- Email: [email protected]
Herpes simplex mimicking leukemia cutis
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Herpes simplex mimicking leukemia cutis Mark H. Hassel, MD, and Jack L. Lesher, Jr., MD Augusta, Georgia We present a patient with chronic lymphocytic leukemia who developed a painful penile ulcer that was initially diagnosed as leukemia cutis, as evidenced by an atypical leukemic infiltrate on biopsy. A Tzanck preparation was positive for multinucleated giant cells, and the diagnosis of herpes genitalis was confirmed by viral culture. In patients with hematologic malignancies, herpes simplex virus must be included in the differential diagnosis of ulcerative lesions. The histopathologic findings of inflammatory dermatoses in these patients may include an atypical infiltrate, because of the predominance of atypical inflammatory cells in the peripheral circulation. (J AM ACAD DERMATOL 1989;21:367-71.) Immunosuppressed patients with hematologic malignancies are especially susceptible to infection? Infection is the leading cause of death in patients with acute leukemia) and herpes simplex virus is among the most common mucocutaneous infections in immunosuppressed patients) Herpes simplex virus infections are particularly common in the leukemias and may cause an unusually severe progressive or chronic localized ulcer (herpes phagedena) in patients with leukemia. 1'.6 These patients are not typically acutely ill. Cutaneous manifestations of leukemia and lymphoma may be specific or nonspecific. Specific cutaneous lesions are often plum-colored papules or nodules that contain the same histologie elements that characterize the lymphoproliferative disorder. 7 Nonspecific lesions are much more common than specific lesions and include chronic ulcers of herpes simplex, herpes zoster, purpura, pruritus with excoriations, prurigo-like papules, bullous pemphigoid, ichthyosis, ulcerative gingivitis, pallor of anemia, vasculitis, cutis verticis gyrata, exfoliative erythroderrna, erythema multiforme, bullous pyoderm a gangrenosum, urticaria, hyperpigmentation, Sweet's syndrome, and morbilliform eruptions and lesions of bacterial, fungal, and other viral infections, s-m Leukemid is a somewhat confusing term that applies to lesions clinically resembling nonspecific cutaneous lesions but histologically having
From the Department of Dermatology, Medical College of Georgia. Reprint requests: Mark H. Hassel, MD, Department of Dermatology, Medical College of Georgia, Augusta, GA 30912.
characteristics suggestive of specific or true cutaneous inflammation by leukemic cellsJ ~ In this report a patient with chronic lymphocytic leukemia who had an ulcerated penile lesion initially had the diagnosis of a specific cutaneous lesion of leukemia (ulcerating leukemia cutis) after routine histopathologic evaluation showed an atypical lymphocytic infiltrate. Subsequent studies, however, indicated that the lesion was of herpetic origin. The inguinal nodes also were shown to be involved with the herpetic process. The cutaneous lesions showed marked improvement with oral and topical acyclovir therapy. CASE REPORT
A 55-year-old black man was referred to the urology service of the Medical College of Georgia in September 1986 with a history of an ulcerative penile lesion for 3 weeks. He complained of a 20-pound weight loss during the past 6 months. His local physician had recently prescribed oral tetracycline, 500 mg four times daily, and 0.1% gentamiein sulfate ointment, to be applied topically to the lesion twice daily. Medical history of the patient was significant for a 5-year history of lymphatic leukemia, which his local physician had treated with ehlorambucil. There was no prior surgical history nor a history of sexually transmitted diseases, hepatitis, sickle cell disease, or diabetes mellitus. Physical examination revealed a thin black man in no acute distress appearing somewhat older than his stated age. Vital signs were normal. Significant findings included anterior and posterior cervical adenopathy and large, fixed inguinal adenopathy more pronounced on the left side. A tender, malodorous ulcer was found on 367
368
Hassel and Lesher
Journal of the American Academy of Dermatology
Fig. 1. Appearance of penile lesion when patient came to dermatology service. Note atypical appearance of this ulcer. Fig. 2. Photomicrograph of atypical inflammatory infiltrate in penile biopsy specimen. Inflammatory ceils have atypical-appearing nuclei with prominent nucleoli. (Hematoxylineosin stain; •
the glans and distal shaft of the penis (Fig. 1). There were no other skin or mucous membrane lesions. Results of the following laboratory studies (obtained on the patient's admission by the urology service) were within normal limits: electrocardiogram, anteroposterior and lateral chest films, prothrombin time, partial thromboplastin time, and platelet count. The leukocyte count was 23.3 L/mm 3 with a differential of 18% segmented neutrophils, 68% lymphocytes, and 14% atypical lymphocytes. The results of routine chemistries were normal except for an increased alkaline phosphatase level, 119 mU/ml (normal 25 to 100 mU/ml) and a decreased level of serum iron, 22 ~tg/dl (normal 50 to 150 Fzg/dl). A dark-field examination of the lesion showed negative results; however, results of tests for rapid plasma reagin and microhemagglutination assay-Treponema pallidum were positive on two occasions. Titers for both human immunodeficiency virus and lymphogranuloma venereum showed negative findings. A biopsy specimen of the penile lesion was interpreted by a general pathologist to be leukemia cutis. The cells in the infiltrate did not have the appearance of chronic lymphocytic leukemia and were believed to represent a more malignant transformation (Fig. 2). Stains for
fungi, bacteria, Donovan bodies, and spirochetes (Warthin-Starry) were all negative. Immunoperoxidase staining for kappa and lambda light chains was negative. One week after admission, the dermatology service was consulted. A Tzanck preparation of the ulcerative lesion yielded many characteristic giant cells with viral inclusion bodies (Fig. 3). Results of a direct fluorescence antibody test was negative for herpes; however, herpes simplex virus was identified from viral cultures of the lesion. Oral acyclovir (200 mg five times daily) and topical 5% acyclovir ointment (five times daily) therapies were started, and the patient showed marked improvement in a relatively short period (from Sept. 16, 1986, to Oct. 3, 1986; see Figs. I and 4). Two bone marrow specimens obtained earlier in the course of the patient's illness (one from April 1984, one from January 1985) were reviewed by our hematology service; diagnosis of chronic lymphocytic leukemia was confirmed. An inguinal node biopsy specimen was obtained 1 month after the patient came to the dermatology service (i.e., on Oct. 20, 1986). Flow cytometry phenotypic analysis of this tissue was consistent with a B cell lymphoproliferative disorder. Review of the biopsy
Volume 21 Number 2, Part 2 August 1989
Herpes simplex mimicking leukemia eutis 369
+
,
-
9
~%:+ .~
@
+2
++
o,
9
i L si i+i,
r 84 ::+i
+
Fig. 3. Actual Tzanck preparation from our patient. Characteristic viral inclusion bodies are present. '(Giemsa stain; Xl60.) Fig. 4. Appearance of penile lesion 17 days after oral and topical acyclovir therapy. Clinical improvement is readily apparent, with mainly postinflammatory hypopigmentation remaining. Fig. 5. Photomicrograph of penile biopsy specimen. Immunoperoxidase staining specific for herpes simplex virus clearly demonstrates involved cells by staining them red. (Immunoperoxidase stain; x40.)
material indicated a lymphoproliferative disorder most consistent with an intermediate lymphocytic lymphoma by the international classification. Tissue sections stained with special stains, including acid-fast, Gomori methenarnine silver, Gridley, McCallum-Goodpasture, and periodic acid-Schiff, were negative for organisms.
Immunoperoxidase staining of tissue sections for kappa light chains showed strongly positive findings, but results of similar staining for lambda light chains was negative. Immunoperoxidase staining specific for herpes simplex virus was performed subsequently on both penile
370
Journal of the American Academy of Dermatology
Hassel and Lesher
and lymph node tissues. As expected, the penile biopsy specimen was positive (Fig. 5); interestingly, the lymph node biopsy specimen also was strongly positive. Recuts of the penile biopsy specimen showed multinucleated giant cells plainly visible in the preparation stained with hematoxylin and eosin at the areas positive for herpes simplex virus by immunoperoxidase stain. Although the patient's cutaneous lesions improved with therapy, his medical condition worsened. Two months after being discharged he died from complications related to his systemic illness. An autopsy was not performed. DISCUSSION Atypical herpes simplex virus infections in patients with hematologic malignancies have been well documented) ,~2-16 Nonspecific dermatologic manifestations of hematologic malignancies are far more common than specific lesions. In chronic lymphocytic leukemia, specific lesions occur in 8.3% of patients whereas nonspecific lesions occur in 45% of patients, s In patients with chronic lymphocytic leukemia, nonspecific lesions of leukemia are encountered five times as often as specific lesions. In our case an atypical infiltrate was interpreted initially as sufficient evidence for a specific leukemic lesion. O u r initial impressions were biased toward a more malignant transformation because the infiltrate did not have the appearance of typical cells of chronic lymphocytic leukemia. In a histopathologic study, Buechner et al. 17 examined 42 cases of leukemia curls and found that leukemia curls lacks a consistent histologic pattern, necessitating a reliance on morphologic and histochemical studies of smears of peripheral blood or bone marrow for a final typing of a leukemia. ~7 Therefore skin biopsies alone do not provide enough information to characterize accurately a type of leukemia. In chronic lymphocytic leukemia, leukemia curls m a y be manifested as nodules, infiltrations or plaques, ulcerative lesions, or exfoliative erythroderma." On rare occasions ulcerative leukemic lesions have been reported on the genitalia." Infiltration by leukemic cells m a y occur in nonspectfie lesions of leukemia. These infiltrates have been reported in sites of intramuscular injections, scars from recent surgery, scars from herpes zoster, herpes zoster lesions, sites of recent trauma, burns, and herpes simplex lesions. ",~a'22 To make the sole diagnosis of leukemia curls, an infectious
cause must be excluded even if histologic study shows an atypical leukemic infiltrate. A workup, which includes a Tzanck preparation and herpes cultures, as well as biopsies and cultures for other infectious causative agents, should be done on all ulcerative lesions in patients with hematologic malignancies. Herpes simplex lymphadenitis can mimic malignant lymphoid proliferations. Audouin et al. ~3 reported a case of herpes simplex virus lymphadenitis that simulated tumor relapse in a patient with Hodgkin's disease in remission. Both suppurative necrosis and severe hisrlocytosis within the node are features suggesting a viral cause. Although a thorough search for typical intranuclear inclusions should be conducted, immunochemistry or electron microscopy are the most important means to demonstrate definitively a viral cause for lymphadenitis. 2s In our case, immunoperoxidase staining specific for herpes simplex virus demonstrated viral particles within the areas of necrosis in the node. These findings were accompanied by an atypical lymphocytic infiltrate showing features of a lymphocytic leukemia. W e conclude that patients with hematologic malignancies and ulcerative skin lesions must be examined completely for infectious causes before labeling a cutaneous lesion as leukemia curls even if examination of the biopsy specimen shows a leukemic infiltrate. Furthermore, when adenopathy is observed in an immunocompromised patient with culture-proved herpes simplex virus cutaneous lesions, herpes simplex virus lymphadenitis should be considered.
REFERENCES
1. Muller SA, Herrmarm EC, Winkelmann RK. Herpes simplex infections in hematologic malignancies. Am J Med 1972;52:102-14. 2. Chang H-Y, Rodriquez V, Narboni G, Bodey G, Luna M, Freireich E, Causes of death in adults with acute leukemia. Medicine 1976;55:259-68. 3. Shalev Y, Berrebi A, Green L, et al. Progressivecutaneous herpes simplex infection in acute myeloblasticleukemia. Arch Dermatol 1984;120:922-6. 4. Aston DL, Cohen A, Spindler MA. Herpesvirus hominis infection in patients with myeloproliferativeand lymphoproliferative disorders. Br Med J 1972;4:462-5. 5. Cormia FE, Domonkos AN. Cutaneous reactions to internal malignancy. Med Clin North Am 1965;49:65580. 6. Feldman S, Cox F. Viral infections and haematological malignancies. Clin Haematol 1976;5:311-28. 7. Rosen T. Leukemia and lymphoma: recognizing cutane-
Volume 21 Number 2, Part 2 August 1989
8. 9. 10. 11. 12. 13. 14.
15.
Herpes simplex mimicking leukemia cutis
ous signs of internal malignancies. Geriatrics 1980; 35(12):65-72. Stawiski MA. Skin manifestations of leukemias and lymphomas. Cuffs 1978;21:814-8. Buffer DF, Berger TG, Rodman OG. Leukemia curls mimicking stasis dermatitis. Cuffs 1985;35:47-8. Su WPD, Buechner SA, Li C-Y. Clinicop~tthologie correlations in leukemia cutis. J AM ACAD DERMATOL 1984;11:121-8. Bluefarb SM. Leukemia eutis. Springfield, IlL: Charles C Thomas, 1960:55-78. Vonderheid EC, Milstein HJ, Thompson KID, Wu BC. Chronic herpes simplex infection in cutaneous T-cell lymphomas. Arch Dermatol 1980;116:1018-22. Goldgeier MH, Cohen SR, Braverman IM, Stenn KS. An unusual and fatal case of disseminated cutaneous herpes simplex. J AM Acho DERMATOL1981;4:176-80. Lam MT, Pazin GJ, Armstrong JA, Ho M. Herpes simplex infection in acute myelogenous leukemia and other hematologic malignancies. Cancer 1981;48:216871. Bean SF, Fusaro RM. Atypical cutaneous herpes simplex infection associated with acute myelogenous leukemia. Acta Derm Venereol (Stockh) 1969;49:94-6.
I
II I
16. Leming PD, Martin SE, Zwelling LA. Atypical herpes simplex (HSV) infection in a patient with Hodgkin's disease. Cancer 1984;54:3043-7. 17. Buechner SA, Li C-Y, Su WPD. Leukemia cutis: a histopathologie study of 42 cases. Am J Dermatopathol 1985;7:109-19. 18. Braverman IM. Skin signs of systemic disease. 2nd ed. Philadelphia: WB Saunders, 1981:180-I. 19. Cleland JB. Leukaemic infiltrations. Br Med J 1935; 2:1191-4. 20. Anhalt AW, Forsey RR. Herpes zoster, leukaemia curls and leukaemic infiltration of the lesions of herpes zoster. Can Med Assoc J 1956;75:750-1. 21. Barton RL, O'Leary PA. Herpes zoster generalisatus associated with chronic lymphatic leukemia. Arch Dermatol Syph 1945;51:263-5. 22. Caffin CH. Leukaemic infiltration of the site of herpes zoster. Br Med J 1946;1:801. 23. Audouin J, Tourneau AL, Aubert JP, Diebold J. Herpes simplex virus lymphadenitis mimicking tumoral relapse in a patient with Hodgkin's disease in remission, Virchows Arch 1985;408:313-21.
IIII
Reactive perforating collagenosis in a setting of double disaster: Acquired immunodeficiency syndrome and end-stage renal disease David E. Bank, MD, Philip R. Cohen, MD, and Steven R. Kohn, MD New York, New York We report reactive perforatingcollagenosisin an intravenousheroin abuser with acquired immunodeficiency syndrome and end-stage renal disease. The literature on perforating disorders in patients with acquired immunodeficiency syndrome and the pathogenesis of reactive perforating coUagenosis in this setting is reviewed. (J AM ACAO DERMATOL 1989;21:371-4.)
The recent plethora of publications on cutaneous manifestations of acquired immunodeficiency syndrome (AIDS) has included not only viral, fungal, bacterial, protozoan, and arthropod pathogens,TM but also hypersensitivity syndromes, benign hyperproliferative conditions, benign vascular conditions, malignant neoplasms, and miscellaneous disor-
ders: ,s We report a case of reactive perforating collagenosis developing in a patient with AIDS and end-stage renal disease. To our knowledge, reactive perforating collagenosis has never been described in association with AIDS or in association with end-stage renal disease as a result of either heroin nephropathy7 or human immunodeficiency virus (HIV) nephropathy:
From the Department of Dermatology, College of Physicians and Surgeons of Columbia University. Reprint requests: David E. Bank, MD, Departmentof Dermatology, College of Physicians and Surgeons of Columbia University, 630 W. 168th St., New York, NY 10032.
CASE R E P O R T A 38-year-old black man with a history of intravenous drug abuse and a diagnosis of AIDS came to Columbia-Presbyterian Medical Center in April 1986
371
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Herpes simplex mimicking leukemia cutis Mark H. Hassel, MD, and Jack L. Lesher, Jr., MD Augusta, Georgia We present a patient with chronic lymphocytic leukemia who developed a painful penile ulcer that was initially diagnosed as leukemia cutis, as evidenced by an atypical leukemic infiltrate on biopsy. A Tzanck preparation was positive for multinucleated giant cells, and the diagnosis of herpes genitalis was confirmed by viral culture. In patients with hematologic malignancies, herpes simplex virus must be included in the differential diagnosis of ulcerative lesions. The histopathologic findings of inflammatory dermatoses in these patients may include an atypical infiltrate, because of the predominance of atypical inflammatory cells in the peripheral circulation. (J AM ACAD DERMATOL 1989;21:367-71.) Immunosuppressed patients with hematologic malignancies are especially susceptible to infection? Infection is the leading cause of death in patients with acute leukemia) and herpes simplex virus is among the most common mucocutaneous infections in immunosuppressed patients) Herpes simplex virus infections are particularly common in the leukemias and may cause an unusually severe progressive or chronic localized ulcer (herpes phagedena) in patients with leukemia. 1'.6 These patients are not typically acutely ill. Cutaneous manifestations of leukemia and lymphoma may be specific or nonspecific. Specific cutaneous lesions are often plum-colored papules or nodules that contain the same histologie elements that characterize the lymphoproliferative disorder. 7 Nonspecific lesions are much more common than specific lesions and include chronic ulcers of herpes simplex, herpes zoster, purpura, pruritus with excoriations, prurigo-like papules, bullous pemphigoid, ichthyosis, ulcerative gingivitis, pallor of anemia, vasculitis, cutis verticis gyrata, exfoliative erythroderrna, erythema multiforme, bullous pyoderm a gangrenosum, urticaria, hyperpigmentation, Sweet's syndrome, and morbilliform eruptions and lesions of bacterial, fungal, and other viral infections, s-m Leukemid is a somewhat confusing term that applies to lesions clinically resembling nonspecific cutaneous lesions but histologically having
From the Department of Dermatology, Medical College of Georgia. Reprint requests: Mark H. Hassel, MD, Department of Dermatology, Medical College of Georgia, Augusta, GA 30912.
characteristics suggestive of specific or true cutaneous inflammation by leukemic cellsJ ~ In this report a patient with chronic lymphocytic leukemia who had an ulcerated penile lesion initially had the diagnosis of a specific cutaneous lesion of leukemia (ulcerating leukemia cutis) after routine histopathologic evaluation showed an atypical lymphocytic infiltrate. Subsequent studies, however, indicated that the lesion was of herpetic origin. The inguinal nodes also were shown to be involved with the herpetic process. The cutaneous lesions showed marked improvement with oral and topical acyclovir therapy. CASE REPORT
A 55-year-old black man was referred to the urology service of the Medical College of Georgia in September 1986 with a history of an ulcerative penile lesion for 3 weeks. He complained of a 20-pound weight loss during the past 6 months. His local physician had recently prescribed oral tetracycline, 500 mg four times daily, and 0.1% gentamiein sulfate ointment, to be applied topically to the lesion twice daily. Medical history of the patient was significant for a 5-year history of lymphatic leukemia, which his local physician had treated with ehlorambucil. There was no prior surgical history nor a history of sexually transmitted diseases, hepatitis, sickle cell disease, or diabetes mellitus. Physical examination revealed a thin black man in no acute distress appearing somewhat older than his stated age. Vital signs were normal. Significant findings included anterior and posterior cervical adenopathy and large, fixed inguinal adenopathy more pronounced on the left side. A tender, malodorous ulcer was found on 367
368
Hassel and Lesher
Journal of the American Academy of Dermatology
Fig. 1. Appearance of penile lesion when patient came to dermatology service. Note atypical appearance of this ulcer. Fig. 2. Photomicrograph of atypical inflammatory infiltrate in penile biopsy specimen. Inflammatory ceils have atypical-appearing nuclei with prominent nucleoli. (Hematoxylineosin stain; •
the glans and distal shaft of the penis (Fig. 1). There were no other skin or mucous membrane lesions. Results of the following laboratory studies (obtained on the patient's admission by the urology service) were within normal limits: electrocardiogram, anteroposterior and lateral chest films, prothrombin time, partial thromboplastin time, and platelet count. The leukocyte count was 23.3 L/mm 3 with a differential of 18% segmented neutrophils, 68% lymphocytes, and 14% atypical lymphocytes. The results of routine chemistries were normal except for an increased alkaline phosphatase level, 119 mU/ml (normal 25 to 100 mU/ml) and a decreased level of serum iron, 22 ~tg/dl (normal 50 to 150 Fzg/dl). A dark-field examination of the lesion showed negative results; however, results of tests for rapid plasma reagin and microhemagglutination assay-Treponema pallidum were positive on two occasions. Titers for both human immunodeficiency virus and lymphogranuloma venereum showed negative findings. A biopsy specimen of the penile lesion was interpreted by a general pathologist to be leukemia cutis. The cells in the infiltrate did not have the appearance of chronic lymphocytic leukemia and were believed to represent a more malignant transformation (Fig. 2). Stains for
fungi, bacteria, Donovan bodies, and spirochetes (Warthin-Starry) were all negative. Immunoperoxidase staining for kappa and lambda light chains was negative. One week after admission, the dermatology service was consulted. A Tzanck preparation of the ulcerative lesion yielded many characteristic giant cells with viral inclusion bodies (Fig. 3). Results of a direct fluorescence antibody test was negative for herpes; however, herpes simplex virus was identified from viral cultures of the lesion. Oral acyclovir (200 mg five times daily) and topical 5% acyclovir ointment (five times daily) therapies were started, and the patient showed marked improvement in a relatively short period (from Sept. 16, 1986, to Oct. 3, 1986; see Figs. I and 4). Two bone marrow specimens obtained earlier in the course of the patient's illness (one from April 1984, one from January 1985) were reviewed by our hematology service; diagnosis of chronic lymphocytic leukemia was confirmed. An inguinal node biopsy specimen was obtained 1 month after the patient came to the dermatology service (i.e., on Oct. 20, 1986). Flow cytometry phenotypic analysis of this tissue was consistent with a B cell lymphoproliferative disorder. Review of the biopsy
Volume 21 Number 2, Part 2 August 1989
Herpes simplex mimicking leukemia eutis 369
+
,
-
9
~%:+ .~
@
+2
++
o,
9
i L si i+i,
r 84 ::+i
+
Fig. 3. Actual Tzanck preparation from our patient. Characteristic viral inclusion bodies are present. '(Giemsa stain; Xl60.) Fig. 4. Appearance of penile lesion 17 days after oral and topical acyclovir therapy. Clinical improvement is readily apparent, with mainly postinflammatory hypopigmentation remaining. Fig. 5. Photomicrograph of penile biopsy specimen. Immunoperoxidase staining specific for herpes simplex virus clearly demonstrates involved cells by staining them red. (Immunoperoxidase stain; x40.)
material indicated a lymphoproliferative disorder most consistent with an intermediate lymphocytic lymphoma by the international classification. Tissue sections stained with special stains, including acid-fast, Gomori methenarnine silver, Gridley, McCallum-Goodpasture, and periodic acid-Schiff, were negative for organisms.
Immunoperoxidase staining of tissue sections for kappa light chains showed strongly positive findings, but results of similar staining for lambda light chains was negative. Immunoperoxidase staining specific for herpes simplex virus was performed subsequently on both penile
370
Journal of the American Academy of Dermatology
Hassel and Lesher
and lymph node tissues. As expected, the penile biopsy specimen was positive (Fig. 5); interestingly, the lymph node biopsy specimen also was strongly positive. Recuts of the penile biopsy specimen showed multinucleated giant cells plainly visible in the preparation stained with hematoxylin and eosin at the areas positive for herpes simplex virus by immunoperoxidase stain. Although the patient's cutaneous lesions improved with therapy, his medical condition worsened. Two months after being discharged he died from complications related to his systemic illness. An autopsy was not performed. DISCUSSION Atypical herpes simplex virus infections in patients with hematologic malignancies have been well documented) ,~2-16 Nonspecific dermatologic manifestations of hematologic malignancies are far more common than specific lesions. In chronic lymphocytic leukemia, specific lesions occur in 8.3% of patients whereas nonspecific lesions occur in 45% of patients, s In patients with chronic lymphocytic leukemia, nonspecific lesions of leukemia are encountered five times as often as specific lesions. In our case an atypical infiltrate was interpreted initially as sufficient evidence for a specific leukemic lesion. O u r initial impressions were biased toward a more malignant transformation because the infiltrate did not have the appearance of typical cells of chronic lymphocytic leukemia. In a histopathologic study, Buechner et al. 17 examined 42 cases of leukemia curls and found that leukemia curls lacks a consistent histologic pattern, necessitating a reliance on morphologic and histochemical studies of smears of peripheral blood or bone marrow for a final typing of a leukemia. ~7 Therefore skin biopsies alone do not provide enough information to characterize accurately a type of leukemia. In chronic lymphocytic leukemia, leukemia curls m a y be manifested as nodules, infiltrations or plaques, ulcerative lesions, or exfoliative erythroderma." On rare occasions ulcerative leukemic lesions have been reported on the genitalia." Infiltration by leukemic cells m a y occur in nonspectfie lesions of leukemia. These infiltrates have been reported in sites of intramuscular injections, scars from recent surgery, scars from herpes zoster, herpes zoster lesions, sites of recent trauma, burns, and herpes simplex lesions. ",~a'22 To make the sole diagnosis of leukemia curls, an infectious
cause must be excluded even if histologic study shows an atypical leukemic infiltrate. A workup, which includes a Tzanck preparation and herpes cultures, as well as biopsies and cultures for other infectious causative agents, should be done on all ulcerative lesions in patients with hematologic malignancies. Herpes simplex lymphadenitis can mimic malignant lymphoid proliferations. Audouin et al. ~3 reported a case of herpes simplex virus lymphadenitis that simulated tumor relapse in a patient with Hodgkin's disease in remission. Both suppurative necrosis and severe hisrlocytosis within the node are features suggesting a viral cause. Although a thorough search for typical intranuclear inclusions should be conducted, immunochemistry or electron microscopy are the most important means to demonstrate definitively a viral cause for lymphadenitis. 2s In our case, immunoperoxidase staining specific for herpes simplex virus demonstrated viral particles within the areas of necrosis in the node. These findings were accompanied by an atypical lymphocytic infiltrate showing features of a lymphocytic leukemia. W e conclude that patients with hematologic malignancies and ulcerative skin lesions must be examined completely for infectious causes before labeling a cutaneous lesion as leukemia curls even if examination of the biopsy specimen shows a leukemic infiltrate. Furthermore, when adenopathy is observed in an immunocompromised patient with culture-proved herpes simplex virus cutaneous lesions, herpes simplex virus lymphadenitis should be considered.
REFERENCES
1. Muller SA, Herrmarm EC, Winkelmann RK. Herpes simplex infections in hematologic malignancies. Am J Med 1972;52:102-14. 2. Chang H-Y, Rodriquez V, Narboni G, Bodey G, Luna M, Freireich E, Causes of death in adults with acute leukemia. Medicine 1976;55:259-68. 3. Shalev Y, Berrebi A, Green L, et al. Progressivecutaneous herpes simplex infection in acute myeloblasticleukemia. Arch Dermatol 1984;120:922-6. 4. Aston DL, Cohen A, Spindler MA. Herpesvirus hominis infection in patients with myeloproliferativeand lymphoproliferative disorders. Br Med J 1972;4:462-5. 5. Cormia FE, Domonkos AN. Cutaneous reactions to internal malignancy. Med Clin North Am 1965;49:65580. 6. Feldman S, Cox F. Viral infections and haematological malignancies. Clin Haematol 1976;5:311-28. 7. Rosen T. Leukemia and lymphoma: recognizing cutane-
Volume 21 Number 2, Part 2 August 1989
8. 9. 10. 11. 12. 13. 14.
15.
Herpes simplex mimicking leukemia cutis
ous signs of internal malignancies. Geriatrics 1980; 35(12):65-72. Stawiski MA. Skin manifestations of leukemias and lymphomas. Cuffs 1978;21:814-8. Buffer DF, Berger TG, Rodman OG. Leukemia curls mimicking stasis dermatitis. Cuffs 1985;35:47-8. Su WPD, Buechner SA, Li C-Y. Clinicop~tthologie correlations in leukemia cutis. J AM ACAD DERMATOL 1984;11:121-8. Bluefarb SM. Leukemia eutis. Springfield, IlL: Charles C Thomas, 1960:55-78. Vonderheid EC, Milstein HJ, Thompson KID, Wu BC. Chronic herpes simplex infection in cutaneous T-cell lymphomas. Arch Dermatol 1980;116:1018-22. Goldgeier MH, Cohen SR, Braverman IM, Stenn KS. An unusual and fatal case of disseminated cutaneous herpes simplex. J AM Acho DERMATOL1981;4:176-80. Lam MT, Pazin GJ, Armstrong JA, Ho M. Herpes simplex infection in acute myelogenous leukemia and other hematologic malignancies. Cancer 1981;48:216871. Bean SF, Fusaro RM. Atypical cutaneous herpes simplex infection associated with acute myelogenous leukemia. Acta Derm Venereol (Stockh) 1969;49:94-6.
I
II I
16. Leming PD, Martin SE, Zwelling LA. Atypical herpes simplex (HSV) infection in a patient with Hodgkin's disease. Cancer 1984;54:3043-7. 17. Buechner SA, Li C-Y, Su WPD. Leukemia cutis: a histopathologie study of 42 cases. Am J Dermatopathol 1985;7:109-19. 18. Braverman IM. Skin signs of systemic disease. 2nd ed. Philadelphia: WB Saunders, 1981:180-I. 19. Cleland JB. Leukaemic infiltrations. Br Med J 1935; 2:1191-4. 20. Anhalt AW, Forsey RR. Herpes zoster, leukaemia curls and leukaemic infiltration of the lesions of herpes zoster. Can Med Assoc J 1956;75:750-1. 21. Barton RL, O'Leary PA. Herpes zoster generalisatus associated with chronic lymphatic leukemia. Arch Dermatol Syph 1945;51:263-5. 22. Caffin CH. Leukaemic infiltration of the site of herpes zoster. Br Med J 1946;1:801. 23. Audouin J, Tourneau AL, Aubert JP, Diebold J. Herpes simplex virus lymphadenitis mimicking tumoral relapse in a patient with Hodgkin's disease in remission, Virchows Arch 1985;408:313-21.
IIII
Reactive perforating collagenosis in a setting of double disaster: Acquired immunodeficiency syndrome and end-stage renal disease David E. Bank, MD, Philip R. Cohen, MD, and Steven R. Kohn, MD New York, New York We report reactive perforatingcollagenosisin an intravenousheroin abuser with acquired immunodeficiency syndrome and end-stage renal disease. The literature on perforating disorders in patients with acquired immunodeficiency syndrome and the pathogenesis of reactive perforating coUagenosis in this setting is reviewed. (J AM ACAO DERMATOL 1989;21:371-4.)
The recent plethora of publications on cutaneous manifestations of acquired immunodeficiency syndrome (AIDS) has included not only viral, fungal, bacterial, protozoan, and arthropod pathogens,TM but also hypersensitivity syndromes, benign hyperproliferative conditions, benign vascular conditions, malignant neoplasms, and miscellaneous disor-
ders: ,s We report a case of reactive perforating collagenosis developing in a patient with AIDS and end-stage renal disease. To our knowledge, reactive perforating collagenosis has never been described in association with AIDS or in association with end-stage renal disease as a result of either heroin nephropathy7 or human immunodeficiency virus (HIV) nephropathy:
From the Department of Dermatology, College of Physicians and Surgeons of Columbia University. Reprint requests: David E. Bank, MD, Departmentof Dermatology, College of Physicians and Surgeons of Columbia University, 630 W. 168th St., New York, NY 10032.
CASE R E P O R T A 38-year-old black man with a history of intravenous drug abuse and a diagnosis of AIDS came to Columbia-Presbyterian Medical Center in April 1986
371