid arthritis, seronegative spondyloarthritis, or a hematologic disease or malignancy, most commonly acute myeloid leukemia.
Correct answer: A. Cooling measures.
This patient most likely has miliaria, and the most appropriate therapy begins with cooling the patient with air-conditioning, a fan, or a cool bath. Talcum or cornstarch powder may be used to dry the skin. Because miliaria or “heat rash” is caused by blockage and rupture of the eccrine sweat ducts, it occurs when the skin is hot and occluded, such as in immobile, hospitalized, febrile patients. The diagnosis of miliaria is based entirely on clinical findings and should be suspected in hospitalized patients with a rash confined to the dependent parts of the body. There are several forms of miliaria (crystallina, rubra, pustulosa, and profunda) that are differentiated by the presence of vesicles, papules, and pustules and the degree of associated inflammation. Symptoms of miliaria are itching, burning, and prickling. Miliaria may be mistaken for a cutaneous drug reaction; however, a drug reaction would be more generalized to the anterior as well as posterior surfaces. Cutaneous drug reactions can be papular but often also have macules, large patches, and plaques.
The ceftazidime should be continued until his absolute neutrophil count is greater than 500/µL (0.500 × 109/L) and he becomes afebrile. It would be premature to discontinue the antibiotic at this time.
The use of hypoallergenic sheets is not an appropriate therapy because miliaria is not a manifestation of a cutaneous or systemic allergy.
Oral corticosteroids are not used to manage miliaria because they may predispose the patient to additional metabolic and infectious complications. Occasionally low-potency topical corticosteroids can be used when patients have significant pruritus.
- Miliaria presents as small erythematous papules or papulovesicles associated with itching, burning, and prickling and is best treated with cooling measures.
Correct answer: D. Toxic epidermal necrolysis.
This patient has toxic epidermal necrolysis (TEN), which is a potentially lethal condition. TEN typically begins with a prodrome of fever, sore throat, or a burning sensation in the eyes 1 to 3 days before skin lesions appear. Skin findings may be characterized by flat, atypical, purpuric, targetoid lesions that coalesce into dusky, poorly demarcated, confluent patches (TEN “with spots”) or may consist of confluent, tender erythema without identifiable individual lesions (TEN “without spots”). The involved epidermis blisters and sloughs, leaving behind denuded dermis. Skin pain is prominent. Two or more mucosal surfaces, such as the eyes, nasopharynx, mouth, and genitals, are involved in more than 80% of cases. Other findings include 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 most commonly caused by medications; antiepileptic agents, NSAIDs, antibiotics, pantoprazole, sertraline, tramadol, and allopurinol are the most frequently implicated drugs. HIV infection, kidney disease, active autoimmune disease, and human leukocyte antigen type also contribute to increased risk. The reaction occurs within 8 weeks of drug initiation, most commonly between 4 and 28 days. Vesicles, bullae, and erosions reflect the extensive epidermal necrosis seen on biopsy. Diagnosis is often made clinically, but a biopsy can be supportive, although it cannot distinguish among erythema multiforme, Stevens-Johnson syndrome, and TEN. In patients with TEN, survival and severity of disease are improved when the suspected causative medication and all unnecessary medications are immediately stopped.
Erythema multiforme (EM) is an acute, often recurrent mucocutaneous eruption that usually follows an acute infection, most frequently recurrent herpes simplex virus infection, but it may also be drug related or idiopathic. Lesions range in size from several millimeters to several centimeters and consist of erythematous plaques with concentric rings of color. Patients may have low-grade fever during an EM outbreak. This patient's skin lesions are not consistent with EM, and EM does not cause lymphadenopathy, serum aminotransferase elevations, or eosinophilia. Pemphigus foliaceus is an autoimmune blistering disease that can result in scaling and crusted lesions on face and upper trunk, erythroderma, and a positive Nikolsky sign. Pemphigus foliaceous does not involve the mucosa and does not produce the extensive epidermal detachment that is associated with TEN.
Staphylococcal scalded skin syndrome (SSSS) is most common in children, but adults with underlying immunosuppression or acute kidney injury may be affected. Clinical features that are characteristic of SSSS include perioral crusting and fissuring and early involvement of the intertriginous areas. Skin detachment and mucosal involvement do not occur.
- Toxic epidermal necrolysis is a potentially lethal drug eruption with acute onset of widespread skin and mucosal necrosis.
Correct answer: A. Calciphylaxis.
This patient most likely has calciphylaxis, also known as uremic calcific arteriopathy. Calciphylaxis is a rare condition that almost always occurs in patients with end-stage kidney disease who are on renal replacement therapy and who have abnormally elevated serum calcium-phosphorus products (frequently >55-70 mg2/dL2). Patients will frequently have markedly elevated serum parathyroid hormone levels as well. Calciphylaxis usually presents with angulated purpuric nonblanching patches with associated subcutaneous nodules as a result of the metastatic soft-tissue calcification and vascular calcification leading to abnormal blood flow to the skin and subcutis. The skin often becomes ischemic and is usually very painful. Calciphylaxis has a poor prognosis, and patients frequently develop bacterial colonization and secondary bacteremia and sepsis.
Nephrogenic systemic fibrosis is characterized by yellowish, thickened papules and nodules with progressive skin tightening and sclerosis, usually proceeding from the distal extremities proximally, in patients with end-stage kidney disease who have been exposed to gadolinium in MRI contrast dyes. Nephrogenic systemic fibrosis does not usually cause vascular changes as described here.
Polyarteritis nodosa may present with retiform purpura and subcutaneous nodules, and in some patients may ulcerate. Polyarteritis nodosa is not associated with end-stage kidney disease. Additionally, the markedly elevated parathyroid hormone level and calcium-phosphorus product make calciphylaxis a much more likely diagnosis.
Pyoderma gangrenosum normally presents as an ulceration without associated subcutaneous nodules. Although pyoderma gangrenosum may have an inflammatory border, sometimes described as a violaceous overhanging edge, it should not result in angulated purpuric patches. Angulations, or retiform patterns, suggest a vascular process. Pyoderma gangrenosum is not usually associated with chronic kidney disease or complications of kidney disease.
- Calciphylaxis lesions are intensely painful, angulated, retiform purpuric patches with areas of black necrotic tissue that may form bullae, ulcerate, and leave a hard, firm eschar.
Correct answer: B. Treat with cetirizine, ranitidine, and diphenhydramine.
This patient is presenting with acute urticaria, most likely as a result of her levofloxacin exposure and should be treated with cetirizine, ranitidine, and diphenhydramine. Although she has widespread cutaneous involvement with multiple hives, the patient lacks concerning features such as wheezing, stridor, or lip, tongue, or eyelid swelling, and she is breathing comfortably and able to clear secretions. First-line treatment for acute urticaria is antihistamine therapy. Combination H1- and H2-histamine blockers may be more effective than single-agent therapy alone.
Whereas this patient has widespread cutaneous wheals consistent with acute urticaria, she does not have any features suggesting angioedema or impending airway collapse. If she did exhibit dyspnea, difficulty clearing her secretions, or had lip or tongue swelling, admission to the hospital for monitoring may be warranted.
Topical corticosteroids can occasionally provide additional relief for symptomatic urticarial lesions, but given this patient's widespread urticarial eruption, it would be impractical and inappropriate to treat with topical therapy alone.
Indomethacin is an NSAID and can cause mast-cell degranulation and worsen urticaria. It has no role in the management of this condition.
- Combination H1- and H2-antihistamines are the first-line therapy for patients with acute urticaria.