The
n e w e ng l a n d j o u r na l
of
m e dic i n e
Clinical Problem-Solving Caren G. Solomon, M.D., M.P.H., Editor
A Man with Fever, Cough, and Rash Bram J. Geller, M.D., Richard M. Stone, M.D., Joseph F. Merola, M.D., Bruce D. Levy, M.D., and Joseph Loscalzo, M.D., Ph.D. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors’ commentary follows. From the Departments of Medicine (B.J.G., R.M.S., J.F.M., B.D.L., J.L.) and Dermatology (J.F.M.), Brigham and Women’s Hospital and Harvard Medical School, Boston. Address reprint requests to Dr. Levy at Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115, or at blevy@partners.org.
A 67-year-old man with hairy-cell leukemia presented to the clinic with a 3-day history of fevers (with temperatures as high as 38.7°C), night sweats, arthralgias, and an erythematous, vesicular-appearing rash on his back. He had had no sick contacts, had not traveled outside the United States for more than 20 years, and had no pets at home. He reported no headaches, shortness of breath, cough, rhinorrhea, bleeding episodes, nausea, vomiting, or diarrhea.
N Engl J Med 2015;373:74-80. DOI: 10.1056/NEJMcps1404270
Infectious complications in patients with hairy-cell leukemia are common and would be my initial source of concern. Given the nature of the rash, I would also suspect disseminated viral processes, such as a herpes or varicella infection. Other viruses, such as coxsackievirus and enterovirus, may also cause a similar exanthem. Drug eruptions, early Stevens–Johnson syndrome, contact dermatitis, and autoimmune blistering diseases may also be manifested in this manner.
Copyright © 2015 Massachusetts Medical Society.
The diagnosis of hairy-cell leukemia was made 17 years before the patient’s current presentation. At that time, he had a response to chemotherapy with cladribine. The patient had a relapse 10 years before presentation, at which time the administration of cladribine was again effective, although in this instance treatment was complicated by a cardiomyopathy that subsequently resolved. Five months before his current presentation, he received eight doses of rituximab for pancytopenia due to recurrent disease, but his blood counts did not improve. The patient’s medical history was otherwise notable for prostate cancer, for which he had undergone a curative radical prostatectomy 12 years ago, and hyperlipidemia. There had been no recent change in his medications, which included 10 mg of simva statin nightly and 81 mg of aspirin daily. He also took a multivitamin. The patient was born in the United States, was retired from work in the television industry, and was married, with two children. He did not smoke, drink alcohol, or use illicit drugs. On physical examination, he appeared well and was in no acute distress. His temperature was 38.3°C, heart rate 82 beats per minute, blood pressure 136/80 mm Hg, respiratory rate 16 breaths per minute, and oxygen saturation 99% while breathing ambient air. The mucous membranes were moist. The chest examination was normal; the cardiac examination revealed a normal rate and rhythm, with no murmurs. The abdomen was soft and nontender. The skin examination revealed edematous plaques and papules, with pseudovesicular lesions that were most notable on the back (Fig. 1). His complete blood count was essentially unchanged from recent values: the white-cell count was 1600 per cubic millimeter (70% neutrophils, 28% lymphocytes,
74
n engl j med 373;1 nejm.org July 2, 2015
The New England Journal of Medicine Downloaded from nejm.org on November 16, 2017. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
Clinical Problem-Solving
and 2% eosinophils, with a calculated absolute neutrophil count of 1120 cells per cubic millimeter), the hemoglobin level was 12.9 g per deciliter, and the platelet count was 111,000 per cubic millimeter. A chest radiograph was normal. A computed tomographic (CT) scan of the chest, abdomen, and pelvis was notable for patchy ground-glass and centrilobular nodules with linear, branching (treein-bud) opacities predominantly affecting the upper lobe of the left lung (Fig. 2). There was no lymphadenopathy. The patient was admitted to the hospital and began receiving valacyclovir for a presumed viral infection and cefepime for possible pneumonia. He continued to have spiking fevers, his rash progressed to the arms and legs, and a dry, nonproductive cough developed. The evolution of the rash despite antiviral treatment and the abnormal findings on chest CT suggest nonviral infections. The CT findings are fairly nonspecific and could be consistent with bronchiolitis, early bronchopneumonia, or aspiration. In this case, tick-borne illnesses, such as Rocky Mountain spotted fever and Lyme disease, should also be considered given the arthralgias and rash, although the rash would be somewhat atypical for these diseases. Fungal infections with aspergillus, fusarium, or mucor species can also lead to infiltrated dermal plaques and fevers. In addition, mycobacterial infections, although typically more indolent, can lead to similar cutaneous findings and cough. An autoimmune cause or a drug reaction should also be considered. Cultures of blood, urine, and skin vesicles showed no organism growth. The results of urinalysis were within normal limits. A respiratory viral panel and polymerase-chain-reaction (PCR) testing for varicella–zoster virus, herpes simplex virus, and cytomegalovirus were negative, as were blood cultures and direct fluorescent antibody testing for varicella–zoster virus and herpes simplex virus. An enzyme-linked immunosorbent assay for the human immunodeficiency virus (HIV) was negative, as were tests of viral load for HIV, Epstein–Barr virus, and cytomegalovirus. PCR tests for ehrlichia and babesia were negative, as were titers for antibodies to Lyme disease and tests for coccidioides antigen, cryptococcus antigen, and histoplasmosis antigen. PCR tests were also negative for toxoplasma, adenovirus, beta-d-glucan, and galactomannan, and an interferon-gamma release assay
(IGRA) was negative for tuberculosis. The C-reactive protein level was elevated at 102.3 mg per liter (normal value,
n e w e ng l a n d j o u r na l
of
m e dic i n e
Clinical Problem-Solving Caren G. Solomon, M.D., M.P.H., Editor
A Man with Fever, Cough, and Rash Bram J. Geller, M.D., Richard M. Stone, M.D., Joseph F. Merola, M.D., Bruce D. Levy, M.D., and Joseph Loscalzo, M.D., Ph.D. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors’ commentary follows. From the Departments of Medicine (B.J.G., R.M.S., J.F.M., B.D.L., J.L.) and Dermatology (J.F.M.), Brigham and Women’s Hospital and Harvard Medical School, Boston. Address reprint requests to Dr. Levy at Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115, or at blevy@partners.org.
A 67-year-old man with hairy-cell leukemia presented to the clinic with a 3-day history of fevers (with temperatures as high as 38.7°C), night sweats, arthralgias, and an erythematous, vesicular-appearing rash on his back. He had had no sick contacts, had not traveled outside the United States for more than 20 years, and had no pets at home. He reported no headaches, shortness of breath, cough, rhinorrhea, bleeding episodes, nausea, vomiting, or diarrhea.
N Engl J Med 2015;373:74-80. DOI: 10.1056/NEJMcps1404270
Infectious complications in patients with hairy-cell leukemia are common and would be my initial source of concern. Given the nature of the rash, I would also suspect disseminated viral processes, such as a herpes or varicella infection. Other viruses, such as coxsackievirus and enterovirus, may also cause a similar exanthem. Drug eruptions, early Stevens–Johnson syndrome, contact dermatitis, and autoimmune blistering diseases may also be manifested in this manner.
Copyright © 2015 Massachusetts Medical Society.
The diagnosis of hairy-cell leukemia was made 17 years before the patient’s current presentation. At that time, he had a response to chemotherapy with cladribine. The patient had a relapse 10 years before presentation, at which time the administration of cladribine was again effective, although in this instance treatment was complicated by a cardiomyopathy that subsequently resolved. Five months before his current presentation, he received eight doses of rituximab for pancytopenia due to recurrent disease, but his blood counts did not improve. The patient’s medical history was otherwise notable for prostate cancer, for which he had undergone a curative radical prostatectomy 12 years ago, and hyperlipidemia. There had been no recent change in his medications, which included 10 mg of simva statin nightly and 81 mg of aspirin daily. He also took a multivitamin. The patient was born in the United States, was retired from work in the television industry, and was married, with two children. He did not smoke, drink alcohol, or use illicit drugs. On physical examination, he appeared well and was in no acute distress. His temperature was 38.3°C, heart rate 82 beats per minute, blood pressure 136/80 mm Hg, respiratory rate 16 breaths per minute, and oxygen saturation 99% while breathing ambient air. The mucous membranes were moist. The chest examination was normal; the cardiac examination revealed a normal rate and rhythm, with no murmurs. The abdomen was soft and nontender. The skin examination revealed edematous plaques and papules, with pseudovesicular lesions that were most notable on the back (Fig. 1). His complete blood count was essentially unchanged from recent values: the white-cell count was 1600 per cubic millimeter (70% neutrophils, 28% lymphocytes,
74
n engl j med 373;1 nejm.org July 2, 2015
The New England Journal of Medicine Downloaded from nejm.org on November 16, 2017. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
Clinical Problem-Solving
and 2% eosinophils, with a calculated absolute neutrophil count of 1120 cells per cubic millimeter), the hemoglobin level was 12.9 g per deciliter, and the platelet count was 111,000 per cubic millimeter. A chest radiograph was normal. A computed tomographic (CT) scan of the chest, abdomen, and pelvis was notable for patchy ground-glass and centrilobular nodules with linear, branching (treein-bud) opacities predominantly affecting the upper lobe of the left lung (Fig. 2). There was no lymphadenopathy. The patient was admitted to the hospital and began receiving valacyclovir for a presumed viral infection and cefepime for possible pneumonia. He continued to have spiking fevers, his rash progressed to the arms and legs, and a dry, nonproductive cough developed. The evolution of the rash despite antiviral treatment and the abnormal findings on chest CT suggest nonviral infections. The CT findings are fairly nonspecific and could be consistent with bronchiolitis, early bronchopneumonia, or aspiration. In this case, tick-borne illnesses, such as Rocky Mountain spotted fever and Lyme disease, should also be considered given the arthralgias and rash, although the rash would be somewhat atypical for these diseases. Fungal infections with aspergillus, fusarium, or mucor species can also lead to infiltrated dermal plaques and fevers. In addition, mycobacterial infections, although typically more indolent, can lead to similar cutaneous findings and cough. An autoimmune cause or a drug reaction should also be considered. Cultures of blood, urine, and skin vesicles showed no organism growth. The results of urinalysis were within normal limits. A respiratory viral panel and polymerase-chain-reaction (PCR) testing for varicella–zoster virus, herpes simplex virus, and cytomegalovirus were negative, as were blood cultures and direct fluorescent antibody testing for varicella–zoster virus and herpes simplex virus. An enzyme-linked immunosorbent assay for the human immunodeficiency virus (HIV) was negative, as were tests of viral load for HIV, Epstein–Barr virus, and cytomegalovirus. PCR tests for ehrlichia and babesia were negative, as were titers for antibodies to Lyme disease and tests for coccidioides antigen, cryptococcus antigen, and histoplasmosis antigen. PCR tests were also negative for toxoplasma, adenovirus, beta-d-glucan, and galactomannan, and an interferon-gamma release assay
(IGRA) was negative for tuberculosis. The C-reactive protein level was elevated at 102.3 mg per liter (normal value,
