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Instructive case report
86 Infectious Diseases Newsletter
respond to standard therapy. Perhaps we should also look harder at childhood pneumonia occurring in the summer and early fall. Mary L. Fried, Ph.D. Clinical Microbiologist Tucson Medical Center References i. 2. 3. 4. 5.
Anderson, RD, et al., J Infect Dis 143:386, 1981. Edelstein, PH, and Finegold, SM, J Clin Microbiol 10:141, 1979. Foy, HM, et al., Lancet i:7~7, 1979. Lattimer, GL, and Ormsbee, RA, Legionnaires' Disease. New York: Marcel Dekker 89 Inc., 1981. Orenstein, WA, et al., J Pediatr 99:403, 1981.
INSTRUCTIVE CASE REPORT We have taken care of a single patient who has presented an entire panoply of infectious diseases problems secondary to lymphatic malignancy and chemotherapy. The issues span several infectious agents and various immunologic and therapeutic strategies. For this reason, we will present his story in continuous fashion over the next three issues (Dr. John Hutter, our oncologist, has been M.R.'s physician for the past five years). Case Report M.R., an 8-year-old male, developed Hodgkin's disease of mixed cellularity in November 1977. He had diffuse node involvement including axillary, inguinal, iliac, and peri-aortic. He was assessed stage III-A, and was found to have splenic hilar nodes and hepatic involvement and a splenectomy was performed with multiple areas of lymphoma revealed. He was initially treated with mustard, vincristine, prednisone, and procarbazine (MOPP) in a standardized protocol and subsequently received regionalized radiotherapy. On May 7, 1978, he developed typical zoster (he had varicella at age 4) with a septic febrile pattern which became secondarily infected with S. aureus. He responded well to dicloxicillin and Ara-A with .complete recovery. Analysis At this point in his narrative illness, we'll pause to consider the pathogenesis, outcomes and therapeutic strategies in varicella-zoster infections.
M.R. developed recrudescence of his latent varicella infection which proceeded to a severe zosteriform eruption, successfully managed with adenosine arabinoside. Varicella virus, dormant in dorsal root ganglia, can be freed by a variety of influences from whatever immunologic control the host has to contain it in the latent stage. 1 In M.R.'s case, his disease, its chemotherapy and irradiation may singly or in combination have allowed release of the virus from immunologic control. Zoster occurs most commonly in Hodgkin's lymphoma (our patient) and in chronic lymphatic leukemia but can also occur in the various acute leukemias and lymphomas. 2 Of 104 patients studied at the National Institutes of Health, 34% had received radiation therapy prior to the onset of zoster; in two-thirds of these, zoster occurred in the dermatome served bY the irradiated dorsal root ganglia.3 Since most patients who are irradiated also receive chemotherapy, it m a y be impossible to sort out the specific cause. Zoster appears to be less virulent than primary varicella in the immunocompromised individual; the latter has a mortality of 4/60 in one series at St. Jude's. 4 In contrast, zoster is mainly self-limited, even in the immunocompromised; on occasion it can disseminate (approximately 15% do) and encephalitis can occur, which may be fatal. Zoster is not a preventable disease in the immunocompromised, rising as it does from a latent infection. Varicella-Zoster Immune Globulin (VZIG) can be of benefit in the non-immune exposed individual at high risk from primary varicella (see Volume 7, Number 3: February 1981 IDN). Therapy of varicella-zoster infections once they occur in such high risk children usually consists of a DNA-inhibitor, usually one of the analogs of the purine or pyrimidine nucleosides. Cytosine arabinoside, the first agent investigated, not only failed to help, it appeared to increase the length of the disease. 5 On the other hand, vidarabine (adenine arabinoside, Ara-A) had a marked beneficial effect in both zoster and primary varicella infections. 6 The short course of therapy results in few side effects of transient nature, when they do occur. Acyclovir, an analog of deoxyguanosine, is currently under investigation in varicella-zoster infections and may_ be more effective than Ara-A.;. Interferon at high dosage and specific
9 1982 by Elsevier Science Publishing Co., Inc.
87 Infectious Diseases N e w s l e t t e r
transfer factor also appear to have a beneficial effect but studies are limited. Ultimately, it is hoped that live varicella vaccine will provide lasting protection to high risk, susceptible patients. The saga of M.R. will con[inue in the next issue. 'Vincent A. Fulginiti, M.D. PKofessor and Head Department of Pediatrics Arizona Health Sciences Center References i.
2. 3. 4. 5. 6. 7.
Grose, C, ~.~Varicella-zoster virus infections, Chapter 3 in Human Herpes Virus Infections. Glaser, R and Stematsky, T (Eds), New York: Marcel Dekker, 1982. Dolin, R, Ann Intern Med 89:375, 1978. Mazur, MH, Dolin, R, Amer J Med 65:738, 1978. Feldman, S, et al., Pediatr 56:388, 1975. Stevens, DA, et al., N Engl J Med 289:873, 1973. Chren, LT, et al, J Infect Dis 133:A184, 1976. Selby, PJ, et al., Lancet ii:1267, 1979.
INTERNATIONAL .NOTES London: More than 900 persons aged 6 months to 88 years were examined for antibody t__o_o the three types of polioviruses. At least 95% Of persons older than 2 years had antibody to at least one serotype and 60% to all three. Children born between 1963 and 1968 had 80% to one type and 40% to all three types; the only exception to an otherwise uniform distribution. The exception is probably related to low acceptance rates for vaccine in that interval. These results suggest to the authors that a dose of OPV should be given to British children at school-leaving time. Brit Med J 284:697, 1982 Canada: Nicolle and coworkers at the University of Manitoba determined the rifampin susceptibility of H. influenzae type B after community wide ~se of rifamp~n in children and monocycline followed by rifampin in adults as chemoprophylaxis. The prophylaxis was given primarily for meningococcal disease. All H. influenzae strains were susceptible prior to chemoprophylaxis but 10.6%
were resistant one week into the effort and 7.5% at nine weeks after chemoprophylaxis ended. The numbers studied were small (106 at time 0, 29 at 1 week, and 67 at 9 weeks) and no clinical disease was reported. Antimicrob Agents Chemother 21:498, 1982 Egypt and Switzerland: Wahdan et al. conducted a field trial of living Salmonella typhi oral immunization. The strain used was attenuated as evidenced by no side effects when given to volunteers (3-10 x 106 live Salmonella). In previous small studies, a protective ratio of 87% was obtained against a high dose of virulent organisms. The trial was conducted in Egypt among 32,388 children split into placebo and vaccine groups. The dose was 1-8 x 109 organisms given three times every second day, after a dose of bicarbonate was given to prevent gastric acid destruction of the bacteria. Over a three-year follow-up period, 0nly 2 cases per 100,000 children per year were found in the vaccine group as opposed to 49 in the placebo group, a highly significant difference. No spread of vaccine bacilli was detected. J Infect Dis 145:292, 1982. Leiden r Holland: Slow, subcutaneous infusion of ordinary I.M. gammaglobulin was used in treatment of antibody deficiency by Roord and coworkers. Patients administered the treatments themselves using a scalp vein needle and an infusion pump. Each week 15-25 ml of GG were given at the rate of 2-3 ml/hour, sometimes during sleep (at least 50 mg IgG/kg/week). Serial IgG levels rose steadily and no significant side effects were observed, including three patients in whom anaphylactic reactions to I.M. injections had been experienced. Patients were said to prefer this method. Although no new infections were encountered, the interval of observation postinitiation of treatment was brief. Lancet i:689, 1982 NATIONAL NOTES Alabama: Septic neonates may display acute distention of the gallbladder (hydrops). Eight infants with either proved group B strep sepsis or suspected sepsis had hydrops; five responded to medicine Rx, two required surgery, and one died. Arch Dis Child 57:75, 1982 Philadelphia: A 20-year-old woman had an acute onset of sepsis with H. influenzae, type B superimposed on chronic pulmonary and upper respiratory tract infection secondary to selective
9 1982 by ElsevierScience PublishlrrgCo., Inc.
respond to standard therapy. Perhaps we should also look harder at childhood pneumonia occurring in the summer and early fall. Mary L. Fried, Ph.D. Clinical Microbiologist Tucson Medical Center References i. 2. 3. 4. 5.
Anderson, RD, et al., J Infect Dis 143:386, 1981. Edelstein, PH, and Finegold, SM, J Clin Microbiol 10:141, 1979. Foy, HM, et al., Lancet i:7~7, 1979. Lattimer, GL, and Ormsbee, RA, Legionnaires' Disease. New York: Marcel Dekker 89 Inc., 1981. Orenstein, WA, et al., J Pediatr 99:403, 1981.
INSTRUCTIVE CASE REPORT We have taken care of a single patient who has presented an entire panoply of infectious diseases problems secondary to lymphatic malignancy and chemotherapy. The issues span several infectious agents and various immunologic and therapeutic strategies. For this reason, we will present his story in continuous fashion over the next three issues (Dr. John Hutter, our oncologist, has been M.R.'s physician for the past five years). Case Report M.R., an 8-year-old male, developed Hodgkin's disease of mixed cellularity in November 1977. He had diffuse node involvement including axillary, inguinal, iliac, and peri-aortic. He was assessed stage III-A, and was found to have splenic hilar nodes and hepatic involvement and a splenectomy was performed with multiple areas of lymphoma revealed. He was initially treated with mustard, vincristine, prednisone, and procarbazine (MOPP) in a standardized protocol and subsequently received regionalized radiotherapy. On May 7, 1978, he developed typical zoster (he had varicella at age 4) with a septic febrile pattern which became secondarily infected with S. aureus. He responded well to dicloxicillin and Ara-A with .complete recovery. Analysis At this point in his narrative illness, we'll pause to consider the pathogenesis, outcomes and therapeutic strategies in varicella-zoster infections.
M.R. developed recrudescence of his latent varicella infection which proceeded to a severe zosteriform eruption, successfully managed with adenosine arabinoside. Varicella virus, dormant in dorsal root ganglia, can be freed by a variety of influences from whatever immunologic control the host has to contain it in the latent stage. 1 In M.R.'s case, his disease, its chemotherapy and irradiation may singly or in combination have allowed release of the virus from immunologic control. Zoster occurs most commonly in Hodgkin's lymphoma (our patient) and in chronic lymphatic leukemia but can also occur in the various acute leukemias and lymphomas. 2 Of 104 patients studied at the National Institutes of Health, 34% had received radiation therapy prior to the onset of zoster; in two-thirds of these, zoster occurred in the dermatome served bY the irradiated dorsal root ganglia.3 Since most patients who are irradiated also receive chemotherapy, it m a y be impossible to sort out the specific cause. Zoster appears to be less virulent than primary varicella in the immunocompromised individual; the latter has a mortality of 4/60 in one series at St. Jude's. 4 In contrast, zoster is mainly self-limited, even in the immunocompromised; on occasion it can disseminate (approximately 15% do) and encephalitis can occur, which may be fatal. Zoster is not a preventable disease in the immunocompromised, rising as it does from a latent infection. Varicella-Zoster Immune Globulin (VZIG) can be of benefit in the non-immune exposed individual at high risk from primary varicella (see Volume 7, Number 3: February 1981 IDN). Therapy of varicella-zoster infections once they occur in such high risk children usually consists of a DNA-inhibitor, usually one of the analogs of the purine or pyrimidine nucleosides. Cytosine arabinoside, the first agent investigated, not only failed to help, it appeared to increase the length of the disease. 5 On the other hand, vidarabine (adenine arabinoside, Ara-A) had a marked beneficial effect in both zoster and primary varicella infections. 6 The short course of therapy results in few side effects of transient nature, when they do occur. Acyclovir, an analog of deoxyguanosine, is currently under investigation in varicella-zoster infections and may_ be more effective than Ara-A.;. Interferon at high dosage and specific
9 1982 by Elsevier Science Publishing Co., Inc.
87 Infectious Diseases N e w s l e t t e r
transfer factor also appear to have a beneficial effect but studies are limited. Ultimately, it is hoped that live varicella vaccine will provide lasting protection to high risk, susceptible patients. The saga of M.R. will con[inue in the next issue. 'Vincent A. Fulginiti, M.D. PKofessor and Head Department of Pediatrics Arizona Health Sciences Center References i.
2. 3. 4. 5. 6. 7.
Grose, C, ~.~Varicella-zoster virus infections, Chapter 3 in Human Herpes Virus Infections. Glaser, R and Stematsky, T (Eds), New York: Marcel Dekker, 1982. Dolin, R, Ann Intern Med 89:375, 1978. Mazur, MH, Dolin, R, Amer J Med 65:738, 1978. Feldman, S, et al., Pediatr 56:388, 1975. Stevens, DA, et al., N Engl J Med 289:873, 1973. Chren, LT, et al, J Infect Dis 133:A184, 1976. Selby, PJ, et al., Lancet ii:1267, 1979.
INTERNATIONAL .NOTES London: More than 900 persons aged 6 months to 88 years were examined for antibody t__o_o the three types of polioviruses. At least 95% Of persons older than 2 years had antibody to at least one serotype and 60% to all three. Children born between 1963 and 1968 had 80% to one type and 40% to all three types; the only exception to an otherwise uniform distribution. The exception is probably related to low acceptance rates for vaccine in that interval. These results suggest to the authors that a dose of OPV should be given to British children at school-leaving time. Brit Med J 284:697, 1982 Canada: Nicolle and coworkers at the University of Manitoba determined the rifampin susceptibility of H. influenzae type B after community wide ~se of rifamp~n in children and monocycline followed by rifampin in adults as chemoprophylaxis. The prophylaxis was given primarily for meningococcal disease. All H. influenzae strains were susceptible prior to chemoprophylaxis but 10.6%
were resistant one week into the effort and 7.5% at nine weeks after chemoprophylaxis ended. The numbers studied were small (106 at time 0, 29 at 1 week, and 67 at 9 weeks) and no clinical disease was reported. Antimicrob Agents Chemother 21:498, 1982 Egypt and Switzerland: Wahdan et al. conducted a field trial of living Salmonella typhi oral immunization. The strain used was attenuated as evidenced by no side effects when given to volunteers (3-10 x 106 live Salmonella). In previous small studies, a protective ratio of 87% was obtained against a high dose of virulent organisms. The trial was conducted in Egypt among 32,388 children split into placebo and vaccine groups. The dose was 1-8 x 109 organisms given three times every second day, after a dose of bicarbonate was given to prevent gastric acid destruction of the bacteria. Over a three-year follow-up period, 0nly 2 cases per 100,000 children per year were found in the vaccine group as opposed to 49 in the placebo group, a highly significant difference. No spread of vaccine bacilli was detected. J Infect Dis 145:292, 1982. Leiden r Holland: Slow, subcutaneous infusion of ordinary I.M. gammaglobulin was used in treatment of antibody deficiency by Roord and coworkers. Patients administered the treatments themselves using a scalp vein needle and an infusion pump. Each week 15-25 ml of GG were given at the rate of 2-3 ml/hour, sometimes during sleep (at least 50 mg IgG/kg/week). Serial IgG levels rose steadily and no significant side effects were observed, including three patients in whom anaphylactic reactions to I.M. injections had been experienced. Patients were said to prefer this method. Although no new infections were encountered, the interval of observation postinitiation of treatment was brief. Lancet i:689, 1982 NATIONAL NOTES Alabama: Septic neonates may display acute distention of the gallbladder (hydrops). Eight infants with either proved group B strep sepsis or suspected sepsis had hydrops; five responded to medicine Rx, two required surgery, and one died. Arch Dis Child 57:75, 1982 Philadelphia: A 20-year-old woman had an acute onset of sepsis with H. influenzae, type B superimposed on chronic pulmonary and upper respiratory tract infection secondary to selective
9 1982 by ElsevierScience PublishlrrgCo., Inc.