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VOLUME 71, NUMBER 3
Medicine,d Medical University of South Carolina, Charleston Funding sources: None. Conflicts of interest: None declared.
Fig 1. Primary aggressive CD81 cytotoxic T-cell (Berti) lymphoma following adalimumab. Extremity with papulosquamous plaques clinically suggestive of psoriasis.
Fig 2. Biopsy of an ulcer on the chest exhibited an epidermotropic CD81 infiltrate of atypical T-cells. (Hematoxylin-eosin stain; original magnification 310.)
lymphomas after TNF-alpha blockade has been reported.4,5 TNF-alpha blockade likely inhibits both innate and acquired immunity and may compromise immune surveillance for malignancy.5 The relation between our patient’s dermatitis and her Berti lymphoma is unclear. Her dermatitis may have represented a smoldering CTCL that transformed into Berti lymphoma, or the latter may have developed anew in the setting of immunosuppression. This case suggests that corticosteroid-refractory, histologically nonspecific dermatitis should be evaluated carefully and managed cautiously. Not all psoriasiform dermatitis is psoriasis or is safely treated as such. A high suspicion for possible CTCL and a low threshold for repeat biopsies to establish a diagnosis should be maintained when considering immunomodulatory therapy. Sarah M. Jacks, BA,a Brent R. Taylor, MD,b Raford P. Rogers III, MD,c Jonathan S. Ralston, MD,d John S. Metcalf, MD,d and John Lazarchick, MDd School of Medicinea and Department of Dermatology and Dermatologic Surgery,b Medical University of South Carolina, Charleston; Athens Regional Pathology Associates,c Georgia; Department of Pathology and Laboratory
Correspondence to: Brent R. Taylor, MD, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, 135th Rutledge Avenue, Charleston, South Carolina 29425 E-mail: [email protected] REFERENCES 1. Willemze R, Meijer CJ. Classification of cutaneous T-cell lymphoma: From Alibert to WHO-EORTC. J Cutan Pathol 2006;33(1 Suppl):18-26. 2. Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al. WHO-EORTC classification for cutaneous lymphomas. Blood 2005;105:3768. 3. Berti E, Tomasini D, Vermeer MH, Meijer CJ, Alessi E, Willemze R. Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas: a distinct clinicopathological entity with an aggressive clinical behavior. Am J Pathol 1999;155:483-92. 4. Dalle S, Balme B, Berger F, Hayett S, Thomas L. Mycosis fungoides-associated follicular mucinosis under adalimumab. Br J Dermatol 2005;153:207-8. 5. Adams AE, Zwicker J, Curiel C, Kadin ME, Falchuk KR, Drews R, et al. Aggressive cutaneous T-cell lymphomas after TNFalpha blockade. J Am Acad Dermatol 2004;51:660-2. http://dx.doi.org/10.1016/j.jaad.2014.03.022
Rickettsia parkeri: Eschar diagnosis To the Editor: A 30-year-old Caucasian woman presented to the emergency department in June with a 5-day history of flu-like symptoms. She denied recent travel from her residence, Columbiana, Alabama. She was in her usual state of health until she experienced a tick bite on her forearm 7 days before admission. Following tick removal, she noticed fatigue, myalgias, arthralgias, and severe headache, with retro-orbital pain. A temperature up to 1058F recalcitrant to antipyretics accompanied her symptoms. On examination, the patient was febrile with a temperature of 105.78F. Although she was hemodynamically stable, notable laboratory results included thrombocytopenia ( platelets: 133,000 109/L). No maculopapular rash was noted. An ulcerated nodule with a central eschar was noted on her right forearm (Fig 1). The eschar was biopsied by punch technique with half of the specimen processed routinely, while the other half was snap frozen in liquid nitrogen and sent to the Centers for Disease Control and Prevention (CDC) for further study.
e88 Letters
Fig 1. Rickettsia parkeri infection. Clinical image of cutaneous lesion on right forearm. Ulcerated nodule with central eschar.
Fig 2. Rickettsia parkeri infection. Histopathology of cutaneous punch biopsy of eschar. A nodular and diffuse lymphoid infiltrate permeates the superficial and deep dermis and extends focally into the subcutaneous fat. There is overlying ulcer and crust with associated necrosis extending to the mid dermis. (Hematoxylin-eosin stain; original magnification: 320.) Inset: Small to medium sized vessel with lymphocytic vasculitis showing endothelial swelling and fibrin thrombi (arrowhead ) and perineural inflammation (arrow). (Hematoxylin-eosin stain; original magnification: 3200.)
Histopathologic section study demonstrated a marked lymphocytic vasculitis with associated ulcer and dermal necrosis (Fig 2). Polymerase chain reaction (PCR)-based testing performed at the CDC was positive for spotted fever group rickettsiae. Gene sequencing confirmed presence of Rickettsia parkeri. The patient’s blood cultures were negative, as was serologic study for Borrelia burgdorferi and
J AM ACAD DERMATOL
SEPTEMBER 2014
Ehrlichia chaffeensis antibodies. No serologic tests for rickettsial organisms were obtained by primary team. Treatment in the emergency department included fluids and doxycycline. She was afebrile after 3 days on doxycycline and was discharged home with a 17-day course of doxycycline. She recovered without sequelae. Rickettsia parkeri is a spotted fever group rickettsia first documented in 2004 to cause human infection.1-3 Rickettsia parkeri infections in the United States and South America are a clinical rarity, with 27 cases having been reported in the English literature.1,4 Other spotted fever group rickettsiae include Rickettsia felis, Rickettsia 364D, and Rickettsia massiliae. Documented cases reveal a disease that is milder than classically described Rocky Mountain spotted fever: typical symptoms include local lymphadenopathy, fever, headache, myalgias, inoculation eschar, and a maculopapular exanthem.5 While patients with Rocky Mountain spotted fever rarely present with eschars, R. parkeri has been confused with Rickettsia akari, a mite-borne causative agent of eschar-associated rickettsialpox. Even though most American cases of rickettsialpox have occurred in inner city areas of northeastern states, recent cases have been reported in areas endemic to R. parkeri, such as rural North Carolina.5 Once the broad differential diagnosis of the febrile patient presenting with eschar has been narrowed down to the spotted fever group, diagnostic difficulty remains in obtaining a speciesspecific diagnosis. In traditional serologic assays, antibodies generated to R. parkeri antigens can cross-react with those of R. rickettsia and R. akari.5 While serology can define a diagnosis in select cases, an accurate species-specific diagnosis can be made by sending fresh skin biopsy specimens of the eschar and rash lesions to an appropriate reference laboratory for PCR or culture-based assays.1,5 Based on the literature, we suggest quantitative real-time PCR targeting the R. parkeri species-specific Rpark using DNA extracted from eschar specimens to be the gold standard for diagnosis.1,2 We are indebted to the University of Alabama at Birmingham Department of Medicine, Division of Infectious Diseases, and Department of Dermatology for their administrative support.
Nadine M. Kaskas, BS,a Johnathan J. Ledet, MD,b Alexander Wong, MD,b Christina A. Muzny, MD,c Latesha Elopre, MD,c and Lauren Hughey, MDb Louisiana State University Health School of Medicine, Shreveporta; Department of Dermatologyb
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and Department of Medicine, Division of Infectious Diseases,c University of Alabama, Birmingham Funding sources: None. Conflicts of interest: None declared. Correspondence to: Nadine M. Kaskas, BS, Box 253, Louisiana State University Health School of Medicine, Shreveport, LA 71103 E-mail: [email protected] REFERENCES 1. Myers T, Lalani T, Dent M, Jiang J, Daly PL, Maguire JD, et al. Detecting Rickettsia parkeri infection from eschar swab specimens. Emerg Infect Dis 2013;19:778-80. 2. Paddock CD, Fournier PE, Sumner JW, Goddard J, Elshenawy Y, Metcalfe MG, et al. Isolation of Rickettsia parkeri and identification of a novel spotted fever group Rickettsia sp from Gulf Coast ticks (Amblyomma maculatum) in the United States. Appl Environ Microbiol 2010;76:2689-96. 3. Paddock CD, Sumner JW, Comer JA, Zaki SR, Goldsmith CS, Goddard J, et al. Rickettsia parkeri: a newly recognized cause of spotted fever rickettsiosis in the United States. Clin Infect Dis 2004;38:805-11. 4. Romer Y, Seijo AC, Crudo F, Nicholson WL, Varela-Stokes A, Lash RR, et al. Rickettsia parkeri rickettsiosis, Argentina. Emerg Infect Dis 2011;17:1169-73. 5. Paddock CD, Finley RW, Wright CS, Robinson HN, Schrodt BJ, Lane CC, et al. Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever. Clin Infect Dis 2008;47:1188-96.
Fig 1. Acute generalized exanthematous pustulosis. Erythematous, dusky plaques with desquamation and pustules over the abdomen. The patient presented with 40% body surface area involvement and progressed to 90% at time of death.
http://dx.doi.org/10.1016/j.jaad.2014.03.024
A rapidly progressive and fatal case of atypical acute generalized exanthematous pustulosis
Fig 2. Acute generalized exanthematous pustulosis. Histopathology demonstrates subcorneal pustules without evidence of epidermal necrosis. (Hematoxylin-eosin stain; original magnification: 3100.)
To the Editor: A 78-year-old African American woman with metabolic syndrome presented with skin sloughing for 2 days. She had no history of skin conditions. Twelve days before the onset of the eruption, levofloxacin and vancomycin were started for presumed pneumonia. Cultures from the oropharynx revealed methicillin-resistant Staphylococcus aureus, and the smear was without neutrophils and contained numerous epithelial cells. No other medications had been started. Initial examination revealed erythematous, dusky plaques and papules with flaccid bullae, and scattered pustules over approximately 40% of the body surface area (Fig 1). The vaginal mucosa appeared erythematous whereas the ocular and oral mucosae were clear. The initial white blood cell count was 32.8/L with an absolute neutrophil count of 28.3/L and a normal eosinophil count. Pending histopathologic examination, a clinical diagnosis of toxic epidermal necrolysis (TEN) was
made, and intravenous immunoglobulin was started at 1 g/kg/d. Antibiotics were discontinued. After 24 hours and 1 dose of intravenous immunoglobulin, the patient progressed to diffuse epidermal sloughing with erosions of the oral mucosa and signs of shock. Intravenous immunoglobulin was discontinued because of concern for sepsis or anaphylaxis, and daptomycin, piperacillintazobactam, and fluconazole were started, along with stress-dose steroids. Skin biopsy specimen from an area of dusky erythema and pustules demonstrated subcorneal pustules without epidermal necrosis or interface alteration (Fig 2). Direct immunofluorescence, periodic acideSchiff and Gram stains, and pustule culture revealed negative findings. The patient developed multiorgan failure and disseminated intravascular coagulation, and died on hospital day 4. Her final cause of death at autopsy
Letters e87
VOLUME 71, NUMBER 3
Medicine,d Medical University of South Carolina, Charleston Funding sources: None. Conflicts of interest: None declared.
Fig 1. Primary aggressive CD81 cytotoxic T-cell (Berti) lymphoma following adalimumab. Extremity with papulosquamous plaques clinically suggestive of psoriasis.
Fig 2. Biopsy of an ulcer on the chest exhibited an epidermotropic CD81 infiltrate of atypical T-cells. (Hematoxylin-eosin stain; original magnification 310.)
lymphomas after TNF-alpha blockade has been reported.4,5 TNF-alpha blockade likely inhibits both innate and acquired immunity and may compromise immune surveillance for malignancy.5 The relation between our patient’s dermatitis and her Berti lymphoma is unclear. Her dermatitis may have represented a smoldering CTCL that transformed into Berti lymphoma, or the latter may have developed anew in the setting of immunosuppression. This case suggests that corticosteroid-refractory, histologically nonspecific dermatitis should be evaluated carefully and managed cautiously. Not all psoriasiform dermatitis is psoriasis or is safely treated as such. A high suspicion for possible CTCL and a low threshold for repeat biopsies to establish a diagnosis should be maintained when considering immunomodulatory therapy. Sarah M. Jacks, BA,a Brent R. Taylor, MD,b Raford P. Rogers III, MD,c Jonathan S. Ralston, MD,d John S. Metcalf, MD,d and John Lazarchick, MDd School of Medicinea and Department of Dermatology and Dermatologic Surgery,b Medical University of South Carolina, Charleston; Athens Regional Pathology Associates,c Georgia; Department of Pathology and Laboratory
Correspondence to: Brent R. Taylor, MD, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, 135th Rutledge Avenue, Charleston, South Carolina 29425 E-mail: [email protected] REFERENCES 1. Willemze R, Meijer CJ. Classification of cutaneous T-cell lymphoma: From Alibert to WHO-EORTC. J Cutan Pathol 2006;33(1 Suppl):18-26. 2. Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al. WHO-EORTC classification for cutaneous lymphomas. Blood 2005;105:3768. 3. Berti E, Tomasini D, Vermeer MH, Meijer CJ, Alessi E, Willemze R. Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas: a distinct clinicopathological entity with an aggressive clinical behavior. Am J Pathol 1999;155:483-92. 4. Dalle S, Balme B, Berger F, Hayett S, Thomas L. Mycosis fungoides-associated follicular mucinosis under adalimumab. Br J Dermatol 2005;153:207-8. 5. Adams AE, Zwicker J, Curiel C, Kadin ME, Falchuk KR, Drews R, et al. Aggressive cutaneous T-cell lymphomas after TNFalpha blockade. J Am Acad Dermatol 2004;51:660-2. http://dx.doi.org/10.1016/j.jaad.2014.03.022
Rickettsia parkeri: Eschar diagnosis To the Editor: A 30-year-old Caucasian woman presented to the emergency department in June with a 5-day history of flu-like symptoms. She denied recent travel from her residence, Columbiana, Alabama. She was in her usual state of health until she experienced a tick bite on her forearm 7 days before admission. Following tick removal, she noticed fatigue, myalgias, arthralgias, and severe headache, with retro-orbital pain. A temperature up to 1058F recalcitrant to antipyretics accompanied her symptoms. On examination, the patient was febrile with a temperature of 105.78F. Although she was hemodynamically stable, notable laboratory results included thrombocytopenia ( platelets: 133,000 109/L). No maculopapular rash was noted. An ulcerated nodule with a central eschar was noted on her right forearm (Fig 1). The eschar was biopsied by punch technique with half of the specimen processed routinely, while the other half was snap frozen in liquid nitrogen and sent to the Centers for Disease Control and Prevention (CDC) for further study.
e88 Letters
Fig 1. Rickettsia parkeri infection. Clinical image of cutaneous lesion on right forearm. Ulcerated nodule with central eschar.
Fig 2. Rickettsia parkeri infection. Histopathology of cutaneous punch biopsy of eschar. A nodular and diffuse lymphoid infiltrate permeates the superficial and deep dermis and extends focally into the subcutaneous fat. There is overlying ulcer and crust with associated necrosis extending to the mid dermis. (Hematoxylin-eosin stain; original magnification: 320.) Inset: Small to medium sized vessel with lymphocytic vasculitis showing endothelial swelling and fibrin thrombi (arrowhead ) and perineural inflammation (arrow). (Hematoxylin-eosin stain; original magnification: 3200.)
Histopathologic section study demonstrated a marked lymphocytic vasculitis with associated ulcer and dermal necrosis (Fig 2). Polymerase chain reaction (PCR)-based testing performed at the CDC was positive for spotted fever group rickettsiae. Gene sequencing confirmed presence of Rickettsia parkeri. The patient’s blood cultures were negative, as was serologic study for Borrelia burgdorferi and
J AM ACAD DERMATOL
SEPTEMBER 2014
Ehrlichia chaffeensis antibodies. No serologic tests for rickettsial organisms were obtained by primary team. Treatment in the emergency department included fluids and doxycycline. She was afebrile after 3 days on doxycycline and was discharged home with a 17-day course of doxycycline. She recovered without sequelae. Rickettsia parkeri is a spotted fever group rickettsia first documented in 2004 to cause human infection.1-3 Rickettsia parkeri infections in the United States and South America are a clinical rarity, with 27 cases having been reported in the English literature.1,4 Other spotted fever group rickettsiae include Rickettsia felis, Rickettsia 364D, and Rickettsia massiliae. Documented cases reveal a disease that is milder than classically described Rocky Mountain spotted fever: typical symptoms include local lymphadenopathy, fever, headache, myalgias, inoculation eschar, and a maculopapular exanthem.5 While patients with Rocky Mountain spotted fever rarely present with eschars, R. parkeri has been confused with Rickettsia akari, a mite-borne causative agent of eschar-associated rickettsialpox. Even though most American cases of rickettsialpox have occurred in inner city areas of northeastern states, recent cases have been reported in areas endemic to R. parkeri, such as rural North Carolina.5 Once the broad differential diagnosis of the febrile patient presenting with eschar has been narrowed down to the spotted fever group, diagnostic difficulty remains in obtaining a speciesspecific diagnosis. In traditional serologic assays, antibodies generated to R. parkeri antigens can cross-react with those of R. rickettsia and R. akari.5 While serology can define a diagnosis in select cases, an accurate species-specific diagnosis can be made by sending fresh skin biopsy specimens of the eschar and rash lesions to an appropriate reference laboratory for PCR or culture-based assays.1,5 Based on the literature, we suggest quantitative real-time PCR targeting the R. parkeri species-specific Rpark using DNA extracted from eschar specimens to be the gold standard for diagnosis.1,2 We are indebted to the University of Alabama at Birmingham Department of Medicine, Division of Infectious Diseases, and Department of Dermatology for their administrative support.
Nadine M. Kaskas, BS,a Johnathan J. Ledet, MD,b Alexander Wong, MD,b Christina A. Muzny, MD,c Latesha Elopre, MD,c and Lauren Hughey, MDb Louisiana State University Health School of Medicine, Shreveporta; Department of Dermatologyb
J AM ACAD DERMATOL VOLUME 71, NUMBER 3
Letters e89
and Department of Medicine, Division of Infectious Diseases,c University of Alabama, Birmingham Funding sources: None. Conflicts of interest: None declared. Correspondence to: Nadine M. Kaskas, BS, Box 253, Louisiana State University Health School of Medicine, Shreveport, LA 71103 E-mail: [email protected] REFERENCES 1. Myers T, Lalani T, Dent M, Jiang J, Daly PL, Maguire JD, et al. Detecting Rickettsia parkeri infection from eschar swab specimens. Emerg Infect Dis 2013;19:778-80. 2. Paddock CD, Fournier PE, Sumner JW, Goddard J, Elshenawy Y, Metcalfe MG, et al. Isolation of Rickettsia parkeri and identification of a novel spotted fever group Rickettsia sp from Gulf Coast ticks (Amblyomma maculatum) in the United States. Appl Environ Microbiol 2010;76:2689-96. 3. Paddock CD, Sumner JW, Comer JA, Zaki SR, Goldsmith CS, Goddard J, et al. Rickettsia parkeri: a newly recognized cause of spotted fever rickettsiosis in the United States. Clin Infect Dis 2004;38:805-11. 4. Romer Y, Seijo AC, Crudo F, Nicholson WL, Varela-Stokes A, Lash RR, et al. Rickettsia parkeri rickettsiosis, Argentina. Emerg Infect Dis 2011;17:1169-73. 5. Paddock CD, Finley RW, Wright CS, Robinson HN, Schrodt BJ, Lane CC, et al. Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever. Clin Infect Dis 2008;47:1188-96.
Fig 1. Acute generalized exanthematous pustulosis. Erythematous, dusky plaques with desquamation and pustules over the abdomen. The patient presented with 40% body surface area involvement and progressed to 90% at time of death.
http://dx.doi.org/10.1016/j.jaad.2014.03.024
A rapidly progressive and fatal case of atypical acute generalized exanthematous pustulosis
Fig 2. Acute generalized exanthematous pustulosis. Histopathology demonstrates subcorneal pustules without evidence of epidermal necrosis. (Hematoxylin-eosin stain; original magnification: 3100.)
To the Editor: A 78-year-old African American woman with metabolic syndrome presented with skin sloughing for 2 days. She had no history of skin conditions. Twelve days before the onset of the eruption, levofloxacin and vancomycin were started for presumed pneumonia. Cultures from the oropharynx revealed methicillin-resistant Staphylococcus aureus, and the smear was without neutrophils and contained numerous epithelial cells. No other medications had been started. Initial examination revealed erythematous, dusky plaques and papules with flaccid bullae, and scattered pustules over approximately 40% of the body surface area (Fig 1). The vaginal mucosa appeared erythematous whereas the ocular and oral mucosae were clear. The initial white blood cell count was 32.8/L with an absolute neutrophil count of 28.3/L and a normal eosinophil count. Pending histopathologic examination, a clinical diagnosis of toxic epidermal necrolysis (TEN) was
made, and intravenous immunoglobulin was started at 1 g/kg/d. Antibiotics were discontinued. After 24 hours and 1 dose of intravenous immunoglobulin, the patient progressed to diffuse epidermal sloughing with erosions of the oral mucosa and signs of shock. Intravenous immunoglobulin was discontinued because of concern for sepsis or anaphylaxis, and daptomycin, piperacillintazobactam, and fluconazole were started, along with stress-dose steroids. Skin biopsy specimen from an area of dusky erythema and pustules demonstrated subcorneal pustules without epidermal necrosis or interface alteration (Fig 2). Direct immunofluorescence, periodic acideSchiff and Gram stains, and pustule culture revealed negative findings. The patient developed multiorgan failure and disseminated intravascular coagulation, and died on hospital day 4. Her final cause of death at autopsy
