Clinical Review & Education
JAMA Oncology Clinical Challenge
Lesion on the Plantar Foot Timothy H. Almazan, MD; Jasmine Zain, MD; Jae Y. Jung, MD, PhD
A Grouped, brown, flat-topped papules on the plantar foot
B
Erythematous plaques on the posterior left thigh
Figure. Photographs of a patient with painful lesions on the foot.
A 50-year-old man with transformed marginal zone lymphoma presented with intensely painful lesions on his left foot for 2 days. He noted a childhood history of plantar warts and believed these lesions to be identical in appearance. He did not recall any injury or unusual exposure. He had received his third cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) 2 weeks prior to presentation as well as an injection of granulocyte-colony stimulating factor. He was anticipatQuiz at jamaoncology.com ing his fourth cycle of treatment the day of his presentation. He also complained of a pruritic rash on his left thigh that had started several days before the appearance of his plantar foot lesions. The patient was afebrile, and his vital signs were within normal limits. Physical examination revealed grouped, brown, flat-topped papules on his distal plantar left foot (Figure). It was exquisitely tender to palpation, and the patient was visibly uncomfortable when walking. He also demonstrated erythematous papules and plaques on his posterolateral thigh. A few areas had shallow erosions. Laboratory studies revealed pancytopenia, with a white blood cell count of 2800/μL, hemoglobin level of 11.6 g/dL, and a platelet count of 81 × 103/μL. His lactate dehydrogenase level was elevated at 914 U/L, and results of his comprehensive metabolic panel were unremarkable. (To convert white blood cell count to ×109/L, multiply by 0.001; to convert hemoglobin to grams per liter, multiply by 10; to convert lactate dehydrogenase to microkatals per liter, multiply by 0.0167.)
jamaoncology.com
WHAT IS YOUR DIAGNOSIS?
A. Plantar warts B. Shingles C. Cutaneous lymphoma D. Toxic erythema of chemotherapy
(Reprinted) JAMA Oncology September 2015 Volume 1, Number 6
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://oncology.jamanetwork.com/ by a UQ Library User on 10/04/2015
833
Clinical Review & Education JAMA Oncology Clinical Challenge
Diagnosis B. Shingles
Discussion Direct fluorescence antigen testing and polymerase chain reaction (PCR) were performed on skin scrapings and confirmed the diagnosis of herpes zoster (shingles) in an unusual S2 dermatomal distribution. While the brown, flat-topped papules on the plantar aspect of the foot resemble warts, they lacked the characteristic dot-like structures and verrucous appearance. The patient’s scheduled chemotherapy for that day was cancelled, and he was started on valacyclovir, 1 g 3 times daily. Rapid clinical diagnosis is critical when patients are receiving chemotherapy, especially with cytopenia, to minimize the risk of disseminated infection. Chemotherapy was resumed 2 weeks later when he had recovered from the herpes zoster and all lesions had crusted over. A history of primary varicella zoster infection is nearly universal in adult populations of North America and results in the diffuse vesicular rash of varicella (chicken pox).1 Following primary infection, the varicella zoster virus (VZV) establishes latency within sensory dorsal root ganglia; reactivation manifests as herpes zoster and is typically heralded by a painful, unilateral vesicular eruption in a dermatomal distribution. According to Centers for Disease Control and Prevention estimates, 32% of Americans will experience herpes zoster during their lifetimes.2 The incidence of herpes zoster is higher in immunocompromised patients, particularly those with lymphoproliferative malignant neoplasms.3 In 13% to 50% of patients with lymphoma, herpes zoster may present with life-threatening, disseminated disease involving multiple, nonadjacent dermatomes as well as visceral sites.3 Disseminated disease is associated with a 6% to 17% mortality rate.4 In patients with cancer, an elevated risk of localized or disseminated VZV infection exists in patients specifically with Hodgkin disease, lymphoproliferative malignant lesions, lung cancer, and among those who received bone marrow transplantation.4 ARTICLE INFORMATION Author Affiliations: Division of Dermatology, City of Hope Comprehensive Cancer Center, Duarte, California (Almazan, Jung); Department of Hematology and Hematopoietic Cell Transplantation, T-Cell Lymphoma Program, City of Hope Comprehensive Cancer Center, Duarte, California (Zain). Corresponding Author: Jae Y. Jung, MD, PhD, Division of Dermatology, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 ([email protected]). Published Online: July 9, 2015. doi:10.1001/jamaoncol.2015.2107. Conflict of Interest Disclosures: None reported. REFERENCES 1. Habel LA, Ray GT, Silverberg MJ, et al. The epidemiology of herpes zoster in patients with newly diagnosed cancer. Cancer Epidemiol Biomarkers Prev. 2013;22(1):82-90.
834
Theincidenceofherpeszosterinfectionissignificantlyhigherinpatientswithlymphomacomparedwiththosewithnonhematologicsolid tumors, and risk factors include advanced stage and recent radiation therapy.5 A retrospective cohort study of adult patients with cancer noted the incidence of herpes zoster to be 31 per 1000 person-years for patients with hematologic malignant neoplasms and 12 per 1000 person-yearsinthosewithsolidtumors.Patientswithhematologicmalignantneoplasmsweretwiceaslikelytodevelopherpeszosterasthose with solid tumors and 5 times more likely than the general population.1 Zostavax is a live, attenuated zoster vaccine, and administration may result in disseminated disease in the immunosuppressed. It is therefore contraindicated in patients with primary or acquired immunodeficiencystates,includingleukemia,lymphoma,orothermalignant neoplasms affecting the bone marrow or lymphatic system.6 The Advisory Committee on Immunization Practices states that patients with leukemia in remission may receive the zoster vaccine as long as no chemotherapy or radiation was given in the past 3 months.6 Tseng et al7 suggested that the zoster vaccine affords effective protection when given to adults 60 years or older who subsequently were diagnosed as having cancer and had received chemotherapy. In summary, herpes zoster in the lumbar and sacral dermatomes can present with lesions in seemingly unrelated distribution (lateral thigh and plantar foot) and has multiple clinical presentations (wartlike and rashlike). Clinicians should maintain a high index of suspicion for herpes zoster in patients with cancer, especially those receiving chemotherapy. The quality of the pain out of proportion to the examination is often an indicator of herpes zoster infection. Treatment should be started empirically. Direct fluorescent antigen (DFA) testing on scrapings from active vesicular lesions is a rapid method for the detection of the virus and has a sensitivity and specificity of 88% and 94%, respectively. A VZVspecific PCR is often used in the instance where the results from DFA testing is negative but clinical suspicion for herpes zoster remains high. Sensitivity and specificity are both higher for PCR testing (97.6 and 100%, respectively).8
2. Harpaz R, Ortega-Sanchez IR, Seward JF; Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;57(RR-5):1-30. 3. Mazur MH, Dolin R. Herpes zoster at the NIH: a 20 year experience. Am J Med. 1978;65(5):738-744. 4. Rusthoven JJ, Ahlgren P, Elhakim T, Pinfold P, Stewart L, Feld R. Risk factors for varicella zoster disseminated infection among adult cancer patients with localized zoster. Cancer. 1988;62(8):1641-1646.
7. Tseng HF, Tartof S, Harpaz R, et al. Vaccination against zoster remains effective in older adults who later undergo chemotherapy. Clin Infect Dis. 2014; 59(7):913-919. 8. Wilson DA, Yen-Lieberman B, Schindler S, Asamoto K, Schold JD, Procop GW. Should varicella-zoster virus culture be eliminated? a comparison of direct immunofluorescence antigen detection, culture, and PCR, with a historical review. J Clin Microbiol. 2012;50(12): 4120-4122.
5. Schimpff S, Serpick A, Stoler B, et al. Varicella-zoster infection in patients with cancer. Ann Intern Med. 1972;76(2):241-254. 6. National Center for Immunization and Respiratory Diseases. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60(2):1-64.
JAMA Oncology September 2015 Volume 1, Number 6 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://oncology.jamanetwork.com/ by a UQ Library User on 10/04/2015
jamaoncology.com
JAMA Oncology Clinical Challenge
Lesion on the Plantar Foot Timothy H. Almazan, MD; Jasmine Zain, MD; Jae Y. Jung, MD, PhD
A Grouped, brown, flat-topped papules on the plantar foot
B
Erythematous plaques on the posterior left thigh
Figure. Photographs of a patient with painful lesions on the foot.
A 50-year-old man with transformed marginal zone lymphoma presented with intensely painful lesions on his left foot for 2 days. He noted a childhood history of plantar warts and believed these lesions to be identical in appearance. He did not recall any injury or unusual exposure. He had received his third cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) 2 weeks prior to presentation as well as an injection of granulocyte-colony stimulating factor. He was anticipatQuiz at jamaoncology.com ing his fourth cycle of treatment the day of his presentation. He also complained of a pruritic rash on his left thigh that had started several days before the appearance of his plantar foot lesions. The patient was afebrile, and his vital signs were within normal limits. Physical examination revealed grouped, brown, flat-topped papules on his distal plantar left foot (Figure). It was exquisitely tender to palpation, and the patient was visibly uncomfortable when walking. He also demonstrated erythematous papules and plaques on his posterolateral thigh. A few areas had shallow erosions. Laboratory studies revealed pancytopenia, with a white blood cell count of 2800/μL, hemoglobin level of 11.6 g/dL, and a platelet count of 81 × 103/μL. His lactate dehydrogenase level was elevated at 914 U/L, and results of his comprehensive metabolic panel were unremarkable. (To convert white blood cell count to ×109/L, multiply by 0.001; to convert hemoglobin to grams per liter, multiply by 10; to convert lactate dehydrogenase to microkatals per liter, multiply by 0.0167.)
jamaoncology.com
WHAT IS YOUR DIAGNOSIS?
A. Plantar warts B. Shingles C. Cutaneous lymphoma D. Toxic erythema of chemotherapy
(Reprinted) JAMA Oncology September 2015 Volume 1, Number 6
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://oncology.jamanetwork.com/ by a UQ Library User on 10/04/2015
833
Clinical Review & Education JAMA Oncology Clinical Challenge
Diagnosis B. Shingles
Discussion Direct fluorescence antigen testing and polymerase chain reaction (PCR) were performed on skin scrapings and confirmed the diagnosis of herpes zoster (shingles) in an unusual S2 dermatomal distribution. While the brown, flat-topped papules on the plantar aspect of the foot resemble warts, they lacked the characteristic dot-like structures and verrucous appearance. The patient’s scheduled chemotherapy for that day was cancelled, and he was started on valacyclovir, 1 g 3 times daily. Rapid clinical diagnosis is critical when patients are receiving chemotherapy, especially with cytopenia, to minimize the risk of disseminated infection. Chemotherapy was resumed 2 weeks later when he had recovered from the herpes zoster and all lesions had crusted over. A history of primary varicella zoster infection is nearly universal in adult populations of North America and results in the diffuse vesicular rash of varicella (chicken pox).1 Following primary infection, the varicella zoster virus (VZV) establishes latency within sensory dorsal root ganglia; reactivation manifests as herpes zoster and is typically heralded by a painful, unilateral vesicular eruption in a dermatomal distribution. According to Centers for Disease Control and Prevention estimates, 32% of Americans will experience herpes zoster during their lifetimes.2 The incidence of herpes zoster is higher in immunocompromised patients, particularly those with lymphoproliferative malignant neoplasms.3 In 13% to 50% of patients with lymphoma, herpes zoster may present with life-threatening, disseminated disease involving multiple, nonadjacent dermatomes as well as visceral sites.3 Disseminated disease is associated with a 6% to 17% mortality rate.4 In patients with cancer, an elevated risk of localized or disseminated VZV infection exists in patients specifically with Hodgkin disease, lymphoproliferative malignant lesions, lung cancer, and among those who received bone marrow transplantation.4 ARTICLE INFORMATION Author Affiliations: Division of Dermatology, City of Hope Comprehensive Cancer Center, Duarte, California (Almazan, Jung); Department of Hematology and Hematopoietic Cell Transplantation, T-Cell Lymphoma Program, City of Hope Comprehensive Cancer Center, Duarte, California (Zain). Corresponding Author: Jae Y. Jung, MD, PhD, Division of Dermatology, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 ([email protected]). Published Online: July 9, 2015. doi:10.1001/jamaoncol.2015.2107. Conflict of Interest Disclosures: None reported. REFERENCES 1. Habel LA, Ray GT, Silverberg MJ, et al. The epidemiology of herpes zoster in patients with newly diagnosed cancer. Cancer Epidemiol Biomarkers Prev. 2013;22(1):82-90.
834
Theincidenceofherpeszosterinfectionissignificantlyhigherinpatientswithlymphomacomparedwiththosewithnonhematologicsolid tumors, and risk factors include advanced stage and recent radiation therapy.5 A retrospective cohort study of adult patients with cancer noted the incidence of herpes zoster to be 31 per 1000 person-years for patients with hematologic malignant neoplasms and 12 per 1000 person-yearsinthosewithsolidtumors.Patientswithhematologicmalignantneoplasmsweretwiceaslikelytodevelopherpeszosterasthose with solid tumors and 5 times more likely than the general population.1 Zostavax is a live, attenuated zoster vaccine, and administration may result in disseminated disease in the immunosuppressed. It is therefore contraindicated in patients with primary or acquired immunodeficiencystates,includingleukemia,lymphoma,orothermalignant neoplasms affecting the bone marrow or lymphatic system.6 The Advisory Committee on Immunization Practices states that patients with leukemia in remission may receive the zoster vaccine as long as no chemotherapy or radiation was given in the past 3 months.6 Tseng et al7 suggested that the zoster vaccine affords effective protection when given to adults 60 years or older who subsequently were diagnosed as having cancer and had received chemotherapy. In summary, herpes zoster in the lumbar and sacral dermatomes can present with lesions in seemingly unrelated distribution (lateral thigh and plantar foot) and has multiple clinical presentations (wartlike and rashlike). Clinicians should maintain a high index of suspicion for herpes zoster in patients with cancer, especially those receiving chemotherapy. The quality of the pain out of proportion to the examination is often an indicator of herpes zoster infection. Treatment should be started empirically. Direct fluorescent antigen (DFA) testing on scrapings from active vesicular lesions is a rapid method for the detection of the virus and has a sensitivity and specificity of 88% and 94%, respectively. A VZVspecific PCR is often used in the instance where the results from DFA testing is negative but clinical suspicion for herpes zoster remains high. Sensitivity and specificity are both higher for PCR testing (97.6 and 100%, respectively).8
2. Harpaz R, Ortega-Sanchez IR, Seward JF; Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;57(RR-5):1-30. 3. Mazur MH, Dolin R. Herpes zoster at the NIH: a 20 year experience. Am J Med. 1978;65(5):738-744. 4. Rusthoven JJ, Ahlgren P, Elhakim T, Pinfold P, Stewart L, Feld R. Risk factors for varicella zoster disseminated infection among adult cancer patients with localized zoster. Cancer. 1988;62(8):1641-1646.
7. Tseng HF, Tartof S, Harpaz R, et al. Vaccination against zoster remains effective in older adults who later undergo chemotherapy. Clin Infect Dis. 2014; 59(7):913-919. 8. Wilson DA, Yen-Lieberman B, Schindler S, Asamoto K, Schold JD, Procop GW. Should varicella-zoster virus culture be eliminated? a comparison of direct immunofluorescence antigen detection, culture, and PCR, with a historical review. J Clin Microbiol. 2012;50(12): 4120-4122.
5. Schimpff S, Serpick A, Stoler B, et al. Varicella-zoster infection in patients with cancer. Ann Intern Med. 1972;76(2):241-254. 6. National Center for Immunization and Respiratory Diseases. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60(2):1-64.
JAMA Oncology September 2015 Volume 1, Number 6 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://oncology.jamanetwork.com/ by a UQ Library User on 10/04/2015
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