Pneumocystis pneumonia REVIEW carinii pneumonia immunology pneumonia, alveolar interstitial plasma cell capillary block pentamidine isothionate Pneumocystis Carinii Pneumonitis A Review Departments of Pediatrics and Microbiology, University of Florida, Gainesville, Fla. 32601, USA Introduction In many instances, the desperate clinical condition of the affected individuals seems to have precluded The purpose of this essay is to organize the available those clinical studies necessary to understand the information about Pneumoqwtis carinii pneumonitis and distinctive and altered physiology of Pneumocystis ca- to rclatc the host factors and the pathophysiology with rinii pneumonitis. However, there are some reports, as the clinical disease. Since a successful chemotherapeu- well as unreported data available to the author, which tic approach has been rcported by several workers, correlate the pathological findings with the clinical and since the incidence of this disease seems to be in- picture of this disease. The review will try to emphasize creasing in a select group of patients, it is important these pathophysiologic features in order to present that the early ante nzortem diagnosis of this disease be those diagnostic hints which the physicians may readily established. The emphasis in this essay, therefore, will test. Rvcognition of these unusual clinical features be to relate the unique characteristics of the pathogen should aid early diagnosis of Pneumocystis carinii pneu- to the pathophysiological state characteristic of the monitis. pneumonitis induced by Pneumocystis carinii. It is hoped Of particular interest is the possibility that accurate that a logical analysis of the data with illustrative case analysis of the incidence of immunoglobulin deficien- material will permit a distinct clinical picture to cy syndromes in the general population may be in- emerge and to pose some new question about the pa- fluenced by Pneumocystis carinii infections. Statistics thogen and the unique host-parasite interaction which that project the incidence of immunoglobulin defi- may be subject to experimentation. ciency syndromes in the general population may dis- Several reviews have been extremely useful in the regard many cases of immunoglobulin deficiency dis- preparation of this manuscript and should be rrferred ease, especially hypogammaglobulinemic states of the to for a historical prospective as well as a morc com- congenital variety, which were previously classified as prehensive revirw of this literature [I-61. examples of the newborn human's unusual susceptibil- Pneunzo~ys/iscarinii pneumonitis is a disease induced ity to Pneunlocystis disease. The wide-spread use of more by an ubiquitous organism of low virulrnce and narrow precise diagnostic techniqurs for the immunoglobulin tissue spccificity in a susccptible host. In most instances, deficiency syndromes, as well as the increased atten- it is a latent infection which occurs in humans and tion of pathologists to this diagnosis, should reveal that animals at all stagrs of development. The distinction, many children with hypogammaglobulinemic states drawn by several workcrs, between the infantile and are afflicted with Pneumocystis carinii infection within adult form of the discasr may be due to the narrow age the first year of life. The difficulties in substantiating a range of patients obsrrvcd by individual authors. One diagnosis of hypogammaglobulinemia during this age aim of this review, therefore, will be to show that the period, however, must be appreciated. same host factors which permit infCction with Pneumo- cvstis carinii are operative in humans and animals of all ages. For instance, contagion, formerly thought to Case 2,figures IA-D be exclusively a feature of the infantile form of the disease has been shown to be an important factor in the E.T.F., an 8-year-old girl, was admitted to the Uni- transmission of thc disease to adults. vcrsity of Florida Teaching Hospital for the second Folds, Lisa Age. ll years Diognosis:Acquired Hypogammaglobulinemia ~~NUCOIL~CICD~~C~~SI~CELLULOSE ACETATE ELECTROPHORESIS Tolal Protein - 6.29gm.r Albumin . 3.77 01 . 0.33 n2 - 0. 84 6. 1.01 7 . 0.13 SERUM IMMUNOGLOBllLlN LEVELS CLINICAL SYMPTOMS: Irohemrgglutlnins: BlooO lypP A Anti-8 - 0 Freouent baclerial pneumonia chrbn~c011tir media wilh hearing deficlf Anli.d,pnther,a 0. 0015 ~.ii.iml. Pneumocyrlis C-I pneumon~llr bone marrow plasma cellr. OllDOO Fig.1. A. Laboratory data. B. X-ray, acute phase of Thc vital capacity as determined with a Collins vitalo- disease. C. Onc month post pentamidine therapy. meter was 0.7 liter (normal 2.0 liter). X-ray study D. Three years post therapy. revealed minimal pulmonary scarring without evid- ence of acute disease. An appropriate work-up was con- time on July 31, 1964, with the chiefcomplaint offever sistent with a diagnosis of hypogammaglobulinemia. and dry cough, associated with increasing respiratory Treatmrnt was started with intramuscular injec- difficulty. The patient had had recurrent respiratory tions of pooled commercial Cohn fraction 11, 0.6 ml infections during her entirr life. Numerous bouts of per kilogram of body weight every month. She re- otitis media had necessitated multiple myringotomies. mained in relatively good health until 4 weeks before Severe attacks of bronchitis, with several episodes of admission, when a dry cough developed. Two weeks pnrumonia, were succcssfully treatcd with antibiotics. later she bccamr slightly febrile, with lethargy and Pneutnocystis carinii pneumonitis 133 Motz, Scott R. Age:3'/2 months ~iagnosis:~~~~~'~- hypogornrnoglobulinemto IMhlUNOELECTROPHORESIS CELL1II.OSE ACETATE ELtClROPHOHISl5 ff A*& Total Protein . 2. Iiqm.?. Atburntn . 1.34 a1 . 0. 14 02 ' 0.10 &an R rn P . o. 19 1 . 0.09 SERUM IMMUNOGLOBULIN LEVELS I A decreased appetite. Thr cough rcmaincd nonproduc- After one week of therapy definite clinical improve- tive, and there was no improvemrnt in thc clinical ment was observed. Decreased respiratory embarrass- condition dcspitc. tetracycline therapy. X-ray study of ment, as indicated by gradual diminution in cyanosis, the chest on the day of admission revealed diffuse bi- less dcpendcncy upon oxygen and a rcturn of appetite, lateral infiltrates most prominent at the hilar regions. was noticed during the 1st wcrk of thcrapy. Roentgeno- Physical examination showed a thin, chronically ill graphic evidence of improvement was detectable 3 girl in no acutc distress. Diminished chest expansion, weeks after treatment was started. Bone-marrow aspi- decreased breath sounds and hyporesonant percussion rations before therapy and on the 7th, 1 lth, and 14th were noted in the lung fields bilaterally. No advcnti- days of therapy showed the gradual de\~elopmcntof tious sounds werr heard, and clubbing was not present. crythroid hyperplasia (mycloid-erythroid ratio of 1 : 2), The temperature was 101.5"F (38.6"C), the pulse with marked megaloblastic changes. Occasional hyper- 130, and the rrspirations 44. The blood pressure was segmrnted ncutrophils and macroovalocytes wrre seen 95175. in the pcriphcral blood. Thr white-cell count was 2 1,000, with 87",, neutro- Clinical improvcment continued, and the patient phils, 6",, band forms, 3O,, eosinophils, 2 ",lymphocytes was discharged on the 48th hospital day with routine and 2 % monocytes. The hematorrit was 37",,; the rcd therapy of pooled gamma globulin at monthly intcr- cells and platelrts had normalmorphology. Urinalysis vals. Bone-marrow aspiration done the day before dis- was ncgative. Multiple cultures revcalcd no pathogcns. charge was within normal limits. One month later she Fungi and P. mrinii, sought with specific stains, were exhibitcd littlc respiratory embarrassment, with a not demonstratcd. High doses of penicillin, kanamycin weight gain of 2 kg, and was maintaining a full pro- and oxacillin wcre administerrd, but the patient's con- gram of activity without difficulty. The vital caparity dition deteriorated over the next 7 days. Breathing was 0.8 liter (normal, 2.0 liter) at that time, not signifi- became laborrd and shallow; thc respirations rose to cantly di!Yercnt from that obtained at a clinic visit 80. Attcmpts at removal from a moist oxygen-enriched before this episode (0.7 liter). environmrnt provoked severe cyanosis. Thoracotomy Continued sino-pulmonary infections have persisted under light gencral anesthrsia was performed to obtain despite antibiotic thcrapy. Her \pita1 capacity has risen a lung biopsy. A rrlatively avascular, yellowish, stiff to 1.5 liters. Currently, she enjoys a full range of activ- pulmonary parenchyma was noted. The pleural sur- ity. faces were grossly normal. The biopsy specimen ob- tained was characteristic in appearance for Pr~~u~troryslis cariuii pncumonitis. Immediately after the diagnosis Ca~e2,,Jigure~ PA arid B was established by means of the frozen section, hydro- xystilbamidine, 4 mg per kilogram of body weight, This four month old male was brought to the hospital was injected intravenously each day. Three days later with a chirfcomplaint of increasing respiratory distress, this was replaced by therapy with pentamidine iso- cyanosis, fever, and weight loss. Following a normal thionate, 4 mg per kilogram intramuscularly, which gestation and normal delivery, this infant developed was then given for 14 days. During this period, all other frequent severe upper rrspiratory infections until the chemotherapy was discontinued. age of threc and a half months. These wrrr succcssfi~lly treated with antibiotics.