EXTRAORDINARY CASE REPORT
Staphylococcal Purpura Fulminans: Report of a Case Hedieh Honarpisheh, MSc, MD,* Robert Camp, MD, PhD,* and Rossitza Lazova, MD†
Abstract: Purpura fulminans (PF) is associated with several infections and most commonly with meningococcemia. However, there are only a few reports of this entity in association with toxic shock syndrome toxin-1–producing Staphylococcus aureus. We report a 53-year-old man who presented with fever, progressive hemodynamic instability, multiorgan failure, and thrombocytopenia following lobectomy for a solitary lung metastasis from rectal adenocarcinoma. He developed progressive generalized eruption of nonblanching red, purple, and black macules, papules, and plaques on the trunk and extremities consistent with PF. He died on postadmission day 3. Autopsy examination revealed purulent pleural exudate, which grew toxic shock syndrome toxin-1–producing S. aureus. Premortem and autopsy skin biopsies demonstrated epidermal necrosis, subepidermal bullae, and fibrin thrombi within small cutaneous vessels with minimal perivascular lymphocytic inflammation and without accompanying vasculitis. With this case report, we would like to draw attention to the fact that staphylococcal toxic shock syndrome–associated PF may be highly underrecognized and much more common than reflected in the literature. Key Words: purpura fulminans, staphylococcal infection, disseminated intravascular coagulation (Am J Dermatopathol 2015;37:643–646)
INTRODUCTION Purpura fulminans (PF) is a life-threatening condition characterized by hemorrhagic infarction of the skin due to disseminated intravascular coagulation and dermal vascular thrombosis. PF can present as 3 different types: (1) “neonatal PF,” which is associated with a hereditary deficiency of the anticoagulants protein C, protein S, and antithrombin III; (2) “idiopathic PF,” which is associated with an initiating febrile illness; however, deficiency of protein S is considered to be central to the pathogenesis; and (3) the most common type, “sepsis-associated PF,” which may be seen with different infections but is commonly associated with meningococcemia (10%–20% of meningococcemia cases) and less frequently with groups A and B b-hemolytic streptococci, Streptococcus pneumoniae, and Haemophilus influenzae.1 Sepsis-associated PF has a high mortality rate and includes 4 primary features: From the *Department of Pathology; and †Department of Dermatology and Pathology, Smilow Cancer Center, Yale School of Medicine, New Haven, CT. The authors declare no conflicts of interest. Reprints: Hedieh Honarpisheh, MSc, MD, Department of Pathology, EP 612-A, 310 Cedar Street, Yale New Haven Hospital, New Haven, CT 06510-3218 (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Am J Dermatopathol Volume 37, Number 8, August 2015
large, purpuric skin lesions, fever, hypotension, and disseminated intravascular coagulation.2,3
CASE REPORT The patient was a 53-year-old man with a history of moderately differentiated adenocarcinoma of the rectum, status post chemo/radiotherapy. Following detection of metastatic rectal adenocarcinoma in the lung (solitary nodule of 2.7 cm), he underwent a right lung middle lobectomy. Due to a persistent air leak, he was discharged with a right chest tube in place. Seven days later, he was brought to the emergency department in shock, febrile, and unresponsive. Several red and/or purple skin patches in the groin area were discovered on admission. He rapidly decompensated and was intubated and admitted in the intensive care unit. The patient was put on vasopressor agents and broad-spectrum antibiotics. Despite treatment, he developed acute renal failure and lactic acidosis and showed signs of shock liver, profound coagulopathy, and thrombocytopenia. On hospital day 2, he began developing diffuse, bright red macules and plaques (0.2–3.0 cm) covering his entire body, including his genitalia. These areas then became flat and dark purple and began to slough. His skin lesions were consistent with PF (Fig. 1). Laboratory data showed marked leukocytosis and left shift suggesting an infection; however, all cultures were negative until that point. Due to severely deteriorating condition of the patient, massive tissue destruction and shock, in the setting of stage IV cancer, the family opted for comfort care, and the patient passed away. At autopsy, gross examination of the lungs revealed yellow gelatinous and fibrinous exudates overlying the surface of both lungs and bilateral pleural effusion (Fig. 2A). Histologic examination of the lungs showed fibrin thrombi within small vessels of both lungs, indicative of disseminated intravascular coagulopathy (DIC) (Fig. 2B). Cultures of pleural fluid and the exudates grew Staphylococcus aureus. In addition, assay of these cultures showed toxic shock syndrome toxin-1 (TSST-1) producing S. aureus. Ecchymoses and numerous petechial, purpuric, and bullous lesions covered his skin. Premortem and autopsy skin biopsies demonstrated subcorneal and subepidermal bullae, epidermal necrosis, and fibrin deposition within small cutaneous vessels with minimal lymphocytic inflammatory infiltrate. Vasculitis was not present. There were changes consistent with DIC and PF (Figs. 3, 4). There was a thrombus (3 · 2.5 cm) within the right atrium, adherent to the wall (Fig. 5A). Histologic examination of the thrombus revealed laminar architecture with lines of Zahn, which suggested recent thrombogenesis superimposed on a probably preexisting old thrombus, possibly weeks to months old (Fig. 5B). The etiology of the thrombus was unknown, but it was likely due to the hypercoagulability associated with metastatic adenocarcinoma, recent surgery, and DIC.4 No bacteria or tumor cells were identified within the body of the thrombus. Gross examination of the rectum showed an ill-defined, fibrotic stricture involving the muscular layer. Histologic examination of the rectum revealed only focal residual adenocarcinoma with radiation effect. www.amjdermatopathology.com |
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Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 8, August 2015
Honarpisheh et al
FIGURE 1. Diffuse bright red papules and plaques on extremities and torso (upper). Older lesions were flat and dark purple and began to slough (lower). Brown dusky areas represent necrotic epidermis (lower left).
FIGURE 2. A, Yellow gelatinous and fibrinous exudates were overlying the surface of both lungs. B, Histologic examination of the lung showed numerous fibrin thrombi within small vessels of both lungs, indicative of disseminated intravascular coagulopathy. Gram stain for bacteria was negative.
DISCUSSION PF is an acute illness typically characterized by DIC and purpuric skin lesions. PF usually occurs in association with severe meningococcemia; however, meningococcal infections are relatively rare. S. aureus bacteremia, on the other hand, occurs much more frequently than meningococcemia. Because S. aureus bacteremia is not categorized as a notifiable disease by the Centers for Disease Control and Prevention, precise data on its incidence are not available. S. aureus infections have been rarely complicated by PF. Kravitz et al5 reported the first 5 cases of toxic shock syndrome (TSS)–associated PF due to S. aureus strains that produced high levels of the superantigens TSST-1, staphylococcal enterotoxin serotype B, or staphylococcal enterotoxin serotype C. TSS is a systemic and rapidly progressive illness caused by toxigenic strains of S. aureus and group A Streptococcus. TSS was first described by Todd et al6 in children aged 8 to 17 years in association with noninvasive S. aureus infection. During the early 1980s, TSS ignited widespread attention after significant number of staphylococcal TSS was reported in young menstruating women using high-absorbency tampons.7,8 Staphylococcal TSS is divided into menstrual (mTSS) and nonmenstrual (nmTSS). More than 99% of mTSS have been
FIGURE 3. Premortem skin biopsy (day 2 postadmission) demonstrated extensive hemorrhage in the papillary dermis, subcorneal splitting, thrombi within small vessels, and a mild perivascular lymphocytic infiltrate. There was no evidence of vasculitis.
644
Copyright 2014 Wolters Kluwer Health, Inc. All rights reserved.
| www.amjdermatopathology.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 8, August 2015
Staphylococcal Purpura Fulminans
TABLE 1. Diagnostic Criteria for Toxic Shock Syndrome by Centers for Disease Control and Prevention, 2011
FIGURE 4. Postmortem skin biopsy (day 3 postadmission) showed similar findings, which progressed to epidermal necrosis and formation of subepidermal bullae.
Clinical criteria for diagnosis Fever: temperature greater than or equal to 102.08F (greater than or equal to 38.98C) Rash: diffuse macular erythroderma Desquamation: 1–2 weeks after the onset of rash Hypotension: systolic blood pressure less than or equal to 90 mm Hg for adults or less than fifth percentile by age for children younger than 16 yrs Multisystem involvement (3 or more of the following organ systems) Gastrointestinal: vomiting or diarrhea at the onset of illness Muscular: severe myalgia or creatine phosphokinase level at least twice the upper limit of normal Renal: blood urea nitrogen or creatinine at least twice the upper limit of normal for laboratory or urinary sediment with pyuria (greater than or equal to 5 leukocytes per high-power field) in the absence of urinary tract infection Hepatic: total bilirubin, alanine aminotransferase enzyme, or aspartate aminotransferase enzyme levels at least twice the upper limit of normal for laboratory Hematologic: platelets less than 100,000/mm3 Central nervous system: disorientation or alterations in consciousness without focal neurologic signs when fever and hypotension are absent Laboratory criteria for diagnosis Negative results on the following tests, if obtained: Blood or cerebrospinal fluid cultures; blood culture may be positive for S. aureus Negative serologies for Rocky Mountain spotted fever, leptospirosis, or measles Case classification Probable A case that meets the laboratory criteria and in which 4 of the 5 clinical criteria described above are present Confirmed A case that meets the laboratory criteria and in which all 5 of the clinical criteria described above are present, including desquamation, unless the patient dies before desquamation occurs Data adapted from CDC. Case definitions for public health surveillance MMWR Morb Mortal Wkly Rep. 1990;39(RR-13):1. CDC. Case definitions for infectious conditions under public health surveillance. MMWR Morb Mortal Wkly Rep. 1997;46(RR10):39.
FIGURE 5. A, Large thrombus (3 · 2.5 cm) adherent to the endocardial surface of the right atrium. B, Histopathologic examination of the thrombus revealed laminar architecture with fibrotic base and “lines of Zahn” alternating with layers of polymorphonuclear leukocytes and platelets. Copyright 2014 Wolters Kluwer Health, Inc. All rights reserved.
associated with tampon usage, which has shown significant decline due to increase in public awareness; nmTSS can be seen even in the setting of trivial appearing staphylococcal infections, has shown no decline, and has higher mortality.9,10 Staphylococci are rarely cultured in these settings from blood but can be cultured from mucosal sites or localized abscesses. Almost all cases of mTSS are due to strains of S. aureus that produce TSST-1, whereas nmTSS are caused by strains producing either TSST-1 or staphylococcal enterotoxin serotype B or C.7 These toxins are capable of functioning as superantigens by attaching outside antigen-binding cleft to class II major histocompatibility complex molecules on antigen-presenting cells.11 This results in an unusual nonantigen-specific activation of T cells expressing a particular variable B sequence.12 This clonal activation of T cells subsequently leads to massive release of cytokines by both macrophages (interleukin-1b and tumor necrosis factor-a) and T cells (interleukin-2, www.amjdermatopathology.com |
645
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 8, August 2015
Honarpisheh et al
interferon-g, and tumor necrosis factor-b).11,13 These cytokines generate capillary leakage manifesting as TSS with hypotension, multiorgan failure, shock, and death. Some authors believe that superantigens are also responsible for other skin conditions, such as Kawasaki disease, psoriasis, atopic dermatitis, and cutaneous T-cell lymphoma.12 Clinical and laboratory criteria for the diagnosis of TSS, as defined by the Centers for Disease Control and Prevention, are listed in Table 1. The most important entities included in the differential diagnosis of TSS are leptospirosis, Lyme disease, meningococcemia, osteomyelitis, pelvic inflammatory disease, Rocky Mountain spotted fever, and septic shock.9 A strong suspicion, early recognition, and aggressive management may decrease overall morbidity and mortality.14 Here, we present a case of PF associated with TSS. We believe that such cases may be highly underrecognized and much more common than reflected in the literature. Early diagnosis and appropriate treatment are crucial in saving lives. REFERENCES 1. Adcock DM, Brozna J, Marlar RA. Proposed classification and pathologic mechanisms of purpura fulminans and skin necrosis. Semin Thromb Hemost. 1990;16:333–340.
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| www.amjdermatopathology.com
2. Silversides JA, Lappin E, Ferguson AJ. Staphylococcal toxic shock syndrome: mechanisms and management. Curr Infect Dis Rep. 2010;12: 392–400. 3. Gamper G, Oschatz E, Herkner H, et al. Sepsis-associated purpura fulminans in adults. Wien Klin Wochenschr. 2001;113:107–112. 4. Asopa S, Patel A, Khan OA, et al. Non-bacterial thrombotic endocarditis. Eur J Cardiothorac Surg. 2007;32:696–701. 5. Kravitz GR, Dries DJ, Peterson ML, et al. Purpura fulminans due to Staphylococcus aureus. Clin Infect Dis. 2005;40:941–947. 6. Todd J, Fishaut M, Kapral F, et al. Toxic-shock syndrome associated with phage-group-I staphylococci. Lancet. 1978;2:1116–1118. 7. Davis JP, Chesney PJ, Wand PJ, et al. Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention. N Engl J Med. 1980;303:1429–1435. 8. Osterholm MT, Davis JP, Gibson RW, et al. Toxic shock syndrome: relation to catamenial products, personal health and hygiene, and sexual practices. Ann Intern Med. 1982;96:954–958. 9. Herzer CM. Toxic shock syndrome: broadening the differential diagnosis. J Am Board Fam Pract. 2001;14:131–136. 10. DeVries AS, Lesher L, Schlievert PM, et al. Staphylococcal toxic shock syndrome 2000-2006: epidemiology, clinical features, and molecular characteristics. PLoS One. 2011;6:e22997. 11. Kotzin BL, Leung DY, Kappler J, et al. Superantigens and their potential role in human disease. Adv Immunol. 1993;54:99–166. 12. Macias ES, Pereira FA, Rietkerk W, et al. Superantigens in dermatology. J Am Acad Dermatol. 2011;64:455–472; quiz 473–474. 13. Marrack P, Kappler J. The staphylococcal enterotoxins and their relatives. Science. 1990;248:705–711. 14. Murray RJ. Recognition and management of Staphylococcus aureus toxin-mediated disease. Intern Med J. 2005;35(suppl 2):S106–S119.
Copyright 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Staphylococcal Purpura Fulminans: Report of a Case Hedieh Honarpisheh, MSc, MD,* Robert Camp, MD, PhD,* and Rossitza Lazova, MD†
Abstract: Purpura fulminans (PF) is associated with several infections and most commonly with meningococcemia. However, there are only a few reports of this entity in association with toxic shock syndrome toxin-1–producing Staphylococcus aureus. We report a 53-year-old man who presented with fever, progressive hemodynamic instability, multiorgan failure, and thrombocytopenia following lobectomy for a solitary lung metastasis from rectal adenocarcinoma. He developed progressive generalized eruption of nonblanching red, purple, and black macules, papules, and plaques on the trunk and extremities consistent with PF. He died on postadmission day 3. Autopsy examination revealed purulent pleural exudate, which grew toxic shock syndrome toxin-1–producing S. aureus. Premortem and autopsy skin biopsies demonstrated epidermal necrosis, subepidermal bullae, and fibrin thrombi within small cutaneous vessels with minimal perivascular lymphocytic inflammation and without accompanying vasculitis. With this case report, we would like to draw attention to the fact that staphylococcal toxic shock syndrome–associated PF may be highly underrecognized and much more common than reflected in the literature. Key Words: purpura fulminans, staphylococcal infection, disseminated intravascular coagulation (Am J Dermatopathol 2015;37:643–646)
INTRODUCTION Purpura fulminans (PF) is a life-threatening condition characterized by hemorrhagic infarction of the skin due to disseminated intravascular coagulation and dermal vascular thrombosis. PF can present as 3 different types: (1) “neonatal PF,” which is associated with a hereditary deficiency of the anticoagulants protein C, protein S, and antithrombin III; (2) “idiopathic PF,” which is associated with an initiating febrile illness; however, deficiency of protein S is considered to be central to the pathogenesis; and (3) the most common type, “sepsis-associated PF,” which may be seen with different infections but is commonly associated with meningococcemia (10%–20% of meningococcemia cases) and less frequently with groups A and B b-hemolytic streptococci, Streptococcus pneumoniae, and Haemophilus influenzae.1 Sepsis-associated PF has a high mortality rate and includes 4 primary features: From the *Department of Pathology; and †Department of Dermatology and Pathology, Smilow Cancer Center, Yale School of Medicine, New Haven, CT. The authors declare no conflicts of interest. Reprints: Hedieh Honarpisheh, MSc, MD, Department of Pathology, EP 612-A, 310 Cedar Street, Yale New Haven Hospital, New Haven, CT 06510-3218 (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Am J Dermatopathol Volume 37, Number 8, August 2015
large, purpuric skin lesions, fever, hypotension, and disseminated intravascular coagulation.2,3
CASE REPORT The patient was a 53-year-old man with a history of moderately differentiated adenocarcinoma of the rectum, status post chemo/radiotherapy. Following detection of metastatic rectal adenocarcinoma in the lung (solitary nodule of 2.7 cm), he underwent a right lung middle lobectomy. Due to a persistent air leak, he was discharged with a right chest tube in place. Seven days later, he was brought to the emergency department in shock, febrile, and unresponsive. Several red and/or purple skin patches in the groin area were discovered on admission. He rapidly decompensated and was intubated and admitted in the intensive care unit. The patient was put on vasopressor agents and broad-spectrum antibiotics. Despite treatment, he developed acute renal failure and lactic acidosis and showed signs of shock liver, profound coagulopathy, and thrombocytopenia. On hospital day 2, he began developing diffuse, bright red macules and plaques (0.2–3.0 cm) covering his entire body, including his genitalia. These areas then became flat and dark purple and began to slough. His skin lesions were consistent with PF (Fig. 1). Laboratory data showed marked leukocytosis and left shift suggesting an infection; however, all cultures were negative until that point. Due to severely deteriorating condition of the patient, massive tissue destruction and shock, in the setting of stage IV cancer, the family opted for comfort care, and the patient passed away. At autopsy, gross examination of the lungs revealed yellow gelatinous and fibrinous exudates overlying the surface of both lungs and bilateral pleural effusion (Fig. 2A). Histologic examination of the lungs showed fibrin thrombi within small vessels of both lungs, indicative of disseminated intravascular coagulopathy (DIC) (Fig. 2B). Cultures of pleural fluid and the exudates grew Staphylococcus aureus. In addition, assay of these cultures showed toxic shock syndrome toxin-1 (TSST-1) producing S. aureus. Ecchymoses and numerous petechial, purpuric, and bullous lesions covered his skin. Premortem and autopsy skin biopsies demonstrated subcorneal and subepidermal bullae, epidermal necrosis, and fibrin deposition within small cutaneous vessels with minimal lymphocytic inflammatory infiltrate. Vasculitis was not present. There were changes consistent with DIC and PF (Figs. 3, 4). There was a thrombus (3 · 2.5 cm) within the right atrium, adherent to the wall (Fig. 5A). Histologic examination of the thrombus revealed laminar architecture with lines of Zahn, which suggested recent thrombogenesis superimposed on a probably preexisting old thrombus, possibly weeks to months old (Fig. 5B). The etiology of the thrombus was unknown, but it was likely due to the hypercoagulability associated with metastatic adenocarcinoma, recent surgery, and DIC.4 No bacteria or tumor cells were identified within the body of the thrombus. Gross examination of the rectum showed an ill-defined, fibrotic stricture involving the muscular layer. Histologic examination of the rectum revealed only focal residual adenocarcinoma with radiation effect. www.amjdermatopathology.com |
643
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 8, August 2015
Honarpisheh et al
FIGURE 1. Diffuse bright red papules and plaques on extremities and torso (upper). Older lesions were flat and dark purple and began to slough (lower). Brown dusky areas represent necrotic epidermis (lower left).
FIGURE 2. A, Yellow gelatinous and fibrinous exudates were overlying the surface of both lungs. B, Histologic examination of the lung showed numerous fibrin thrombi within small vessels of both lungs, indicative of disseminated intravascular coagulopathy. Gram stain for bacteria was negative.
DISCUSSION PF is an acute illness typically characterized by DIC and purpuric skin lesions. PF usually occurs in association with severe meningococcemia; however, meningococcal infections are relatively rare. S. aureus bacteremia, on the other hand, occurs much more frequently than meningococcemia. Because S. aureus bacteremia is not categorized as a notifiable disease by the Centers for Disease Control and Prevention, precise data on its incidence are not available. S. aureus infections have been rarely complicated by PF. Kravitz et al5 reported the first 5 cases of toxic shock syndrome (TSS)–associated PF due to S. aureus strains that produced high levels of the superantigens TSST-1, staphylococcal enterotoxin serotype B, or staphylococcal enterotoxin serotype C. TSS is a systemic and rapidly progressive illness caused by toxigenic strains of S. aureus and group A Streptococcus. TSS was first described by Todd et al6 in children aged 8 to 17 years in association with noninvasive S. aureus infection. During the early 1980s, TSS ignited widespread attention after significant number of staphylococcal TSS was reported in young menstruating women using high-absorbency tampons.7,8 Staphylococcal TSS is divided into menstrual (mTSS) and nonmenstrual (nmTSS). More than 99% of mTSS have been
FIGURE 3. Premortem skin biopsy (day 2 postadmission) demonstrated extensive hemorrhage in the papillary dermis, subcorneal splitting, thrombi within small vessels, and a mild perivascular lymphocytic infiltrate. There was no evidence of vasculitis.
644
Copyright 2014 Wolters Kluwer Health, Inc. All rights reserved.
| www.amjdermatopathology.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 8, August 2015
Staphylococcal Purpura Fulminans
TABLE 1. Diagnostic Criteria for Toxic Shock Syndrome by Centers for Disease Control and Prevention, 2011
FIGURE 4. Postmortem skin biopsy (day 3 postadmission) showed similar findings, which progressed to epidermal necrosis and formation of subepidermal bullae.
Clinical criteria for diagnosis Fever: temperature greater than or equal to 102.08F (greater than or equal to 38.98C) Rash: diffuse macular erythroderma Desquamation: 1–2 weeks after the onset of rash Hypotension: systolic blood pressure less than or equal to 90 mm Hg for adults or less than fifth percentile by age for children younger than 16 yrs Multisystem involvement (3 or more of the following organ systems) Gastrointestinal: vomiting or diarrhea at the onset of illness Muscular: severe myalgia or creatine phosphokinase level at least twice the upper limit of normal Renal: blood urea nitrogen or creatinine at least twice the upper limit of normal for laboratory or urinary sediment with pyuria (greater than or equal to 5 leukocytes per high-power field) in the absence of urinary tract infection Hepatic: total bilirubin, alanine aminotransferase enzyme, or aspartate aminotransferase enzyme levels at least twice the upper limit of normal for laboratory Hematologic: platelets less than 100,000/mm3 Central nervous system: disorientation or alterations in consciousness without focal neurologic signs when fever and hypotension are absent Laboratory criteria for diagnosis Negative results on the following tests, if obtained: Blood or cerebrospinal fluid cultures; blood culture may be positive for S. aureus Negative serologies for Rocky Mountain spotted fever, leptospirosis, or measles Case classification Probable A case that meets the laboratory criteria and in which 4 of the 5 clinical criteria described above are present Confirmed A case that meets the laboratory criteria and in which all 5 of the clinical criteria described above are present, including desquamation, unless the patient dies before desquamation occurs Data adapted from CDC. Case definitions for public health surveillance MMWR Morb Mortal Wkly Rep. 1990;39(RR-13):1. CDC. Case definitions for infectious conditions under public health surveillance. MMWR Morb Mortal Wkly Rep. 1997;46(RR10):39.
FIGURE 5. A, Large thrombus (3 · 2.5 cm) adherent to the endocardial surface of the right atrium. B, Histopathologic examination of the thrombus revealed laminar architecture with fibrotic base and “lines of Zahn” alternating with layers of polymorphonuclear leukocytes and platelets. Copyright 2014 Wolters Kluwer Health, Inc. All rights reserved.
associated with tampon usage, which has shown significant decline due to increase in public awareness; nmTSS can be seen even in the setting of trivial appearing staphylococcal infections, has shown no decline, and has higher mortality.9,10 Staphylococci are rarely cultured in these settings from blood but can be cultured from mucosal sites or localized abscesses. Almost all cases of mTSS are due to strains of S. aureus that produce TSST-1, whereas nmTSS are caused by strains producing either TSST-1 or staphylococcal enterotoxin serotype B or C.7 These toxins are capable of functioning as superantigens by attaching outside antigen-binding cleft to class II major histocompatibility complex molecules on antigen-presenting cells.11 This results in an unusual nonantigen-specific activation of T cells expressing a particular variable B sequence.12 This clonal activation of T cells subsequently leads to massive release of cytokines by both macrophages (interleukin-1b and tumor necrosis factor-a) and T cells (interleukin-2, www.amjdermatopathology.com |
645
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 8, August 2015
Honarpisheh et al
interferon-g, and tumor necrosis factor-b).11,13 These cytokines generate capillary leakage manifesting as TSS with hypotension, multiorgan failure, shock, and death. Some authors believe that superantigens are also responsible for other skin conditions, such as Kawasaki disease, psoriasis, atopic dermatitis, and cutaneous T-cell lymphoma.12 Clinical and laboratory criteria for the diagnosis of TSS, as defined by the Centers for Disease Control and Prevention, are listed in Table 1. The most important entities included in the differential diagnosis of TSS are leptospirosis, Lyme disease, meningococcemia, osteomyelitis, pelvic inflammatory disease, Rocky Mountain spotted fever, and septic shock.9 A strong suspicion, early recognition, and aggressive management may decrease overall morbidity and mortality.14 Here, we present a case of PF associated with TSS. We believe that such cases may be highly underrecognized and much more common than reflected in the literature. Early diagnosis and appropriate treatment are crucial in saving lives. REFERENCES 1. Adcock DM, Brozna J, Marlar RA. Proposed classification and pathologic mechanisms of purpura fulminans and skin necrosis. Semin Thromb Hemost. 1990;16:333–340.
646
| www.amjdermatopathology.com
2. Silversides JA, Lappin E, Ferguson AJ. Staphylococcal toxic shock syndrome: mechanisms and management. Curr Infect Dis Rep. 2010;12: 392–400. 3. Gamper G, Oschatz E, Herkner H, et al. Sepsis-associated purpura fulminans in adults. Wien Klin Wochenschr. 2001;113:107–112. 4. Asopa S, Patel A, Khan OA, et al. Non-bacterial thrombotic endocarditis. Eur J Cardiothorac Surg. 2007;32:696–701. 5. Kravitz GR, Dries DJ, Peterson ML, et al. Purpura fulminans due to Staphylococcus aureus. Clin Infect Dis. 2005;40:941–947. 6. Todd J, Fishaut M, Kapral F, et al. Toxic-shock syndrome associated with phage-group-I staphylococci. Lancet. 1978;2:1116–1118. 7. Davis JP, Chesney PJ, Wand PJ, et al. Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention. N Engl J Med. 1980;303:1429–1435. 8. Osterholm MT, Davis JP, Gibson RW, et al. Toxic shock syndrome: relation to catamenial products, personal health and hygiene, and sexual practices. Ann Intern Med. 1982;96:954–958. 9. Herzer CM. Toxic shock syndrome: broadening the differential diagnosis. J Am Board Fam Pract. 2001;14:131–136. 10. DeVries AS, Lesher L, Schlievert PM, et al. Staphylococcal toxic shock syndrome 2000-2006: epidemiology, clinical features, and molecular characteristics. PLoS One. 2011;6:e22997. 11. Kotzin BL, Leung DY, Kappler J, et al. Superantigens and their potential role in human disease. Adv Immunol. 1993;54:99–166. 12. Macias ES, Pereira FA, Rietkerk W, et al. Superantigens in dermatology. J Am Acad Dermatol. 2011;64:455–472; quiz 473–474. 13. Marrack P, Kappler J. The staphylococcal enterotoxins and their relatives. Science. 1990;248:705–711. 14. Murray RJ. Recognition and management of Staphylococcus aureus toxin-mediated disease. Intern Med J. 2005;35(suppl 2):S106–S119.
Copyright 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
![[Necrosis of maxilla secondary to purpura fulminans. A case report].](/assets/img/hold.png)
