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Cutaneous necrosis at sites of transfusion: Cold agglutinin disease
356
Correspondence
5. Brown CF, Gallup DG, Brown VM. Hidraderftis suppurafiva of the anogenital region responsive to isotretinoin: a case report and review of the literature. [abstract]. South Med J 1986;79:9(suppl 2:23). 6. Jones DH, Cunliffe W J, King K. Hidradenitis suppurativa--laek of success with 13-cis-retinoie acid [letter]. Br J Dermatol 1982;107:252. 7. Norris JFB, Cunliffe WJ. Failure of treatment of familial widespread hidradenitis suppurativa with isotretinoin. Clin Exp Dermatol 1986;11:579-83. 8. Stewart WD, Light ML Successful treatment of hidradenitis suppurativa with etretinate. [abstract]. Dermatologica 1984;169:258. 91 Paravieini U, Camenzind M, Gower M, et al. Multiple dose pharmacokinetics of Ro 10-1670, the main metabolate of etretinate (Tigason). In: Saurat J-H, ed. Retinoids: new trends in research and therapy. New York: S Karger, 1985:289-92. 10. Goldstein JA, Socha-Szott A, Thomsen R J, Pochi PE, Shalita AR, Strauss JS. Comparative effect ofisotretinoin and etretinate on acne and sebaceous gland secretion. J AM ACAD DEgMATOL1982;6:760-5. 11. Harms M, Philippe I, Radeff B, et al. Arotinoid Ro 13-6298 and etretin: two new retinoids inferior to isotretinoin in sebum suppression and ache treatment. Acta Derm Venereol (Stoekh) 1986;66:149-54. 12. Bradshaw D, Cashin CH, Kennedy AJ. Further studies on the anti-inflammatory effects of retinoids. In: Saurat JH, ed. Retinoids: new trends in research and therapy. New York: S Karger, 1985:204-18. 13. Elias PM, Williams ML. Retinoid effects on epidermal differentiation. In: Saurat JH, ed. Refinoids: new trends in research and therapy. New York: S Karger, 1985:13858.
Cutaneous necrosis at sites of transfusion: Cold agglutinin disease To the Editor: Cutaneous manifestations associated with cold agglutinins are usually confined to reversible acrocyanosis. Skin necrosis due to cold agglutinins is very rare? We present a dramatic case of cold agglutinin-induced skin ne~rosis at three different sites of intravenous infusion, which occurred in the setting of hemolysis due primarily to the cold agglutinin. Case report. A 72-year-old white woman developed a hemolytic anemia following an elective lumbar lamineetomy. Thirteen days postoperatively, she developed cutaneous necrosis and secondary ulceration in the right antecubital fossa at the site of an intravenous line that had been used solely for red blood cell and saline infusions. At this time she had a positive direct (IgG and C3) and indirect Coombs' test reaction. The IgG was due to an anti-C red cell antibody that developed following perioperative transfusions. The C3 was believed to be due to the cold agglutinin complement fixation. Six weeks later, as her hemolysis continued despite transfusions of C antigen-negative red blood cells, cold hemagglutinin tests were performed. She was reported to have IgM antibodies to both I
Journal of the American Academy of Dermatology
Fig. 1. Large hemorrhagic bulla with central necrosis present over the right lateral malleolus.
and i in a titer of 1:256 at 4 ~ C. At room temperature she had anti-i antibodies at a titer of 1:32. Cryoglobulin and cryofibrinogen test results were negative. Eight weeks postoperatively, dermatologic consultation was requested when skin necrosis developed again at two different peripheral intravenous infusion sites on two consecutive days. The infusion sites, veins on the lateral aspects of the left and right ankles, had been used solely for blood and saline infusion. The patient was not on coumarin and had been receiving only "minidose" heparin, 5000 U administered subcutaneously twice daily over the abdominal area. On examination, the patient was jaundiced. There was a 10 cm hemorrhagic bulla with a central 1.5 cm area of necrosis on the right lateral aspect of the ankle (Fig. 1) and a 5 cm area of hemorrhage with evidence of early necrosis over the left lateral aspect of the ankle. There was also a 2 • 2-cm ulceration in the right antecubital fossa, with subcutaneous adipose tissue exposed at the base. Both ankle lesions progressed to fullthickness skin necrosis similar to that of the earlier lesion in the right antecubital fossa. Histologic examination of a skin biopsy specimen obtained from the left ankle within 24 hours of the onset of necrosis showed extensive capillary thrombosis with intravascular fibrin deposition. There was no evidence of vasculitis and only minimal inflammation was present (Fig. 2). The diagnosis of cold agglutinin-induced skin necrosis was made.
Volume 19 Number 2, Part 1 August 1988
Fig. 2. Photomicrograph of punch biopsy specimen from the left ankle, showing thrombosis of small dermal capillaries. (Hematoxylin-eosin stain; Xl00.)
Subsequently, strict attention was paid to keeping both the patient and the infused blood warm, and no further skin necrosis occurred. The skin lesionsslowlyhealed, and over the next 6 weeks her hemolysis stopped. Discussion. Cutaneous disease due to cold agglutinins is usually limited to acral cyanosis, but cold urticaria or livedo reticularis may also occur. Although cases of skin necrosis with cold agglutinins have been reported, 2 such an event is very rare, probably because the agglutination is rapidly reversible on warming. Our patient's dramatic presentation is unique; a literature review did not uncover any similar cases. The occurrence of cutaneous necrosis at three different sites of intravenous infusion at different times in the setting of a hemolytic anemia due to cold agglutinins makes a strong case for cold agglutinins as the cause of our patient's skin necrosis. Cold agglutinins are immunoglobulins, most often of the IgM class, which, as their name implies, are able to agglutinate red blood cells at temperatures below normal body temperature. There are two major types of cold agglutinins. Monoclonal cold agglutinins occur with lymphoreticular neoplasia or as an idiopathic disease, while polyclonal cold agglutinins usually occur in the setting of an infection, especially Mycoplasma pneumoniae. Variable degrees of chronic hemolysis and exacerbations with cold exposure may occur with either type. Cold agglutinins usually recognize the Ii antigens on red cell membranes. Normal adult and infant serum may contain very small amounts of IgM anti-I, which will cause agglutination under laboratory conditions at 0-5 ~ These normally appearing antibodies are not clinically relevant. The clinically relevant cold aggluti-
Correspondence 357
nins are capable of binding red cells at temperatures near to body temperature and are present in a much higher titer. Since superficial vessels in the acral areas have temperatures of 28-30 ~ it is in these areas that in vivo binding of cold agglutinins is believed to occur. Sludging in these vessels due to agglutination may result in the clinical findings of acrocyanosis, tivedo reticularis, or Raynaud's phenomenon. These antibodies are also capable of fixing complement and may do so at significantly higher temperatures than those needed to cause agglutination) Completion of the complement cascade results in hemolysis and the clinical syndrome of hemolytic anemia and hemoglobinuria. It is important to distinguish cold agglutinin, cryoglobulin, and cryofibrinogen-induced skin disease. Each of these proteins although distinct, may cause prominent skin manifestations, including acral necrosis. The definitive detection of cold agglutinins is made in the laboratory by the agglutination of saline-suspended red blood cells at low temperatures. The mainstay of therapy of cold agglutinin disease is to keep the patient warmed, above the thermal amplitude of the cold agglutinins. Fortunately, cases not due to underlying lymphoreticular neoplasia are often selflimiting, as was the case in our patient.
Mary Seabury Stone, M.D., Warren W. Piette, M.D., and W. Patrick Davey, M.D., University of Iowa Hospitals and Clinics, Iowa City, IA REFERENCES 1. Paekman CH, Leddy JP. Cryopathic hemolytic syndromes. In: Williams WJ, Beutler E, Erslev AJ, Leehtman MA, eds. Hematology. 3rd ed. New York: McGraw-Hill, 1983:642-7. 2. Barth JH. Infectious mononucleosis(glandular fever) complicated by cold agglutinins, cold urticaria and leg ulceration. Acta Derm Venereol (Stockh) 1981;61:451-2.
Tinea versicolor in immunosuppressed patients To the Editor," Daneshvar and Hashimoto recently reported an unusual presentation of tinea versicolor in an immunosuppressed patient (J AM ACAD DERMA'rOL 1987;17:304-5). We, too, report a patient who presented with a facial rash that proved to be tinea versicolor. Case report. A 53-year-old man came to our clinic with a 6-week history of a red, scaly, pruritic rash on the face. Over the preceding 2 weeks he had noticed extension of the lesions to the upper part of the trunk and the shoulders. Past medical history revealed null cell acute lymphoblastic leukemia diagnosed in June 1985. This had been treated successfully with
Correspondence
5. Brown CF, Gallup DG, Brown VM. Hidraderftis suppurafiva of the anogenital region responsive to isotretinoin: a case report and review of the literature. [abstract]. South Med J 1986;79:9(suppl 2:23). 6. Jones DH, Cunliffe W J, King K. Hidradenitis suppurativa--laek of success with 13-cis-retinoie acid [letter]. Br J Dermatol 1982;107:252. 7. Norris JFB, Cunliffe WJ. Failure of treatment of familial widespread hidradenitis suppurativa with isotretinoin. Clin Exp Dermatol 1986;11:579-83. 8. Stewart WD, Light ML Successful treatment of hidradenitis suppurativa with etretinate. [abstract]. Dermatologica 1984;169:258. 91 Paravieini U, Camenzind M, Gower M, et al. Multiple dose pharmacokinetics of Ro 10-1670, the main metabolate of etretinate (Tigason). In: Saurat J-H, ed. Retinoids: new trends in research and therapy. New York: S Karger, 1985:289-92. 10. Goldstein JA, Socha-Szott A, Thomsen R J, Pochi PE, Shalita AR, Strauss JS. Comparative effect ofisotretinoin and etretinate on acne and sebaceous gland secretion. J AM ACAD DEgMATOL1982;6:760-5. 11. Harms M, Philippe I, Radeff B, et al. Arotinoid Ro 13-6298 and etretin: two new retinoids inferior to isotretinoin in sebum suppression and ache treatment. Acta Derm Venereol (Stoekh) 1986;66:149-54. 12. Bradshaw D, Cashin CH, Kennedy AJ. Further studies on the anti-inflammatory effects of retinoids. In: Saurat JH, ed. Retinoids: new trends in research and therapy. New York: S Karger, 1985:204-18. 13. Elias PM, Williams ML. Retinoid effects on epidermal differentiation. In: Saurat JH, ed. Refinoids: new trends in research and therapy. New York: S Karger, 1985:13858.
Cutaneous necrosis at sites of transfusion: Cold agglutinin disease To the Editor: Cutaneous manifestations associated with cold agglutinins are usually confined to reversible acrocyanosis. Skin necrosis due to cold agglutinins is very rare? We present a dramatic case of cold agglutinin-induced skin ne~rosis at three different sites of intravenous infusion, which occurred in the setting of hemolysis due primarily to the cold agglutinin. Case report. A 72-year-old white woman developed a hemolytic anemia following an elective lumbar lamineetomy. Thirteen days postoperatively, she developed cutaneous necrosis and secondary ulceration in the right antecubital fossa at the site of an intravenous line that had been used solely for red blood cell and saline infusions. At this time she had a positive direct (IgG and C3) and indirect Coombs' test reaction. The IgG was due to an anti-C red cell antibody that developed following perioperative transfusions. The C3 was believed to be due to the cold agglutinin complement fixation. Six weeks later, as her hemolysis continued despite transfusions of C antigen-negative red blood cells, cold hemagglutinin tests were performed. She was reported to have IgM antibodies to both I
Journal of the American Academy of Dermatology
Fig. 1. Large hemorrhagic bulla with central necrosis present over the right lateral malleolus.
and i in a titer of 1:256 at 4 ~ C. At room temperature she had anti-i antibodies at a titer of 1:32. Cryoglobulin and cryofibrinogen test results were negative. Eight weeks postoperatively, dermatologic consultation was requested when skin necrosis developed again at two different peripheral intravenous infusion sites on two consecutive days. The infusion sites, veins on the lateral aspects of the left and right ankles, had been used solely for blood and saline infusion. The patient was not on coumarin and had been receiving only "minidose" heparin, 5000 U administered subcutaneously twice daily over the abdominal area. On examination, the patient was jaundiced. There was a 10 cm hemorrhagic bulla with a central 1.5 cm area of necrosis on the right lateral aspect of the ankle (Fig. 1) and a 5 cm area of hemorrhage with evidence of early necrosis over the left lateral aspect of the ankle. There was also a 2 • 2-cm ulceration in the right antecubital fossa, with subcutaneous adipose tissue exposed at the base. Both ankle lesions progressed to fullthickness skin necrosis similar to that of the earlier lesion in the right antecubital fossa. Histologic examination of a skin biopsy specimen obtained from the left ankle within 24 hours of the onset of necrosis showed extensive capillary thrombosis with intravascular fibrin deposition. There was no evidence of vasculitis and only minimal inflammation was present (Fig. 2). The diagnosis of cold agglutinin-induced skin necrosis was made.
Volume 19 Number 2, Part 1 August 1988
Fig. 2. Photomicrograph of punch biopsy specimen from the left ankle, showing thrombosis of small dermal capillaries. (Hematoxylin-eosin stain; Xl00.)
Subsequently, strict attention was paid to keeping both the patient and the infused blood warm, and no further skin necrosis occurred. The skin lesionsslowlyhealed, and over the next 6 weeks her hemolysis stopped. Discussion. Cutaneous disease due to cold agglutinins is usually limited to acral cyanosis, but cold urticaria or livedo reticularis may also occur. Although cases of skin necrosis with cold agglutinins have been reported, 2 such an event is very rare, probably because the agglutination is rapidly reversible on warming. Our patient's dramatic presentation is unique; a literature review did not uncover any similar cases. The occurrence of cutaneous necrosis at three different sites of intravenous infusion at different times in the setting of a hemolytic anemia due to cold agglutinins makes a strong case for cold agglutinins as the cause of our patient's skin necrosis. Cold agglutinins are immunoglobulins, most often of the IgM class, which, as their name implies, are able to agglutinate red blood cells at temperatures below normal body temperature. There are two major types of cold agglutinins. Monoclonal cold agglutinins occur with lymphoreticular neoplasia or as an idiopathic disease, while polyclonal cold agglutinins usually occur in the setting of an infection, especially Mycoplasma pneumoniae. Variable degrees of chronic hemolysis and exacerbations with cold exposure may occur with either type. Cold agglutinins usually recognize the Ii antigens on red cell membranes. Normal adult and infant serum may contain very small amounts of IgM anti-I, which will cause agglutination under laboratory conditions at 0-5 ~ These normally appearing antibodies are not clinically relevant. The clinically relevant cold aggluti-
Correspondence 357
nins are capable of binding red cells at temperatures near to body temperature and are present in a much higher titer. Since superficial vessels in the acral areas have temperatures of 28-30 ~ it is in these areas that in vivo binding of cold agglutinins is believed to occur. Sludging in these vessels due to agglutination may result in the clinical findings of acrocyanosis, tivedo reticularis, or Raynaud's phenomenon. These antibodies are also capable of fixing complement and may do so at significantly higher temperatures than those needed to cause agglutination) Completion of the complement cascade results in hemolysis and the clinical syndrome of hemolytic anemia and hemoglobinuria. It is important to distinguish cold agglutinin, cryoglobulin, and cryofibrinogen-induced skin disease. Each of these proteins although distinct, may cause prominent skin manifestations, including acral necrosis. The definitive detection of cold agglutinins is made in the laboratory by the agglutination of saline-suspended red blood cells at low temperatures. The mainstay of therapy of cold agglutinin disease is to keep the patient warmed, above the thermal amplitude of the cold agglutinins. Fortunately, cases not due to underlying lymphoreticular neoplasia are often selflimiting, as was the case in our patient.
Mary Seabury Stone, M.D., Warren W. Piette, M.D., and W. Patrick Davey, M.D., University of Iowa Hospitals and Clinics, Iowa City, IA REFERENCES 1. Paekman CH, Leddy JP. Cryopathic hemolytic syndromes. In: Williams WJ, Beutler E, Erslev AJ, Leehtman MA, eds. Hematology. 3rd ed. New York: McGraw-Hill, 1983:642-7. 2. Barth JH. Infectious mononucleosis(glandular fever) complicated by cold agglutinins, cold urticaria and leg ulceration. Acta Derm Venereol (Stockh) 1981;61:451-2.
Tinea versicolor in immunosuppressed patients To the Editor," Daneshvar and Hashimoto recently reported an unusual presentation of tinea versicolor in an immunosuppressed patient (J AM ACAD DERMA'rOL 1987;17:304-5). We, too, report a patient who presented with a facial rash that proved to be tinea versicolor. Case report. A 53-year-old man came to our clinic with a 6-week history of a red, scaly, pruritic rash on the face. Over the preceding 2 weeks he had noticed extension of the lesions to the upper part of the trunk and the shoulders. Past medical history revealed null cell acute lymphoblastic leukemia diagnosed in June 1985. This had been treated successfully with