- Email: [email protected]
Ecthyma gangrenosum in the absence of pseudomonas bacteremia in a bone marrow transplant recipient
BRIEF CLINICAL
matory drugs, but there was no relief of the muscle tenderness or other symptoms. She was then treated with fluoxetine hydrochloride at a dose of 20 mglday, which was later increased to 40 mglday, and she experienced complete relief over a period of about one month. Six months of follow-up have shown no recurrence of the symptoms of fibrositis. This is the first documented report of successful treatment of fibrositis with fluoxetine hydrochloride. There have been suggestions that the sleep disturbances in fibrositis may be related to serotonin metabolism [l]. Another study also suggested that abnormal serotoninergic mechanisms were responsible for the pain of fibrositis [2]. Fluoxetine hydrochloride is known to block reuptake of serotonin in the brain. Therefore, it is not surprising that fluoxetine hydrochloride was beneficial in treating fibrositis in this case. STEVENA.GELLER,M.D. Howard County General Hospital Cotumbia, Marytand 21044 1. Moldofsky H: Sleep and musculoskeletal pain. Am J Med 1986; 81 (suppl3A): 85-89. 2. Moldofsky H. Warsh JJ: Plasma byptophan and musculoskeletal pain in non-articular rheumatism (“fibrositis syndrome”). Pain 1978: 5: 65-71. Submitted
June
22. 1989,
and accepted
July 31. 1989
ECTHYMA GANGRENOSUM IN THE ABSENCE OF PSEUDOMONAS BACTEREMIA IN A BONE MARROW TRANSPLANT RECIPIENT The association between systemic Pseudomonas aeruginosa infections and the characteristic necrotic skin lesions of ecthyma gangrenosum is well known. This bacterium, commonly isolated from hospital environments, seems to have a predilection to cause infection in patients with leukemia, severe burns, neutropenia, or organ transplant, or in those receiving immunosuppressive therapy. Lesions that appear during the course of P. aeruginosa-associated septicemia often portend a potentially life-threatening infection. However, in recent years, a number of reports have described patients with ecthyma gangrenosum who have no evidence of bacteremia and therefore have a better prognosis
[l-5]. In this article we describe such a patient with an unusual presentation of localized cutaneous pseudomonas infection, and offer several possibilities as to its origin. Case Report. A 29-year-old man who had undergone allogeneic bone marrow transplantation in 1986 for myelodysplastic syndrome was hospitalized on October 19, 1988, with chills, rigors, and a temperature of 39.4”C. He had returned from a brief Caribbean vacation two days before admission, when he noted crusting scabs on his forehead and the development of slightly painful and pruritic weeping lesions in the groin, which failed to improve after treatment with hydrogen peroxide and topical steroids. He had no history of trauma, insect or animal bites, or any hot tub exposure during his trip; however, he did recall the presence of mites in his hotel room. No one else on the trip became ill. The patient denied any other associated symptoms. Medications included cyclosporin A and penicillin VK for pneumococcal prophylaxis. Physical examination revealed a well-developed white man with an oral temperature of 38.6”C, who appeared comfortable and otherwise had normal vital signs. Several crusted, excoriated areas were noted at the hairline over both temples. The suprapubic region demonstrated multiple tender, weeping papulovesicular lesions. He had no significant adenopathy. The lungs were clear, and a grade 216 systolic murmur was appreciated at the apex. The abdomen was benign, and findings on rectal examination were nontender with heme-negative stool. The hemoglobin level was 11.9 g/ dL, the white blood cell count was 6,800/mm3 with 53% segmented neutrophils, 27% lymphocytes, 19% monocytes, and 1% eosinophils, and the platelet count was 103,000/ mm3. The erythrocyte sedimentation rate was 11 nun/hour. Liver function tests, known to demonstrate abnormal findings secondary to chronic graft-versus-host disease, revealed an alkaline phosphatase level of 773 IU/mL, lactate dehydrogenase level of 682 IU/mL, and serum glutamic oxaloacetic transaminase level of 83 IU/mL. The serum creatinine level was 1.4 mg/dL, and a chest roentgenograrn was normal. The patient was seen in consulNovember
1989
OBSERVATIONS
tation by a dermatologist, who believed the lesions to be most consistent with bullous impetigo. However, while the results of cultures of blood, urine, and skin lesions were pending, antibiotic therapy with nafcillin, cefotaxime, and acyclovir was initiated. Results of blood and urine cultures remained negative, but Staphylococcus aureus (sensitive to nafcillin) was isolated from the skin lesions. Antibiotic therapy was changed to vancomycin alone because of a question of a 8-lactaminduced cutaneous drug eruption manifested by a diffuse erythematous papular rash and peripheral eosinophilia. Viral cultures of the skin lesion failed to reveal herpes infection, and acyclovir was discontinued. Within a couple of days the rash and original skin lesions resolved, but on the seventh hospital day, the patient became febrile to 405°C and complained of new painful bullous lesions over both upper medial thighs and pubic area, with each lesion measuring approximately 1 cm in diameter. These bullae soon became hemorrhagic and developed central black eschars with surrounding erythema (Figures 1 and 2), consistent with ecthyma gangrenosum. He also noted some perirectal tenderness, although no lesions were evident. Blood cultures remained negative, but a culture of biopsy material from the new lesions grew P. aeruginosa. Antibiotics were changed to aztreonam and tobramycin, and clindamycin was added because there was concern about a perirectal process. The patient had rapid defervescence, and the lesions began to slowly resolve. An abdominal computed tomographic scan failed to reveal any perirectal collection, but Clostridium difficjle toxin was isolated from the stool, and the patient was treated with oral vancomycin. After 14 days of in-hospital therapy for his ecthyma gangrenosum, the patient was discharged to receive another two weeks of axtreonam and tobramycin via home intravenous theraPYComments. Ecthyma gangrenosum represents a vasculitis caused by direct bacterial invasion of tissue. Although the most common etiologic agent is P. aeruginosa, similar lesions have been described in infections caused by Aeromonas hydrophila, S. aureus, Serratia marcescens, Escherichia coli, and,
The American
Journal
of Medlclne
Volume
97
595
BRIEF CLINICAL
OBSERVATIONS
Figure 1. Ecthyma gangrenosum of the medial aspect of the left thigh showing black eschar with surrounding induration and erythema.
Figure 2. Cluster of necrotic lesions of the right upper thigh and perineum.
rarely, fungi [6-lo]. The lesions evolve from erythematous macules or vesicles into characteristic necrotic ulcers with black eschars, and are usually seen in immunocompromised, neutropenic patients. In most cases, P. aeruginosa can be cultured from the blood as well as from the skin lesions. However, there is increasing evidence that ecthyma gangrenosum can represent localized cutaneous eruptions that are not accompanied by systemic infection. The earliest description of such primary skin lesions was by Van den Broek et al [l] in 1979. Since then, several similar cases [2,3,5] as well as reports of ecthyma developing from pseudomonas folliculitis have been described [4]. In the lat596
November
1989
The American
Journal
ter article, the lesions initially appeared as erythematous papulopustules similar to “swimming pool folliculitis” [ll-131, but then became bullous and necrotic. In all cases, the lesions were indistinguishable from those occurring during pseudomonas septicemia and probably arose because of an impaired cellular immune response. In the patient we describe here, neutropenia was not a complicating factor, although he had been receiving cyclosporin A and therefore had immunosuppression. In the early stages the lesions appeared vesiculobullous, but later evolved to a more indurated and necrotic eruption typical of classic ecthyma gangrenosum. They were distributed over the anogenital reof Medicine
Volume
87
gion and thighs, and pseudomonas was easily isolated from cultures of ground skin tissue. Although histopathology of the necrotic lesions did not reveal classic necrotizing vasculitis with invasion of vessel walls by bacteria, this may possibly be due to biopsy sampling error. The source of infection in our patient cannot be determined with certainty, but several possibilities exist as to its origin and pathogenesis. Although it is unlikely, we cannot exclude a low-level, transient bacteremia that went undetected in blood cultures. The organisms could have originated from the gastrointestinal tract or the skin itself. A more plausible explanation is that the patient presented with impetiginized lesions (from which S.
aureus was initially isolated), which subsequently became coloi nized and superinfected with hospital-acquired P. aeruginosa and then developed into ecthyma gangrenosum. To support this theory, it was not until anti-pseudomonal therapy was begun that the patient had defervescence and exhibited a dramatic clinical response. This report confirms the observations of others who have described localized cutaneous lesions caused by pseudomonas in immunocompromised patients. However, as we point out in this case, ecthyma gangrenosum may develop even in the absence of neutropenia. The infection is most likely nosocomially acquired, underscoring the need for careful surveillance and education of hospital personnel to minimize in-hospital spread. Physicians must be aware of the spectrum of pseudomonas-induced skin lesions, as early recognition and institution of appropriate therapy can help ensure a favorable prognosis. JUDITH E. WOLF, HANS H. LIU, LINDA G. RABINO WITZ,
M.D. M.D. M.D.
Thomas Jefferson &iversitv Philadelphia, P&znsylvania ISlO? 1. Van den Broek PJ, Van der Meer JWM, Kunst MW: The pathogenesis of ecthyma gangrenosum. J Infect 1979; 1: 263-267. 2. Anderson MG: Pseudomonas septicemia and ecthyma gangrenosum. S Afr Med J 1979: 55: 504-508. 3. Hunvitz RM, Learning RD. Horine RK: Necrotic cellulitis: a localized form of septic vasculitis. Arch Dermatol 1984: 120: 87-92. 4. El Blaze P. Thyss A, Caldani C. et at Pseudomonas aeruginosa O-1 1 folliculitis: development into ecthyma gangrenosum in immunosuppressed patients. Arch Dermatol 1985; 121: 873-876. 5. Huminer D, Siegman-IgraY. MorduchowiuG, etat Ecthyma gangrenosum without bacteremia. Arch Intern Med 1987; 147: 299-301. 6. Ketover BP, Young LS. Armstrong D: Septicemia due to Aeromonas hydrophila: clinical and immunologic aspects. J Infect Dis 1973; 127: 284-290. 7. File TM, Marina OA, Flowers FP: Necrotic skin lesions associated with disseminated candidiasis. Arch Dermatol 1979; 115: 214-215. 8. Musher DM: Cutaneous and soft-tissue manifestations of sepsis due to gram-negative enteric bacilli. Rev Infect Dis 1980; 2: 854-865. 9. Fine JD. Miller JA, Harrist TJ. Haynes HA: Cutane ous lesions in disseminated candidiasis mimicking ecthyma gangrenosum. Am J Med 1981: 70: 11131135. 10. Braverman M: Infectious skin signs of systemic disease. Philadelphia: W8 Saunders, 1981; 821-825. 11. Centers for Disease Control: Outbreak of Pseudomonas aeruginosa serotype 0:9 associated witn a whirlpool. MMWR 1981; 30: 329-331. 12.Gustafson TL. Band JD. Hutcheson RH, et at. Pseudomonas folliculitis: an outbreak and review. Rev Infect Dis 1983; 5: l-8. 13. Fox AB, Hambrick GW: Recreationally associated Pseudomonas aeruginosafolliculitis: report of an epidemic Arch Dermatol 1984; 120: 13CI4-1307. Submitted
March
27, 1989,
and accepted
July 31. 1989
ANTIPHOSPHOLIPID ANTIBODIES AND SNEDDON’S SYNDROME We read with interest the article by Asherson et al (Am J Med 1989; 86: 391-399), in which the syndrome of Sneddon is considered to be linked to the so-called primary antiphospholipid syndrome. The association of livedo reticularis and cerebrovascular accidents in the absence of systemic disease is known as Sneddon’s syndrome [l]. The etiopathogenesis is unknown, although it has recently been considered a hereditary arteriopathy [2], and its association with antiphospholipid antibodies is currently the subject of discussion [3-
61.
We present five cases of Sneddon’s syndrome in which antiphospholipid antibodies were determined. The study consisted of five women aged 34 to 58 years (mean, 43 years). Their livedo reticularis was generalized, predominantly in lower limbs, and preceded neurologic signs in every case. In four subjects, established cerebrovascular lesions were produced, one multiple and one characterized by transient ischemic attacks. Three patients presented with Raynaud’s disease, one had acrocyanosis, and three had arterial hypertension. They had no history of repeated abortions, thrombi at other levels, or thrombopenia. The result of cerebral angiography was normal in two cases, while multiple occlusions and vascular stenosis with leptomeningeal anastomosis and collateral circulation were observed in three. Hand angiography was carried out in three patients, revealing fine vessels in two of them and multiple occlusions and stenosis in distal branches in the third. Cranial computed tomographic scan demonstrated cortical retraction and ventricular dilatation with areas of infarct in four cases. The result of echocardiography was normal in four subjects, whereas in one, the left atrium was dilated and the mitral area was small. Positive antinuclear antibodies were found at low titer (1:40) in two patients, with no other sign of immunologic disease. Findings on VDRL and lupus anticoagulant studies were negative. IgG+ anticardiolipin antibodies were observed in four cases (56 U/ mL, 32 U/mL, 39 U/mL, and 31 Ul mL; normal value: less than 5 U/ November
1999
The American
mL), the first three of whom presented with IgM+ (41 U/mL, 8 Ul mL, and 6 U/mL, respectively; normal value: less than 3 U/mL). One patient presented with no anticardiolipin antibodies. With antiplatelet drugs and control of aiterial hypertension, no new episodes of cerebral ischemia have occurred. However, in three cases, dementia has followed. Two patients with positive anticardiolipin antibodies each had a daughter with idiopathic livedo reticularis. The daughters did not present with cardiovascular disease, but did have IgG+ anticardiolipin antibodies (21 U/mL, 33 U/mL) . Thus, in agreement with Asherson et al (Am J Med 1989; 86: 391399), we consider that the systematic investigation of anticardiolipin antibodies in patients with Sneddon’s syndr0m.e may identify a subgroup that fulfills the criteria for primary antiphospholipid syndrome, with the consequent therapeutic implications. Moreover, the observation of anticardiolipin antibodies in two mother-daughter cases strongly suggests the intervention of genetic factors in its development. JUAN A. VARGAS, M.D. MIGUEL YEBRA, MD. MARIA L. PASCUAL, MD. LUIS MANZANO. M.D. ALBERTO DURANTEZ, M.D.,.ph.D.
Clbica Puerta de Hierro 28035 Madrid, Spain 1. Sneddon IB: Cerebrovascular lesions and livedo reticularis. Br J Dermatol 1965; 77: M-185. 2. Rebollo M. Val JF. Garijo F. Quintana F. Berciano J: Livedo reticularis and cerebrovascular lesions (Sneddon’s syndrome). Clinical. radiological and pathological features in eight cases. Brain 1983; 106: 965979. 3. Jonas J, Kblble K. Vdlcker HE, Kalden JR: Central retinal artery occlusion in Sneddon’s disease associated with antiphospholipid antibodies. Am J Ophthalmol 1986: 102: 37-40. 4.Montalban J. Ordi J. Barquinero J, Vilardell M: Sneddon’s syndrome and anticardiolipin antibodies. Stroke 1988; 19: 785-786. 5. Levine SR, Langer SL. Albers JW. Welch KMA: Sneddon’s syndrome: and antiphospholipid antibody syndrome? Neurology 1988: 38: 798-803. 6. Grattan CEH. Burton JL. Boon AP: Sneddon’s syndrome (fivedo reticularis and cerebral thrombosis) with livedo vasculitis and antfcardiolipin antibodies. Br J Dermatol 1989: 120: 441-447. Submitted
July 13.1989,
and accepted
July 20.1989
SYNCOPE WITH ABRliPT TERMINATION OF EXERCISE Sinus bradycardia and atrioventricular (AV) block are common in well-trained athletes without orJournal
of Medicine
Volume
97
597
matory drugs, but there was no relief of the muscle tenderness or other symptoms. She was then treated with fluoxetine hydrochloride at a dose of 20 mglday, which was later increased to 40 mglday, and she experienced complete relief over a period of about one month. Six months of follow-up have shown no recurrence of the symptoms of fibrositis. This is the first documented report of successful treatment of fibrositis with fluoxetine hydrochloride. There have been suggestions that the sleep disturbances in fibrositis may be related to serotonin metabolism [l]. Another study also suggested that abnormal serotoninergic mechanisms were responsible for the pain of fibrositis [2]. Fluoxetine hydrochloride is known to block reuptake of serotonin in the brain. Therefore, it is not surprising that fluoxetine hydrochloride was beneficial in treating fibrositis in this case. STEVENA.GELLER,M.D. Howard County General Hospital Cotumbia, Marytand 21044 1. Moldofsky H: Sleep and musculoskeletal pain. Am J Med 1986; 81 (suppl3A): 85-89. 2. Moldofsky H. Warsh JJ: Plasma byptophan and musculoskeletal pain in non-articular rheumatism (“fibrositis syndrome”). Pain 1978: 5: 65-71. Submitted
June
22. 1989,
and accepted
July 31. 1989
ECTHYMA GANGRENOSUM IN THE ABSENCE OF PSEUDOMONAS BACTEREMIA IN A BONE MARROW TRANSPLANT RECIPIENT The association between systemic Pseudomonas aeruginosa infections and the characteristic necrotic skin lesions of ecthyma gangrenosum is well known. This bacterium, commonly isolated from hospital environments, seems to have a predilection to cause infection in patients with leukemia, severe burns, neutropenia, or organ transplant, or in those receiving immunosuppressive therapy. Lesions that appear during the course of P. aeruginosa-associated septicemia often portend a potentially life-threatening infection. However, in recent years, a number of reports have described patients with ecthyma gangrenosum who have no evidence of bacteremia and therefore have a better prognosis
[l-5]. In this article we describe such a patient with an unusual presentation of localized cutaneous pseudomonas infection, and offer several possibilities as to its origin. Case Report. A 29-year-old man who had undergone allogeneic bone marrow transplantation in 1986 for myelodysplastic syndrome was hospitalized on October 19, 1988, with chills, rigors, and a temperature of 39.4”C. He had returned from a brief Caribbean vacation two days before admission, when he noted crusting scabs on his forehead and the development of slightly painful and pruritic weeping lesions in the groin, which failed to improve after treatment with hydrogen peroxide and topical steroids. He had no history of trauma, insect or animal bites, or any hot tub exposure during his trip; however, he did recall the presence of mites in his hotel room. No one else on the trip became ill. The patient denied any other associated symptoms. Medications included cyclosporin A and penicillin VK for pneumococcal prophylaxis. Physical examination revealed a well-developed white man with an oral temperature of 38.6”C, who appeared comfortable and otherwise had normal vital signs. Several crusted, excoriated areas were noted at the hairline over both temples. The suprapubic region demonstrated multiple tender, weeping papulovesicular lesions. He had no significant adenopathy. The lungs were clear, and a grade 216 systolic murmur was appreciated at the apex. The abdomen was benign, and findings on rectal examination were nontender with heme-negative stool. The hemoglobin level was 11.9 g/ dL, the white blood cell count was 6,800/mm3 with 53% segmented neutrophils, 27% lymphocytes, 19% monocytes, and 1% eosinophils, and the platelet count was 103,000/ mm3. The erythrocyte sedimentation rate was 11 nun/hour. Liver function tests, known to demonstrate abnormal findings secondary to chronic graft-versus-host disease, revealed an alkaline phosphatase level of 773 IU/mL, lactate dehydrogenase level of 682 IU/mL, and serum glutamic oxaloacetic transaminase level of 83 IU/mL. The serum creatinine level was 1.4 mg/dL, and a chest roentgenograrn was normal. The patient was seen in consulNovember
1989
OBSERVATIONS
tation by a dermatologist, who believed the lesions to be most consistent with bullous impetigo. However, while the results of cultures of blood, urine, and skin lesions were pending, antibiotic therapy with nafcillin, cefotaxime, and acyclovir was initiated. Results of blood and urine cultures remained negative, but Staphylococcus aureus (sensitive to nafcillin) was isolated from the skin lesions. Antibiotic therapy was changed to vancomycin alone because of a question of a 8-lactaminduced cutaneous drug eruption manifested by a diffuse erythematous papular rash and peripheral eosinophilia. Viral cultures of the skin lesion failed to reveal herpes infection, and acyclovir was discontinued. Within a couple of days the rash and original skin lesions resolved, but on the seventh hospital day, the patient became febrile to 405°C and complained of new painful bullous lesions over both upper medial thighs and pubic area, with each lesion measuring approximately 1 cm in diameter. These bullae soon became hemorrhagic and developed central black eschars with surrounding erythema (Figures 1 and 2), consistent with ecthyma gangrenosum. He also noted some perirectal tenderness, although no lesions were evident. Blood cultures remained negative, but a culture of biopsy material from the new lesions grew P. aeruginosa. Antibiotics were changed to aztreonam and tobramycin, and clindamycin was added because there was concern about a perirectal process. The patient had rapid defervescence, and the lesions began to slowly resolve. An abdominal computed tomographic scan failed to reveal any perirectal collection, but Clostridium difficjle toxin was isolated from the stool, and the patient was treated with oral vancomycin. After 14 days of in-hospital therapy for his ecthyma gangrenosum, the patient was discharged to receive another two weeks of axtreonam and tobramycin via home intravenous theraPYComments. Ecthyma gangrenosum represents a vasculitis caused by direct bacterial invasion of tissue. Although the most common etiologic agent is P. aeruginosa, similar lesions have been described in infections caused by Aeromonas hydrophila, S. aureus, Serratia marcescens, Escherichia coli, and,
The American
Journal
of Medlclne
Volume
97
595
BRIEF CLINICAL
OBSERVATIONS
Figure 1. Ecthyma gangrenosum of the medial aspect of the left thigh showing black eschar with surrounding induration and erythema.
Figure 2. Cluster of necrotic lesions of the right upper thigh and perineum.
rarely, fungi [6-lo]. The lesions evolve from erythematous macules or vesicles into characteristic necrotic ulcers with black eschars, and are usually seen in immunocompromised, neutropenic patients. In most cases, P. aeruginosa can be cultured from the blood as well as from the skin lesions. However, there is increasing evidence that ecthyma gangrenosum can represent localized cutaneous eruptions that are not accompanied by systemic infection. The earliest description of such primary skin lesions was by Van den Broek et al [l] in 1979. Since then, several similar cases [2,3,5] as well as reports of ecthyma developing from pseudomonas folliculitis have been described [4]. In the lat596
November
1989
The American
Journal
ter article, the lesions initially appeared as erythematous papulopustules similar to “swimming pool folliculitis” [ll-131, but then became bullous and necrotic. In all cases, the lesions were indistinguishable from those occurring during pseudomonas septicemia and probably arose because of an impaired cellular immune response. In the patient we describe here, neutropenia was not a complicating factor, although he had been receiving cyclosporin A and therefore had immunosuppression. In the early stages the lesions appeared vesiculobullous, but later evolved to a more indurated and necrotic eruption typical of classic ecthyma gangrenosum. They were distributed over the anogenital reof Medicine
Volume
87
gion and thighs, and pseudomonas was easily isolated from cultures of ground skin tissue. Although histopathology of the necrotic lesions did not reveal classic necrotizing vasculitis with invasion of vessel walls by bacteria, this may possibly be due to biopsy sampling error. The source of infection in our patient cannot be determined with certainty, but several possibilities exist as to its origin and pathogenesis. Although it is unlikely, we cannot exclude a low-level, transient bacteremia that went undetected in blood cultures. The organisms could have originated from the gastrointestinal tract or the skin itself. A more plausible explanation is that the patient presented with impetiginized lesions (from which S.
aureus was initially isolated), which subsequently became coloi nized and superinfected with hospital-acquired P. aeruginosa and then developed into ecthyma gangrenosum. To support this theory, it was not until anti-pseudomonal therapy was begun that the patient had defervescence and exhibited a dramatic clinical response. This report confirms the observations of others who have described localized cutaneous lesions caused by pseudomonas in immunocompromised patients. However, as we point out in this case, ecthyma gangrenosum may develop even in the absence of neutropenia. The infection is most likely nosocomially acquired, underscoring the need for careful surveillance and education of hospital personnel to minimize in-hospital spread. Physicians must be aware of the spectrum of pseudomonas-induced skin lesions, as early recognition and institution of appropriate therapy can help ensure a favorable prognosis. JUDITH E. WOLF, HANS H. LIU, LINDA G. RABINO WITZ,
M.D. M.D. M.D.
Thomas Jefferson &iversitv Philadelphia, P&znsylvania ISlO? 1. Van den Broek PJ, Van der Meer JWM, Kunst MW: The pathogenesis of ecthyma gangrenosum. J Infect 1979; 1: 263-267. 2. Anderson MG: Pseudomonas septicemia and ecthyma gangrenosum. S Afr Med J 1979: 55: 504-508. 3. Hunvitz RM, Learning RD. Horine RK: Necrotic cellulitis: a localized form of septic vasculitis. Arch Dermatol 1984: 120: 87-92. 4. El Blaze P. Thyss A, Caldani C. et at Pseudomonas aeruginosa O-1 1 folliculitis: development into ecthyma gangrenosum in immunosuppressed patients. Arch Dermatol 1985; 121: 873-876. 5. Huminer D, Siegman-IgraY. MorduchowiuG, etat Ecthyma gangrenosum without bacteremia. Arch Intern Med 1987; 147: 299-301. 6. Ketover BP, Young LS. Armstrong D: Septicemia due to Aeromonas hydrophila: clinical and immunologic aspects. J Infect Dis 1973; 127: 284-290. 7. File TM, Marina OA, Flowers FP: Necrotic skin lesions associated with disseminated candidiasis. Arch Dermatol 1979; 115: 214-215. 8. Musher DM: Cutaneous and soft-tissue manifestations of sepsis due to gram-negative enteric bacilli. Rev Infect Dis 1980; 2: 854-865. 9. Fine JD. Miller JA, Harrist TJ. Haynes HA: Cutane ous lesions in disseminated candidiasis mimicking ecthyma gangrenosum. Am J Med 1981: 70: 11131135. 10. Braverman M: Infectious skin signs of systemic disease. Philadelphia: W8 Saunders, 1981; 821-825. 11. Centers for Disease Control: Outbreak of Pseudomonas aeruginosa serotype 0:9 associated witn a whirlpool. MMWR 1981; 30: 329-331. 12.Gustafson TL. Band JD. Hutcheson RH, et at. Pseudomonas folliculitis: an outbreak and review. Rev Infect Dis 1983; 5: l-8. 13. Fox AB, Hambrick GW: Recreationally associated Pseudomonas aeruginosafolliculitis: report of an epidemic Arch Dermatol 1984; 120: 13CI4-1307. Submitted
March
27, 1989,
and accepted
July 31. 1989
ANTIPHOSPHOLIPID ANTIBODIES AND SNEDDON’S SYNDROME We read with interest the article by Asherson et al (Am J Med 1989; 86: 391-399), in which the syndrome of Sneddon is considered to be linked to the so-called primary antiphospholipid syndrome. The association of livedo reticularis and cerebrovascular accidents in the absence of systemic disease is known as Sneddon’s syndrome [l]. The etiopathogenesis is unknown, although it has recently been considered a hereditary arteriopathy [2], and its association with antiphospholipid antibodies is currently the subject of discussion [3-
61.
We present five cases of Sneddon’s syndrome in which antiphospholipid antibodies were determined. The study consisted of five women aged 34 to 58 years (mean, 43 years). Their livedo reticularis was generalized, predominantly in lower limbs, and preceded neurologic signs in every case. In four subjects, established cerebrovascular lesions were produced, one multiple and one characterized by transient ischemic attacks. Three patients presented with Raynaud’s disease, one had acrocyanosis, and three had arterial hypertension. They had no history of repeated abortions, thrombi at other levels, or thrombopenia. The result of cerebral angiography was normal in two cases, while multiple occlusions and vascular stenosis with leptomeningeal anastomosis and collateral circulation were observed in three. Hand angiography was carried out in three patients, revealing fine vessels in two of them and multiple occlusions and stenosis in distal branches in the third. Cranial computed tomographic scan demonstrated cortical retraction and ventricular dilatation with areas of infarct in four cases. The result of echocardiography was normal in four subjects, whereas in one, the left atrium was dilated and the mitral area was small. Positive antinuclear antibodies were found at low titer (1:40) in two patients, with no other sign of immunologic disease. Findings on VDRL and lupus anticoagulant studies were negative. IgG+ anticardiolipin antibodies were observed in four cases (56 U/ mL, 32 U/mL, 39 U/mL, and 31 Ul mL; normal value: less than 5 U/ November
1999
The American
mL), the first three of whom presented with IgM+ (41 U/mL, 8 Ul mL, and 6 U/mL, respectively; normal value: less than 3 U/mL). One patient presented with no anticardiolipin antibodies. With antiplatelet drugs and control of aiterial hypertension, no new episodes of cerebral ischemia have occurred. However, in three cases, dementia has followed. Two patients with positive anticardiolipin antibodies each had a daughter with idiopathic livedo reticularis. The daughters did not present with cardiovascular disease, but did have IgG+ anticardiolipin antibodies (21 U/mL, 33 U/mL) . Thus, in agreement with Asherson et al (Am J Med 1989; 86: 391399), we consider that the systematic investigation of anticardiolipin antibodies in patients with Sneddon’s syndr0m.e may identify a subgroup that fulfills the criteria for primary antiphospholipid syndrome, with the consequent therapeutic implications. Moreover, the observation of anticardiolipin antibodies in two mother-daughter cases strongly suggests the intervention of genetic factors in its development. JUAN A. VARGAS, M.D. MIGUEL YEBRA, MD. MARIA L. PASCUAL, MD. LUIS MANZANO. M.D. ALBERTO DURANTEZ, M.D.,.ph.D.
Clbica Puerta de Hierro 28035 Madrid, Spain 1. Sneddon IB: Cerebrovascular lesions and livedo reticularis. Br J Dermatol 1965; 77: M-185. 2. Rebollo M. Val JF. Garijo F. Quintana F. Berciano J: Livedo reticularis and cerebrovascular lesions (Sneddon’s syndrome). Clinical. radiological and pathological features in eight cases. Brain 1983; 106: 965979. 3. Jonas J, Kblble K. Vdlcker HE, Kalden JR: Central retinal artery occlusion in Sneddon’s disease associated with antiphospholipid antibodies. Am J Ophthalmol 1986: 102: 37-40. 4.Montalban J. Ordi J. Barquinero J, Vilardell M: Sneddon’s syndrome and anticardiolipin antibodies. Stroke 1988; 19: 785-786. 5. Levine SR, Langer SL. Albers JW. Welch KMA: Sneddon’s syndrome: and antiphospholipid antibody syndrome? Neurology 1988: 38: 798-803. 6. Grattan CEH. Burton JL. Boon AP: Sneddon’s syndrome (fivedo reticularis and cerebral thrombosis) with livedo vasculitis and antfcardiolipin antibodies. Br J Dermatol 1989: 120: 441-447. Submitted
July 13.1989,
and accepted
July 20.1989
SYNCOPE WITH ABRliPT TERMINATION OF EXERCISE Sinus bradycardia and atrioventricular (AV) block are common in well-trained athletes without orJournal
of Medicine
Volume
97
597