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Pyoderma gangrenosum in pediatric acquired immunodeficiency syndrome
Pyoderma gangrenosum in pediatric acquired immunodeficiency syndrome Amy S. Paller, MD, Eleanor E. Sahn, MD, Paul D. Garen, MD, Richard L. Dobson, MD, and Ellen Gould Chadwick, MD From the Departments of Pediatrics and Dermatology, The Children's Memorial Hospital of Northwestern University Medical School, Chicago, Illinois, and the Departments of Pediatrics, Dermatology, and Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston
We describe two children with human immunodeficiency virus infection in whom pyoderma gangrenosum developed. Although pyoderma gangrenosum most commonly occurs in children with inflammatory bowel disease, it has also been described in patients with a variety of immunodeficiencies. In such patients a vigorous search to exclude a treatable infection should be m a d e before the lesions are treated as pyoderma gangrenosum. (J PEDIATR1990;117:63-6)
Although pyoderma g a n g r e n o s u m has been described in patients with a variety of immunodeficiency disorders, it has not been reported in a child with the acquired i m m u n o d e ficiency syndrome. W e have observed two children with P G and h u m a n immunodeficiency virus infection. Because of the unusual manifestations of infectious disorders in patients with A I D S , including atypical ulcerations, it is important to eliminate possible infectious causes before concluding t h a t a patient has PG. CASE R E P O R T S Patient 1. A 5-year-old black boy, born in 1984 after a 28-week gestation, weighed 1121 gm at birth. He had neonatal asphyxia and ventricular hemorrhage and required oxygen and ventilation for the first 3 tA months of life. During this period he had multiple cardiac arrests and a cerebrovascular accident, and received multiple blood transfusions. For the first 3 years of life he was clinically well except for panhypopituitarism diagnosed at 7 months of age. As a resuit, he was severely growth retarded and received hydrocortisone and levothyroxine daily and somatrem twice weekly. At 3V2 years of age the patient was kicked in the left preauricular area. Shortly thereafter an ulcer developed at the site and slowly enlarged. Three months after onset, examination revealed a well-circumscribed ulceration with a purulent base and a slightly rolled border that surrounded the ear. A biopsy specimen of the ulSubmitted for publication Jan. 8, 1990; accepted Feb. 9, 1990. Reprint requests: Amy S. Paller, MD, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614. 9/20/20029
cer border showed absence of epidermis and a mixed inflammatory cell dermal infiltrate with no evidence of vasculitis or granulomas. Special stains for bacteria, fungi, and mycobacteria were negative. The ulcer was treated with compresses and polymyxin B-bacitracin ointment, without improvement. Because of the association of PG and inflammatory bowel disease, x-ray examination of the upper gastrointestinal tract, with small bowel follow-through, was performed; results were normal. After two episodes of bacteremic Streptococcus pneumoniae pneumonia, testing for HIV infection was performed and showed the presence of HIV antibodies by both enzyme-linked immunosorbent assay and Western blot assay.
AIDS CMV H1V HSV PG
Acquired immunodeficiency syndrome Cytomegalovirus Human immunodeficiency virus Herpes simplex virus Pyoderma gangrenosum
The patient was first seen at Children's Memorial Hospital 6 months after the ulcer initially developed. By this time the ulcer had enlarged considerably (Fig. 1). Biopsy material was obtained for culture and yielded no aerobic or anaerobic bacteria, fungi, or mycobacteria. Viral cultures of the base of the lesion were negative for herpes simplex virus and varicella-zoster virus. The patient had a concurrent herpetic infection of the lower lip, which responded well to intravenous administration of acyelovir, and a paronychia of the thumb caused by Candida albicans, which responded to treatment with compresses, topica ! econazole, and systemic ketoconazole. The ulcer was again treated with compresses and polymyxin Bbacitracin ointment, and the area was kept wrapped to avoid dis-
63
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The Journal o f Pediatrics July 1990
Fig. 2. Case 2. Pyoderma gangrenosum of mons pubis. Fig. 4. Case 1. Periauricular PG at site of trauma, unresponsive to local therapy.
ruption by the child. The ulcer began to heal during three hospitalizations for pneumonia but repeatedly enlarged while at home. Eleven months after the initial ulcer developed, the child was readmitted with right periorbital cellulitis and a new purulent ulcer on the right eyelid. Dapsone therapy, 12.5 mg twice daily, was initiated, in addition to compresses and topical antibiotics to both ulcers. Within 1 week the eyelid lesion had fully resolved, leaving only a small scar, and the periauricular ulceration showed significant reepithelialization. Two months after the initiation of dapsone therapy, the periauricular ulcer was virtually healed. The patient died suddenly at 5 years of age, while still taking dapsone, of bacterial pneumonia. Patient 2. In a 9-month-old black girl with an unremarkable medical history, except for thrush at age 6 months, an erythematous papule with a blister developed on the mons pubis. Despite antibiotic therapy, this lesion enlarged and ulcerated. A similar lesion developed on the inferior aspect of the right buttock. When fever developed, the child was admitted to the Medical University of South Carolina for examination. On admission the patient had a temperature of 38.5 ~ C and was at less than the 5th percentile for height and weight. She had two ulcers, measuring 2.5 x 3.0 cm on the mons pubis and 1.5 x 1.5 cm in the right perianal region. The ulcers were surrounded by a bluish purple, overhanging border and by an erythematous, 5.0 mm rim (Fig. 2). The center of the larger ulcer was covered with a dried black eschar. Other significant findings included submandibular and inguinal lymphadenopathy, and the liver was palpable 8 cm below the costal margin at the midclavicular line. Cultures from the ulcers revealed scant growth of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Enterococcus species, consistent with fecal contamination. Because of the failure to thrive, lymphadenopathy, and hepatornegaly, HIV antibody titers were measured and were positive by enzyme-linked im-
munosorbent assay and Western blot analysis. T cell subsets showed a decreased T4/T8 ratio of 0.5, and the patient had panhyperglobutinemia. Subsequently, the patient's mother was also found to have HIV antibody by Western blot analysis. The patient was treated with intravenous nafcillin and gentamicin, but the ulcers continued to enlarge. A biopsy specimen of the ulcer on the mons pubis revealed necrosis of the epidermis and underlying dermis but no evidence of epidermal viral cytopathic changes. In the adjacent subcutaneous tissue and dermis were mixed infiltrates of polymorphonuclear leukocytes, lymphocytes, histiocytes, and plasma cells. No evidence of vasculitis or granulomatous inflammation was present. Stains for bacteria, fungi, and mycobacteria revealed no organisms. Cultures of tissue for HSV and varicella-zoster virus were negative. Wet compresses, topical corticosteroids, mupirocin ointment, zinc oxide paste, and protective padding to prevent further trauma from diapers were applied. The ulcers began to heal, and at the time of the patient's discharge 3 weeks later, both ulcers and the biopsy site had healed almost completely. When the patient was 15V2 months of age, results of a repeated HIV antibody tests remained positive and the T4/T8 ratio had decreased further to 0.2. DISCUSSION P y o d e r m a g a n g r e n o s u m is an u n c o m m o n ulcerative skin condition with a distinctive clinical a p p e a r a n c e . It o f t e n begins as a pustule, bulla, or fluctuant n o d u l e that ruptures, f o r m i n g a rapidly enlarging ulcer with a m u c o p u r u l e n t base. T h e m a r g i n o f the ulcer is violaceous a n d u n d e r m i n e d , a n d b e c o m e s m o r e dusky in color as it ages. Lesions a r e most f r e q u e n t l y found on t h e a n t e r i o r a s p e c t o f the legs b u t also occur on t h e face, trunk, and buttocks. T w e n t y p e r c e n t o f p a t i e n t s have a history o f t r a u m a to t h e involved site ( p a t h e r g y ) , as in our patients. T h e ulcer o f t e n heals with an a t r o p h i c or c r i b r i f o r m scar.
Volume 117 Number 1, Part 1
Only 4% of patients with PG are younger than 15 years of ag e.1 Although idiopathic in 17% of reported cases, PG in children may be associated with a variety of underlying systemic disorders 28 (Table). The most common associations in children are inflammatory bowel disease and arthritis. Pyoderma gangrenosum-like ulcers are a common problem in children with leukocyte adhesion deficiencies,9 but bacterial cultures of lesions yield Staphylococcus aureus and, less commonly, gram-negative organisms. Adults with PG and other primary immunodeficiency disorders, including chronic granulomatous disease 1~ and the hyperimmunoglobulinemia E syndrome, 11 have also been described. Although the cause of PG is unknown, its association with this variety of underlying disorders suggests that it is related to host immunologic defects. 12 It was recently reported in a 23-year-old homosexual man with HIV infection, but the ulcers developed 6 years before the antibody testing was performed and the patient had no signs or symptoms of AIDS or AIDS-related complex at the time of antibody testing.13 The immune abnormalities found in patients with PG without known preexisting immunodeficiency include cell-mediated abnormalities evidenced by anergy and absent in vitro mitogenic responses, abnormalities in neutrophil function, and monoclonal gammopathies. 14 The diagnosis of PG is generally made on the basis of clinical appearance of the ulcer and the exclusion of other possible causes for ulceration, particularly infectious causes, in a patient with immunodeficiency. The histologic appearance of PG is not diagnostic. A fully developed ulcer shows necrosis and a mixed inflammatory infiltrate that extends into the reticular dermis and sometimes into the subcutaneous tissue. The most common cutaneous ulcerative disease in AIDS is HSV infection. Although these lesions may become chronic in patients with immune deficiency, they typically begin as a vesicular eruption and do not develop a rolled border. A Tzanck smear of the base of the lesion or a positive viral culture for HSV usually confirms the diagnosis; both of these were negative in our two patients. Cytomegalovirus has rarely been reported to cause ulceration; however, it is usually present as a mixed infection with Candida species, HSV, atypical mycobacteria, or staphylococci. 15 Varicella-zoster virus may also cause a necrotic ulcer in children infected with HIV, 16 but biopsy of the margin of the ulcerative lesions in our patients failed to reveal multinucleated giant cells or intranuclear inclusions, and cultures for varicella-zoster virus were negative. Ecthyma gangrenosum, a cutaneous manifestation of systemic P. aeruginosa infection, may cause ulceration but rapidly becomes necrotic with surrounding induration. Furthermore, ecthyma gangrenosum is a necrotizing vasculitis histologically, with gram-negative bacilli within the walls of small arteries and
Pyoderma gangrenosum in pediatric A I D S
65
l a b l e . Disorders associated with PG in children* lmmunodeficiencydisorders Hypogammaglobulinemia IgA deficiency Impaired leukocyte function HIV infection Inflammatory disorders Arthritis Crohn disease Ulcerative colitis Takayasu arteritis Neoplasia Leukemia Miscellaneous Congenital heart disease *Data from references 2 to 8.
veins. Histoplasmosis may cause ulcerative cutaneous lesions in patients with AIDS, but biopsy specimens reveal granulomatous dermal infiltrates with intracytoplasmic yeast.iv Likewise, ulcerative lesions of sporotrichosis in patients with AIDS show suppurative granulomatous dermal infiltrates with spores, is These infectious causes of ulceration can be distinguished from PG by their clinical and histopathologic appearance, special stains of biopsy sections, and cultures for pathogens. Local therapy of PG is rarely effective when used alone in children, 1 but compresses and topical antibiotic ointments are often a useful adjuvant to systemic therapy. Both topical and intralesional corticosteroids have been used to decrease the inflammation that surrounds the ulcer. D6bridement of ulcerations or the application of irritating materials such as 20% benzoyl peroxide may aggravate the condition. Oxygen-permeable and semipermeable dressings may prove useful in minimizing trauma and improving wound healing for patients without secondary bacterial infections. For patients who do not respond to local treatment, TM 19 dapsone or sulfapyridine and prednisone are most commonly used. TM 19 These agents should be tried before alternate therapies such as pulsed corticosteroid therapy, 2~ minocycline, rifampin, clofazamine, 11 cyclophosphamide,21 cyclosporine, azathioprine, melphalan, cytosine arabinoside, daunorubicin, mercaptopurine,22 or thalidomide23 are administered. Systemic antibiotic therapy is useful for secondary bacterial infections. Skin grafts are frequently rejected and may induce new lesions of PG. In children PG is rare and may indicate a serious underlying systemic disorder such as inflammatory bowel disease, arthritis, leukemia, or HIV infection. The children we describe fit the Centers for Disease Control criteria for HIV infection.24 In an HIV-infected child with an ulcer, a vig-
66
Paller et aL
orous investigation must be undertaken to exclude a treatable infectious agent such as H S V , bacteria, fungi, or mycobacteria.
REFERENCES 1. Powell FC, Perry HO. Pyoderma gangrenosum in childhood. Arch Dermatol 1984;120:757-61. 2. Sourreil MP, Beylot C, Boisseau M, et al. Pyodermite phag6d6nique du si6ge et des organes g~nitaux chez un nourrisson de un mois et demi hypogammaglobulin6mique. Bord Med 1970;3:2462-4. 3. Barri~re H, Litoux P, Stalder JF, et al. Pyoderma gangrenosum au cours d'une hypogammaglobulin6miecong6nitale. Ann Dermatol Venereol 1979;108:695-6. 4. Stritzler C. Artresia of left nostril and deformity of upper lip following pyoderma gangrenosum of left upper lip, in a patient with hypogammaglobulinemia [Letter]. Arch Dermatol 1957; 36:366. 5. Guilhou J J, Guillot B, Meynadier J. Pyoderma gangrenosum: quatorze observations personelles et revue de la litt6rature [Letter]. J Mal Vase 1987;12:202-7. 6. Choulot J J, Saint Martin J. Pyoderma gangrenosum associ6 ~i un d6ficit en IgA. Ann Pediatr 1987;34:252. 7. Bundino S, Zina AM. Pyoderma gangrenosum associated with selective hereditary IgA deficiency. Dermatologica 1984;168: 230-2. 8. Hodgson G, Thompson E. Chronic repetitive suppurations of skin associated with a serum factor affecting bactericidal capacity of polymorphonuclear leukocytes. Proc R Soc Med 1972;65:691-2. 9. Anderson DC, Springer TA. Leukocyte adhesion deficiency. Ann Rev Med 1987;38:175-94. 10. Kluin-Nelemans JC, Ramselaar CG. Hepatic abscesses, pyoderma gangrenosum-like dermatitis and IgA immune complexes: a presentation of chronic granulomatous disease in an adult, Neth J Med 1982;25:100-4. 11. Berbis P, Mege JL, Capo C, Kaplanski S, Bongrand P, Privat Y. Hyperimmunoglobulin E and impaired neutrophil functions in a case of pyoderma gangrenosum: effect of clofazimine. J Am Acad Dermatol 1988;18:574-6.
The Journal of Pediatrics July 1990
12. Schwaegerle SM, Bergfeld WF, Senitzer D, Tidrick RT. Pyoderma gangrenosum: a review. J Am Acad Dermatol 1988;18:559-68. 13. Schwartz BK, Clendenning WE, Blasik LG. Pyoderma gangrenosum in a patient with HTLV-II1 antibody. Arch Dermatol 1986;122:508-9. 14. Prystowsky JH, Kahn SN, Lazarus GS. Present status of pyoderma gangrenosum: review of 21 cases. Arch Dermatol 1989;125:57-64. 15. Lee JY. Cytomegalovirus infection involving the skin in immunocompromised hosts. Am J Clin Pathol 1989;92:96100. 16. Jura E, Chadwick EG, Josephs SH, et al. Varicella-zoster virus infections in children infected with human immunodeficiency virus. Pediatr Infect Dis 1989;8:586-90. 17. Hazelhurst JA, Vismer HF. Histoplasmosis presenting with unusual skin lesions in acquired immunodeficiency syndrome (AIDS). Br J Dermatol 1985;113:345-8. 18. Shaw JC, Levinson W, Montanaro A. Sporotrichosis in the acquired immunodeficiency syndrome. J Am Acad Dermatol 1989;21:1145-7. 19. Soto LD. Diaminodiphenylsulfone and steroids in the treatment of pyoderma gangrenosum. Int J Dermatol 1970;9:293300. 20. Johnson RB, Lazarus GS. Pulse therapy: therapeutic efficacy in the treatment of pyoderma gangrenosum. Arch Dermatol 1982;118:76-84. 21. Crawford SE, Sherman R, Favara B. Pyoderma gangrenosum with response to cyclophosphamide therapy. J PEDIATR 1967;71:255-8. 22. Maldonado N, Torres VM, Mendez-Cashion D, et al. Pyoderma gangrenosum treated with 6-mercaptopurine and followed by acute leukemia. J PED1ATR 1968;72:409-14. 23. Venencie PY, Saurat JH. Pyoderma gangrenosum chez un enfant. traitement par la thaliodomide. Ann Pediatr 1982;29: 67-9. 24, Centers for Disease Control. Classification system for human immunodeficiency virus (HIV) infection in children under 13 years of age. MMWR 1987;36:225-30.
We describe two children with human immunodeficiency virus infection in whom pyoderma gangrenosum developed. Although pyoderma gangrenosum most commonly occurs in children with inflammatory bowel disease, it has also been described in patients with a variety of immunodeficiencies. In such patients a vigorous search to exclude a treatable infection should be m a d e before the lesions are treated as pyoderma gangrenosum. (J PEDIATR1990;117:63-6)
Although pyoderma g a n g r e n o s u m has been described in patients with a variety of immunodeficiency disorders, it has not been reported in a child with the acquired i m m u n o d e ficiency syndrome. W e have observed two children with P G and h u m a n immunodeficiency virus infection. Because of the unusual manifestations of infectious disorders in patients with A I D S , including atypical ulcerations, it is important to eliminate possible infectious causes before concluding t h a t a patient has PG. CASE R E P O R T S Patient 1. A 5-year-old black boy, born in 1984 after a 28-week gestation, weighed 1121 gm at birth. He had neonatal asphyxia and ventricular hemorrhage and required oxygen and ventilation for the first 3 tA months of life. During this period he had multiple cardiac arrests and a cerebrovascular accident, and received multiple blood transfusions. For the first 3 years of life he was clinically well except for panhypopituitarism diagnosed at 7 months of age. As a resuit, he was severely growth retarded and received hydrocortisone and levothyroxine daily and somatrem twice weekly. At 3V2 years of age the patient was kicked in the left preauricular area. Shortly thereafter an ulcer developed at the site and slowly enlarged. Three months after onset, examination revealed a well-circumscribed ulceration with a purulent base and a slightly rolled border that surrounded the ear. A biopsy specimen of the ulSubmitted for publication Jan. 8, 1990; accepted Feb. 9, 1990. Reprint requests: Amy S. Paller, MD, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614. 9/20/20029
cer border showed absence of epidermis and a mixed inflammatory cell dermal infiltrate with no evidence of vasculitis or granulomas. Special stains for bacteria, fungi, and mycobacteria were negative. The ulcer was treated with compresses and polymyxin B-bacitracin ointment, without improvement. Because of the association of PG and inflammatory bowel disease, x-ray examination of the upper gastrointestinal tract, with small bowel follow-through, was performed; results were normal. After two episodes of bacteremic Streptococcus pneumoniae pneumonia, testing for HIV infection was performed and showed the presence of HIV antibodies by both enzyme-linked immunosorbent assay and Western blot assay.
AIDS CMV H1V HSV PG
Acquired immunodeficiency syndrome Cytomegalovirus Human immunodeficiency virus Herpes simplex virus Pyoderma gangrenosum
The patient was first seen at Children's Memorial Hospital 6 months after the ulcer initially developed. By this time the ulcer had enlarged considerably (Fig. 1). Biopsy material was obtained for culture and yielded no aerobic or anaerobic bacteria, fungi, or mycobacteria. Viral cultures of the base of the lesion were negative for herpes simplex virus and varicella-zoster virus. The patient had a concurrent herpetic infection of the lower lip, which responded well to intravenous administration of acyelovir, and a paronychia of the thumb caused by Candida albicans, which responded to treatment with compresses, topica ! econazole, and systemic ketoconazole. The ulcer was again treated with compresses and polymyxin Bbacitracin ointment, and the area was kept wrapped to avoid dis-
63
64
Paller et al.
The Journal o f Pediatrics July 1990
Fig. 2. Case 2. Pyoderma gangrenosum of mons pubis. Fig. 4. Case 1. Periauricular PG at site of trauma, unresponsive to local therapy.
ruption by the child. The ulcer began to heal during three hospitalizations for pneumonia but repeatedly enlarged while at home. Eleven months after the initial ulcer developed, the child was readmitted with right periorbital cellulitis and a new purulent ulcer on the right eyelid. Dapsone therapy, 12.5 mg twice daily, was initiated, in addition to compresses and topical antibiotics to both ulcers. Within 1 week the eyelid lesion had fully resolved, leaving only a small scar, and the periauricular ulceration showed significant reepithelialization. Two months after the initiation of dapsone therapy, the periauricular ulcer was virtually healed. The patient died suddenly at 5 years of age, while still taking dapsone, of bacterial pneumonia. Patient 2. In a 9-month-old black girl with an unremarkable medical history, except for thrush at age 6 months, an erythematous papule with a blister developed on the mons pubis. Despite antibiotic therapy, this lesion enlarged and ulcerated. A similar lesion developed on the inferior aspect of the right buttock. When fever developed, the child was admitted to the Medical University of South Carolina for examination. On admission the patient had a temperature of 38.5 ~ C and was at less than the 5th percentile for height and weight. She had two ulcers, measuring 2.5 x 3.0 cm on the mons pubis and 1.5 x 1.5 cm in the right perianal region. The ulcers were surrounded by a bluish purple, overhanging border and by an erythematous, 5.0 mm rim (Fig. 2). The center of the larger ulcer was covered with a dried black eschar. Other significant findings included submandibular and inguinal lymphadenopathy, and the liver was palpable 8 cm below the costal margin at the midclavicular line. Cultures from the ulcers revealed scant growth of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Enterococcus species, consistent with fecal contamination. Because of the failure to thrive, lymphadenopathy, and hepatornegaly, HIV antibody titers were measured and were positive by enzyme-linked im-
munosorbent assay and Western blot analysis. T cell subsets showed a decreased T4/T8 ratio of 0.5, and the patient had panhyperglobutinemia. Subsequently, the patient's mother was also found to have HIV antibody by Western blot analysis. The patient was treated with intravenous nafcillin and gentamicin, but the ulcers continued to enlarge. A biopsy specimen of the ulcer on the mons pubis revealed necrosis of the epidermis and underlying dermis but no evidence of epidermal viral cytopathic changes. In the adjacent subcutaneous tissue and dermis were mixed infiltrates of polymorphonuclear leukocytes, lymphocytes, histiocytes, and plasma cells. No evidence of vasculitis or granulomatous inflammation was present. Stains for bacteria, fungi, and mycobacteria revealed no organisms. Cultures of tissue for HSV and varicella-zoster virus were negative. Wet compresses, topical corticosteroids, mupirocin ointment, zinc oxide paste, and protective padding to prevent further trauma from diapers were applied. The ulcers began to heal, and at the time of the patient's discharge 3 weeks later, both ulcers and the biopsy site had healed almost completely. When the patient was 15V2 months of age, results of a repeated HIV antibody tests remained positive and the T4/T8 ratio had decreased further to 0.2. DISCUSSION P y o d e r m a g a n g r e n o s u m is an u n c o m m o n ulcerative skin condition with a distinctive clinical a p p e a r a n c e . It o f t e n begins as a pustule, bulla, or fluctuant n o d u l e that ruptures, f o r m i n g a rapidly enlarging ulcer with a m u c o p u r u l e n t base. T h e m a r g i n o f the ulcer is violaceous a n d u n d e r m i n e d , a n d b e c o m e s m o r e dusky in color as it ages. Lesions a r e most f r e q u e n t l y found on t h e a n t e r i o r a s p e c t o f the legs b u t also occur on t h e face, trunk, and buttocks. T w e n t y p e r c e n t o f p a t i e n t s have a history o f t r a u m a to t h e involved site ( p a t h e r g y ) , as in our patients. T h e ulcer o f t e n heals with an a t r o p h i c or c r i b r i f o r m scar.
Volume 117 Number 1, Part 1
Only 4% of patients with PG are younger than 15 years of ag e.1 Although idiopathic in 17% of reported cases, PG in children may be associated with a variety of underlying systemic disorders 28 (Table). The most common associations in children are inflammatory bowel disease and arthritis. Pyoderma gangrenosum-like ulcers are a common problem in children with leukocyte adhesion deficiencies,9 but bacterial cultures of lesions yield Staphylococcus aureus and, less commonly, gram-negative organisms. Adults with PG and other primary immunodeficiency disorders, including chronic granulomatous disease 1~ and the hyperimmunoglobulinemia E syndrome, 11 have also been described. Although the cause of PG is unknown, its association with this variety of underlying disorders suggests that it is related to host immunologic defects. 12 It was recently reported in a 23-year-old homosexual man with HIV infection, but the ulcers developed 6 years before the antibody testing was performed and the patient had no signs or symptoms of AIDS or AIDS-related complex at the time of antibody testing.13 The immune abnormalities found in patients with PG without known preexisting immunodeficiency include cell-mediated abnormalities evidenced by anergy and absent in vitro mitogenic responses, abnormalities in neutrophil function, and monoclonal gammopathies. 14 The diagnosis of PG is generally made on the basis of clinical appearance of the ulcer and the exclusion of other possible causes for ulceration, particularly infectious causes, in a patient with immunodeficiency. The histologic appearance of PG is not diagnostic. A fully developed ulcer shows necrosis and a mixed inflammatory infiltrate that extends into the reticular dermis and sometimes into the subcutaneous tissue. The most common cutaneous ulcerative disease in AIDS is HSV infection. Although these lesions may become chronic in patients with immune deficiency, they typically begin as a vesicular eruption and do not develop a rolled border. A Tzanck smear of the base of the lesion or a positive viral culture for HSV usually confirms the diagnosis; both of these were negative in our two patients. Cytomegalovirus has rarely been reported to cause ulceration; however, it is usually present as a mixed infection with Candida species, HSV, atypical mycobacteria, or staphylococci. 15 Varicella-zoster virus may also cause a necrotic ulcer in children infected with HIV, 16 but biopsy of the margin of the ulcerative lesions in our patients failed to reveal multinucleated giant cells or intranuclear inclusions, and cultures for varicella-zoster virus were negative. Ecthyma gangrenosum, a cutaneous manifestation of systemic P. aeruginosa infection, may cause ulceration but rapidly becomes necrotic with surrounding induration. Furthermore, ecthyma gangrenosum is a necrotizing vasculitis histologically, with gram-negative bacilli within the walls of small arteries and
Pyoderma gangrenosum in pediatric A I D S
65
l a b l e . Disorders associated with PG in children* lmmunodeficiencydisorders Hypogammaglobulinemia IgA deficiency Impaired leukocyte function HIV infection Inflammatory disorders Arthritis Crohn disease Ulcerative colitis Takayasu arteritis Neoplasia Leukemia Miscellaneous Congenital heart disease *Data from references 2 to 8.
veins. Histoplasmosis may cause ulcerative cutaneous lesions in patients with AIDS, but biopsy specimens reveal granulomatous dermal infiltrates with intracytoplasmic yeast.iv Likewise, ulcerative lesions of sporotrichosis in patients with AIDS show suppurative granulomatous dermal infiltrates with spores, is These infectious causes of ulceration can be distinguished from PG by their clinical and histopathologic appearance, special stains of biopsy sections, and cultures for pathogens. Local therapy of PG is rarely effective when used alone in children, 1 but compresses and topical antibiotic ointments are often a useful adjuvant to systemic therapy. Both topical and intralesional corticosteroids have been used to decrease the inflammation that surrounds the ulcer. D6bridement of ulcerations or the application of irritating materials such as 20% benzoyl peroxide may aggravate the condition. Oxygen-permeable and semipermeable dressings may prove useful in minimizing trauma and improving wound healing for patients without secondary bacterial infections. For patients who do not respond to local treatment, TM 19 dapsone or sulfapyridine and prednisone are most commonly used. TM 19 These agents should be tried before alternate therapies such as pulsed corticosteroid therapy, 2~ minocycline, rifampin, clofazamine, 11 cyclophosphamide,21 cyclosporine, azathioprine, melphalan, cytosine arabinoside, daunorubicin, mercaptopurine,22 or thalidomide23 are administered. Systemic antibiotic therapy is useful for secondary bacterial infections. Skin grafts are frequently rejected and may induce new lesions of PG. In children PG is rare and may indicate a serious underlying systemic disorder such as inflammatory bowel disease, arthritis, leukemia, or HIV infection. The children we describe fit the Centers for Disease Control criteria for HIV infection.24 In an HIV-infected child with an ulcer, a vig-
66
Paller et aL
orous investigation must be undertaken to exclude a treatable infectious agent such as H S V , bacteria, fungi, or mycobacteria.
REFERENCES 1. Powell FC, Perry HO. Pyoderma gangrenosum in childhood. Arch Dermatol 1984;120:757-61. 2. Sourreil MP, Beylot C, Boisseau M, et al. Pyodermite phag6d6nique du si6ge et des organes g~nitaux chez un nourrisson de un mois et demi hypogammaglobulin6mique. Bord Med 1970;3:2462-4. 3. Barri~re H, Litoux P, Stalder JF, et al. Pyoderma gangrenosum au cours d'une hypogammaglobulin6miecong6nitale. Ann Dermatol Venereol 1979;108:695-6. 4. Stritzler C. Artresia of left nostril and deformity of upper lip following pyoderma gangrenosum of left upper lip, in a patient with hypogammaglobulinemia [Letter]. Arch Dermatol 1957; 36:366. 5. Guilhou J J, Guillot B, Meynadier J. Pyoderma gangrenosum: quatorze observations personelles et revue de la litt6rature [Letter]. J Mal Vase 1987;12:202-7. 6. Choulot J J, Saint Martin J. Pyoderma gangrenosum associ6 ~i un d6ficit en IgA. Ann Pediatr 1987;34:252. 7. Bundino S, Zina AM. Pyoderma gangrenosum associated with selective hereditary IgA deficiency. Dermatologica 1984;168: 230-2. 8. Hodgson G, Thompson E. Chronic repetitive suppurations of skin associated with a serum factor affecting bactericidal capacity of polymorphonuclear leukocytes. Proc R Soc Med 1972;65:691-2. 9. Anderson DC, Springer TA. Leukocyte adhesion deficiency. Ann Rev Med 1987;38:175-94. 10. Kluin-Nelemans JC, Ramselaar CG. Hepatic abscesses, pyoderma gangrenosum-like dermatitis and IgA immune complexes: a presentation of chronic granulomatous disease in an adult, Neth J Med 1982;25:100-4. 11. Berbis P, Mege JL, Capo C, Kaplanski S, Bongrand P, Privat Y. Hyperimmunoglobulin E and impaired neutrophil functions in a case of pyoderma gangrenosum: effect of clofazimine. J Am Acad Dermatol 1988;18:574-6.
The Journal of Pediatrics July 1990
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