1056
Correspondence
References
I. Segreti J, Gootz TO, Goodman U, et al. High-level quinolone resistance in clinical isolates of Campylobacter jejuni. J Infect Dis 1992; 165:667-70. 2. Adler-Mosca H, Luthy-Hottenstein J, Lucchini GM, Burnens A, AltweggM. Development of resistance to quinolones in five patients with
Another Case of Pneumocystis carinii Pneumonia in a Patient with Dyskeratosis Congenita (Zinsser-Cole-Engman Syndrome)
campylobacteriosis treated with norftoxacin or ciproftoxacin. Eur J Clin Microbiol Infect Dis 1991;10:953-7. 3. Rautelin H, Renkonen OV, Kosunen TV. Emergence of ftuoroquinolone resistance in Campylobacter jejuni and Campylobacter coli in subjects from Finland. Antimicrob Agents Chemother 1991;35:2065-9. 4. Wistrom J, Jertborn M, Ekwall E, et al. Empiric treatment of acute diarrheal disease with norfloxacin. A randomized, placebo-controlled trial. Ann Intern Med 1992; 117:202-8.
treatment, and extensive culturing (including that for viruses) and serological testing failed to identify any other organism. Results ofa serological test for HIV were negative. While receiving ventilatory support, he developed rapid progressive pulmonary insufficiency with diffuse pulmonary infiltrates and severe hypoxemia. Repeated examination of bronchoalveolar lavage fluid for Pneumocystis organisms was not diagnostic until 24 hours before the patient died. Because of severe thrombocytopenia, transbronchial or open lung biopsies had not been performed. Autopsy revealed fibrinous pleuritis; focal areas with pulmonary hemorrhage; and abundant, intensely eosinophilic, foamy, honeycombed material that completely filled the interalveolar septa and was positive for the periodic acid-Schiff reaction. In Grocott-Gomori methenamine-silver nitrate stains, typical P. carinii cysts and trophozoites could be seen. No other organisms were identified in the lungs or in other organs. Further pertinent findings were lymphocyte depletion with a lack of lymph follicles in prominent paratracheal and paraaortic lymph nodes, a reduction of the white pulp of the spleen, and strikingly hypocellular bone marrow with near absence of megakaryocytes. Dyskeratosis congenita is a rare inherited disorder of which ,..., 100 cases have been described in the literature since the first report by Zinsser in 1906. Patients with the syndrome present with certain typical dermatologic features, ofwhich dystrophy or absence of the nails (figure I) and hyperkeratosis with areas of hypopigmentation and reticular hyperpigmentation become clinically prominent early in the course of the disease [2]. Many patients develop complications in the second and third decades
Correspondence: Dr. Winfried V. Kern, Medizinische Universitatsklinik und Poliklinik, Postfach 38 80, 0-7900 VIm, Germany. Clinical Infectious Diseases 1992;15:1056-7 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1506-0030$02.00
Figure 1. Complete loss of fingernails in a patient with dyskeratosis congenita.
Downloaded from http://cid.oxfordjournals.org/ at University of Exeter on August 1, 2015
SIR-Pneumocystis carinii pneumonia is a well-known lifethreatening complication of a variety of acquired or primary immunodeficiency disorders [1]. Outside the population of those infected with human immunodeficiency virus (HIV), the infection is most frequently diagnosed in children with acute lymphocytic leukemia and in organ or bone marrow-transplant recipients. We present the case of P. carinii pneumonia developing in a patient with dyskeratosis congenita (Zinsser-Cole-Engman syndrome), a rare multisystem disorder characterized by typical dermatologic lesions [2]. A 34-year-old man was admitted because of severe dyspnea, cachexia, and low-grade fever. At the age of 12 years, he was found to have dyskeratosis congenita. When he was 16 years old, mild thrombocytopenia was noted. He was well until a few years before admission, when he had complained of recurrent episodes of wheezing and unproductive cough and of weight loss. A limited diagnostic workup at that time revealed both restrictive and obstructive pulmonary abnormalities, and discrete bilateral reticular infiltrates were evident on chest radiographs. He was given intermittent medication including systemic steroids for presumed allergic asthma. On admission, the patient had bicytopenia and restrictive lung abnormalities with evidence of airflow obstruction. The chest radiograph showed bilateral reticular and nodular infiltrates including the lung base. Shortly after admission, the patient developed acute airway obstruction, with pneumomediastinum extending to the neck and parapharyngeal space, and a small pneumothorax. He refused any invasive diagnostic evaluation. Conservative treatment including repeated administration of steroids because of apparent airway obstruction eventually failed, and the patient was intubated. The subsequent hospital course was characterized by severe thrombocytopenia with spontaneous bleeding, mild neutropenia and lymphopenia, repeated extubation failures with tracheobronchitis, and excessive oropharyngeal inflammation due to Staphylococcus aureus. He was given adequate antibacterial
CID 1992; 15 (December)
CID 1992;15 (December)
Correspondence
Effects of Antimalarial Chemoprophylactic Agents on the Viability of the Ty21a Typhoid Vaccine Strain SIR-An increase in travel to the developing world has brought about a greater concern for the prevention of illnesses that may be acquired abroad. The attenuated Ty2la oral typhoid vaccine (Vivotif; Berna, Berne, Switzerland) is often recommended because its efficacy is comparable to that of the inactivated injectable vaccine and it is associated with a relative lack of adverse effects [I]. Because areas of the world where typhoid fever is endemic may coincide with areas where chloroquine-resistant Plasmodium falciparum malaria is endemic, pretravel recommendations for protection in these regions often call for weekly
This work was presented at the Annual Meeting of the American Society of Tropical Medicine and Hygiene held on 1-6 December 1991 in Boston. Mefloquine powder was provided by the Department of Medicinal Chemistry, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, D.C. Correspondence: Dr. Phyllis E. Kozarsky, Emory University School of Medicine, Emory Crawford Long Hospital. Division oflnfectious Diseases, 20 Linden Avenue, Atlanta, Georgia 30365. Clinical Infectious Diseases 1992;15:1057-8 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1506-0031$02.00
Christian Rose and Winfried V. Kern Department ofPathology and Section ofInfectious Diseases, Ulm University Hospital and Medical Center, VIm, Germany
References I. Walzer PD, Kim CK, Cushion MT. Pneumocystis carinii. In: Walzer PD, Genta RM, eds. Parasitic infections in the compromised host. New York: Marcel Dekker, 1989:83-178. 2. Sirinavin C, Trowbridge AA. Dyskeratosis congenita: clinical features and genetic aspects. Report of a family and review of the literature. J Med Genet 1975; 12:339-55. 3. Bundino S, Zina AM, Bernengo MG. Dyskeratosis congenita with epidermodysplasia verruciformis of Lewandowsky and Lutz. Dermatologica 1978; 156: 15-23. 4. Wiedemann HP, McGuire J, Dwyer JM, et al. Progressive immune failure in dyskeratosis congenita. Report ofan adult in whom Pneumocystis carinii pneumonia and fatal disseminated candidiasis developed. Arch Intern Med 1984;144:397-9. 5. Giannetti A, Seidenari S. Deficit of cell-mediated immunity, chromosomal alterations and defective DNA repair in a case of dyskeratosis congenita. Dermatologica 1980; 160: 113-7. 6. Scoggins RB, Prescott KJ, Asher GH, Blaylock WK, Bright R W. Dyskeratosis congenita with Fanconi-type anemia: investigations ofimmunologic and other defects. Clin Res 1971; 19:409. 7. Kawaguuchi K, Sakamaki H, Onozawa Y, Koike M. Dyskeratosis congenita (Zinsser-Cole-Engman syndrome). An autopsy case presenting with rectal carcinoma, non-cirrhotic portal hypertension, and Pneumocystis carinii pneumonia. Virchows Archiv [AJ 1990;417:247-53.
administration of mefloquine beginning I week before travel in addition to administration of the typhoid vaccine [2]. The Ty2la vaccine strain requires active replication in the host gastrointestinal tract for development of immunity [3]. Unfortunately, there has been concern that some antimalarial agents may have antibacterial activity and thus may blunt the immune response if given concurrently with the oral typhoid vaccine [4, 5]. In fact, in vitro data have shown mefloquine to have activity against the cell membrane of some gram-negative organisms [6], and a more recent study of Ambrosch et al. [4] suggested that mefloquine taken 12 hours before the oral typhoid vaccine would interfere with serum antibody response to the vaccine. Although it is unknown whether serum antibody response to the vaccine correlates with protection, this response may be a marker; thus, interference is of concern. Because published data in this area are scant, recommendations concerning the timing of administration of the four everyother-day doses of typhoid vaccine and the start of weekly mefloquine prophylaxis vary. The current Vivotif package insert fails to address the potential problem. In recent discussions with the manufacturer, it was suggested that one wait only 18-24 hours after taking mefloquine before beginning the vaccine course (personal communication; S. Cryz, Swiss Serum and Vaccine Institute, Berne, Switzerland). On the other hand, the Enteric Diseases Branch of the Centers for Disease Control in
Downloaded from http://cid.oxfordjournals.org/ at University of Exeter on August 1, 2015
of their life. Mucosal leukoplakia and carcinoma have frequently been reported. Progressive bone marrow hypoplasia (usually beginning with thrombocytopenia) is another frequent complication. Infections ofdyskeratosis congenita, descriptions of which are often taken from the patients' histories and are therefore poor, have been attributed to leukopenia in some reports [2]. Recent data, however, suggest a rather complex immunodeficiency with severely impaired cellular immunity in patients with the syndrome [3-6]. Lymphopenia and marked lymphocyte depletion of the spleen and lymph nodes (as seen in this patient), 'f-celi depletion, cutaneous anergy to recall antigens, impaired lymphocyte blastogenic response to mitogens and antigens, and thymic aplasia have been described. Clinical correlates of such altered cell-mediated immunity may be the development of life-threatening opportunistic infections: fatal cytomegalovirus infection [2], disseminated cutaneous verrucosis caused by human papillomavirus [3], and disseminated candidiasis [5] have been reported. To the best of our knowledge, this is the fourth reported case of P. carinii pneumonia in a patient with dyskeratosis congenita [2, 4, 7]. Three of the patients died as a direct consequence of their pulmonary infection, and delayed diagnosis of this potentially treatable condition obviously was common. Whereas it is uncertain whether corticosteroid treatment in our case may have contributed to the development of P. carinii pneumonia, we hypothesize that the incidence of this and other opportunistic infections may, independent of pretreatment with steroids, be much higher in dyskeratosis congenita than expected and previously recognized.
1057
Correspondence
References
I. Segreti J, Gootz TO, Goodman U, et al. High-level quinolone resistance in clinical isolates of Campylobacter jejuni. J Infect Dis 1992; 165:667-70. 2. Adler-Mosca H, Luthy-Hottenstein J, Lucchini GM, Burnens A, AltweggM. Development of resistance to quinolones in five patients with
Another Case of Pneumocystis carinii Pneumonia in a Patient with Dyskeratosis Congenita (Zinsser-Cole-Engman Syndrome)
campylobacteriosis treated with norftoxacin or ciproftoxacin. Eur J Clin Microbiol Infect Dis 1991;10:953-7. 3. Rautelin H, Renkonen OV, Kosunen TV. Emergence of ftuoroquinolone resistance in Campylobacter jejuni and Campylobacter coli in subjects from Finland. Antimicrob Agents Chemother 1991;35:2065-9. 4. Wistrom J, Jertborn M, Ekwall E, et al. Empiric treatment of acute diarrheal disease with norfloxacin. A randomized, placebo-controlled trial. Ann Intern Med 1992; 117:202-8.
treatment, and extensive culturing (including that for viruses) and serological testing failed to identify any other organism. Results ofa serological test for HIV were negative. While receiving ventilatory support, he developed rapid progressive pulmonary insufficiency with diffuse pulmonary infiltrates and severe hypoxemia. Repeated examination of bronchoalveolar lavage fluid for Pneumocystis organisms was not diagnostic until 24 hours before the patient died. Because of severe thrombocytopenia, transbronchial or open lung biopsies had not been performed. Autopsy revealed fibrinous pleuritis; focal areas with pulmonary hemorrhage; and abundant, intensely eosinophilic, foamy, honeycombed material that completely filled the interalveolar septa and was positive for the periodic acid-Schiff reaction. In Grocott-Gomori methenamine-silver nitrate stains, typical P. carinii cysts and trophozoites could be seen. No other organisms were identified in the lungs or in other organs. Further pertinent findings were lymphocyte depletion with a lack of lymph follicles in prominent paratracheal and paraaortic lymph nodes, a reduction of the white pulp of the spleen, and strikingly hypocellular bone marrow with near absence of megakaryocytes. Dyskeratosis congenita is a rare inherited disorder of which ,..., 100 cases have been described in the literature since the first report by Zinsser in 1906. Patients with the syndrome present with certain typical dermatologic features, ofwhich dystrophy or absence of the nails (figure I) and hyperkeratosis with areas of hypopigmentation and reticular hyperpigmentation become clinically prominent early in the course of the disease [2]. Many patients develop complications in the second and third decades
Correspondence: Dr. Winfried V. Kern, Medizinische Universitatsklinik und Poliklinik, Postfach 38 80, 0-7900 VIm, Germany. Clinical Infectious Diseases 1992;15:1056-7 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1506-0030$02.00
Figure 1. Complete loss of fingernails in a patient with dyskeratosis congenita.
Downloaded from http://cid.oxfordjournals.org/ at University of Exeter on August 1, 2015
SIR-Pneumocystis carinii pneumonia is a well-known lifethreatening complication of a variety of acquired or primary immunodeficiency disorders [1]. Outside the population of those infected with human immunodeficiency virus (HIV), the infection is most frequently diagnosed in children with acute lymphocytic leukemia and in organ or bone marrow-transplant recipients. We present the case of P. carinii pneumonia developing in a patient with dyskeratosis congenita (Zinsser-Cole-Engman syndrome), a rare multisystem disorder characterized by typical dermatologic lesions [2]. A 34-year-old man was admitted because of severe dyspnea, cachexia, and low-grade fever. At the age of 12 years, he was found to have dyskeratosis congenita. When he was 16 years old, mild thrombocytopenia was noted. He was well until a few years before admission, when he had complained of recurrent episodes of wheezing and unproductive cough and of weight loss. A limited diagnostic workup at that time revealed both restrictive and obstructive pulmonary abnormalities, and discrete bilateral reticular infiltrates were evident on chest radiographs. He was given intermittent medication including systemic steroids for presumed allergic asthma. On admission, the patient had bicytopenia and restrictive lung abnormalities with evidence of airflow obstruction. The chest radiograph showed bilateral reticular and nodular infiltrates including the lung base. Shortly after admission, the patient developed acute airway obstruction, with pneumomediastinum extending to the neck and parapharyngeal space, and a small pneumothorax. He refused any invasive diagnostic evaluation. Conservative treatment including repeated administration of steroids because of apparent airway obstruction eventually failed, and the patient was intubated. The subsequent hospital course was characterized by severe thrombocytopenia with spontaneous bleeding, mild neutropenia and lymphopenia, repeated extubation failures with tracheobronchitis, and excessive oropharyngeal inflammation due to Staphylococcus aureus. He was given adequate antibacterial
CID 1992; 15 (December)
CID 1992;15 (December)
Correspondence
Effects of Antimalarial Chemoprophylactic Agents on the Viability of the Ty21a Typhoid Vaccine Strain SIR-An increase in travel to the developing world has brought about a greater concern for the prevention of illnesses that may be acquired abroad. The attenuated Ty2la oral typhoid vaccine (Vivotif; Berna, Berne, Switzerland) is often recommended because its efficacy is comparable to that of the inactivated injectable vaccine and it is associated with a relative lack of adverse effects [I]. Because areas of the world where typhoid fever is endemic may coincide with areas where chloroquine-resistant Plasmodium falciparum malaria is endemic, pretravel recommendations for protection in these regions often call for weekly
This work was presented at the Annual Meeting of the American Society of Tropical Medicine and Hygiene held on 1-6 December 1991 in Boston. Mefloquine powder was provided by the Department of Medicinal Chemistry, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, D.C. Correspondence: Dr. Phyllis E. Kozarsky, Emory University School of Medicine, Emory Crawford Long Hospital. Division oflnfectious Diseases, 20 Linden Avenue, Atlanta, Georgia 30365. Clinical Infectious Diseases 1992;15:1057-8 © 1992 by The University of Chicago. All rights reserved. 1058-4838/92/1506-0031$02.00
Christian Rose and Winfried V. Kern Department ofPathology and Section ofInfectious Diseases, Ulm University Hospital and Medical Center, VIm, Germany
References I. Walzer PD, Kim CK, Cushion MT. Pneumocystis carinii. In: Walzer PD, Genta RM, eds. Parasitic infections in the compromised host. New York: Marcel Dekker, 1989:83-178. 2. Sirinavin C, Trowbridge AA. Dyskeratosis congenita: clinical features and genetic aspects. Report of a family and review of the literature. J Med Genet 1975; 12:339-55. 3. Bundino S, Zina AM, Bernengo MG. Dyskeratosis congenita with epidermodysplasia verruciformis of Lewandowsky and Lutz. Dermatologica 1978; 156: 15-23. 4. Wiedemann HP, McGuire J, Dwyer JM, et al. Progressive immune failure in dyskeratosis congenita. Report ofan adult in whom Pneumocystis carinii pneumonia and fatal disseminated candidiasis developed. Arch Intern Med 1984;144:397-9. 5. Giannetti A, Seidenari S. Deficit of cell-mediated immunity, chromosomal alterations and defective DNA repair in a case of dyskeratosis congenita. Dermatologica 1980; 160: 113-7. 6. Scoggins RB, Prescott KJ, Asher GH, Blaylock WK, Bright R W. Dyskeratosis congenita with Fanconi-type anemia: investigations ofimmunologic and other defects. Clin Res 1971; 19:409. 7. Kawaguuchi K, Sakamaki H, Onozawa Y, Koike M. Dyskeratosis congenita (Zinsser-Cole-Engman syndrome). An autopsy case presenting with rectal carcinoma, non-cirrhotic portal hypertension, and Pneumocystis carinii pneumonia. Virchows Archiv [AJ 1990;417:247-53.
administration of mefloquine beginning I week before travel in addition to administration of the typhoid vaccine [2]. The Ty2la vaccine strain requires active replication in the host gastrointestinal tract for development of immunity [3]. Unfortunately, there has been concern that some antimalarial agents may have antibacterial activity and thus may blunt the immune response if given concurrently with the oral typhoid vaccine [4, 5]. In fact, in vitro data have shown mefloquine to have activity against the cell membrane of some gram-negative organisms [6], and a more recent study of Ambrosch et al. [4] suggested that mefloquine taken 12 hours before the oral typhoid vaccine would interfere with serum antibody response to the vaccine. Although it is unknown whether serum antibody response to the vaccine correlates with protection, this response may be a marker; thus, interference is of concern. Because published data in this area are scant, recommendations concerning the timing of administration of the four everyother-day doses of typhoid vaccine and the start of weekly mefloquine prophylaxis vary. The current Vivotif package insert fails to address the potential problem. In recent discussions with the manufacturer, it was suggested that one wait only 18-24 hours after taking mefloquine before beginning the vaccine course (personal communication; S. Cryz, Swiss Serum and Vaccine Institute, Berne, Switzerland). On the other hand, the Enteric Diseases Branch of the Centers for Disease Control in
Downloaded from http://cid.oxfordjournals.org/ at University of Exeter on August 1, 2015
of their life. Mucosal leukoplakia and carcinoma have frequently been reported. Progressive bone marrow hypoplasia (usually beginning with thrombocytopenia) is another frequent complication. Infections ofdyskeratosis congenita, descriptions of which are often taken from the patients' histories and are therefore poor, have been attributed to leukopenia in some reports [2]. Recent data, however, suggest a rather complex immunodeficiency with severely impaired cellular immunity in patients with the syndrome [3-6]. Lymphopenia and marked lymphocyte depletion of the spleen and lymph nodes (as seen in this patient), 'f-celi depletion, cutaneous anergy to recall antigens, impaired lymphocyte blastogenic response to mitogens and antigens, and thymic aplasia have been described. Clinical correlates of such altered cell-mediated immunity may be the development of life-threatening opportunistic infections: fatal cytomegalovirus infection [2], disseminated cutaneous verrucosis caused by human papillomavirus [3], and disseminated candidiasis [5] have been reported. To the best of our knowledge, this is the fourth reported case of P. carinii pneumonia in a patient with dyskeratosis congenita [2, 4, 7]. Three of the patients died as a direct consequence of their pulmonary infection, and delayed diagnosis of this potentially treatable condition obviously was common. Whereas it is uncertain whether corticosteroid treatment in our case may have contributed to the development of P. carinii pneumonia, we hypothesize that the incidence of this and other opportunistic infections may, independent of pretreatment with steroids, be much higher in dyskeratosis congenita than expected and previously recognized.
1057
