Desquamative Interstitial Pneumonia Associated with Granulomatous Lymphadenopathy

Desquamative Interstitial Pneumonia Associated with Granulomatous Lymphadenopathy* Basil vlogopoulo8, M.D.;oO Hoon T. Chung, M.D.;t

Francis M. Fitzmaurice, M.D.;:!: ]. Clayton CampbeU, M.D., F.C.C.P.;§ and Guillermo V. Villacorte, M.D.II

A unique association between desquamative intentitial pneumonia and granulomatous Iympbadenopathy in a u-year-old black girl is presented. Although clinical and laboratory improvement foDowed corticosteroid therapy, fairly severe restrictive pnlmooary disease persisted.

I

n 1965, Liebow et all first defined desquamative interstitial pneumonia as an entity distinct from other types of chronic interstitial pneumonia. Scadding, 2 on the other hand, believes that desquamative interstitial pneumonia is no more than an early stage of the classic or usuaI interstitial pneumonia. Desquamative interstitial pneumonia is rare in children, with only 13 cases reported in the Iiterature. 8 - 10 The present case has the unusuaI feature of granulomatous lymphadenopathy.

CASE

REPoRT

A six-year-old blaclc girl was hospitalized because of tachypnea. dyspnea on exertion, and anorexia of one month's duration. Born prematurely (weight at birth, 2,340 gm [5 Ib 21' ozJ>, she had developed mild respiratory distress which lasted for two days. At the age of one month, the patient had been hospitalized for bronchopneumonia. Growth and development had been within normal limits. The patient had lived in Omaha all of her life and had just moved to a pigeon-inhabited house two months before the current admission to the hospital There had been no history of exposure to noxious agents. There was no family history of

similar disease.

The patient's respiratory rate was l00/min, the pulse rate was 164 beats per minute, the blood pressure was 88/68

mm Hg, and her temperature was 39·C (102.2°'F). Her height was III em (3 ft 8 in; 25th percentile), and her weight was 16.3 kg (36 Ib; third percentile). The patient had facial edema, and her cervical veins were distended. Both lungs were clear to percussion and auscuItation. Strong pulsations were felt over most of the precordium. The point of maximal impulse was at the fourth intercostal space, 2 em lateral to the left sternal border. The pulmonic second sound was louder than the aortic second sound. No murmur was heard, but there was a gallop rhythm with a third heart sound. A firm and tender liver was palpable 6 em below the right costal margin. Moderate digitial clubbing and cyanosis were noted, and there were a few pea-sized lymph nodes in the neck and inguinal regions. The findings from neurologic examination were normal. °From the Departments of Pediatrics, Pathology and Internal Medicine, Creighton University School 01 Medicine, Omaha. ° °Pediatric Resident. ASSistant Professor of Pathology. Professor of Pediatrics. Assistant Professor of Internal Medicine. Assistant Professor of Pediatrics.

~

780 YWOPOULOS ET AL

FIGURE

1. Chest x-ray film taken on admission.

Chest x-ray films disclosed generalized cardiomegaly, with widening of the superior mediastinum but no parenchymal disease (Fig 1). An electrocardiogram revealed sinus tachycardia, incomplete right bundIe-branch block, and abnormal right axis deviation (110·). The arterial oxygen pressure was 31 mm Hg, and the oxygen saturation was 62 percent, rising to 450 mm Hg and 99 percent, respectively, when the patient was given oxygen (10 L/min). The arterial carbon dioXide tension and pH were normal. The results of laboratory studies were as follQws: hemoglobin level, 14.2 gm/l00 ml; hematocrit reading, 46 percent; and total white blood cell count, 12,700/cu mm, with 50 percent polymorphonuclear neutrophils, 9 percent band cells, 38 percent Iymphoeytes, and 1 percent each of monoCYtes, eosinophils, and basophils. The findings from the following studies were normal: blood chemistry; urinalysis; smears and cultures of blood, bone marrow, lymph node, lung, urine, and sputum; lupus erythematosus preparation; antinuclear antibody tests; slide test for infectious mononucleosis (MONOSPOT); and febrile and cold agglutinin titers. The total serum level of protein was 8.5 gm/l00 ml, with a 'Y-globulin level of 2.8 gm/l00 ml (normal, 0.74 to 1.70 gm/l00 ml). Serum levels of immunoglobulins were as follows: IgG, 2,000 mg/l00 ml (normal, 650 to 1,200 mg/IOO ml); 19A, 265 mg/IOO ml (normal, 50 to 175 mg/l00 ml); and IgM, ISO mg/IOO ml (normal, 40 to 121 mg/l00 ml). The following titers were determined: anti-A antibody, 1:16; anti-B antibody, 1:64; antistreptolysin, 125 Todd units; latex rheumatoid factor, 1:20; and direct Coombs' test, 1:20, becoming negative three weeks later. Reactions on immunologic tests for coccidioidomycosis, histoplasmOliis, blastomycosis, toxoplasmosis, cytomegalovirus, and herpes virus were negative. The precipitin test for hypersensitivity pneumonitis was positive only for Aspergillus. Cutaneous tests with purified protein derivative of tuberculin, histoplasmin, and Aspergillus were negative. Leukoeytic, complementmediated, and cell-mediated immune functions were normal. Upon admission, the patient was placed under the oxygen tent, and digitalis was administered. Although she survived heart failure, her improvement was only slight and very in-

CHEST, 72: 6, DECEMBER, 1977

The patient was discharged after two months and was fonowed-up in the outpatient clinic, where her dosage of prednisone was gradually tapered to 10 mg every other day. Isoniazid and rifampin were discontinued after one year. Two years after her hospitalization, the patient appeared to be well clinically. Her disease had apparently been arrested, but not reversed, by steroid therapy.' Studies of pulmonary function and diffusion, which heretofore were impossible to perform, revealed a marked restrictive defect with alveolocapillary block. Minimal digital clubbing remained. DISCUSSION

•

•

FIGURE 2. Section of lung biopsy, showing thickened and 6brotic septa infiltrated with lymphocytes and plasma cells. Desquamated PAS-positive granular pneumocytes are seen in alveolar spaces (hematoxylin-eosin, original magnification X 450).

sidious. On the fifth day of hospitalization, the patient's temperature began to spike to 40°C (104°F). Her erythrocyte sedimentation rate, which had been 7 mm/br on admission, went up to 40 mm/br and later on to 73 mm/br. The findings from cardiac catheterization performed on the 13th day of hospitalization were unremarkable, except for pwmonary hypertension of 60 mm Hg systolic. The bone marrow showed nonspecific reactive eosinophilia and plasmacytosis. Biopsies of the right inguinal, superior mediastinal, and right axillary lymph nodes were obtained on the 16th, 18th, and 25th days of hospitalization, respectively (Fig 2). An open lung biOpsy performed on the 25th day of hospitalization showed histopathologic features of desquamative interstitial pneumonia (Fig 3). Once the diagnosis had been established, treatment with prednisone, isoniazid, and rifampin (rifampicin) was initiated. Dramatic subjective and objective improvements were observed, as evidenced by defervescence, disappearance of respiratory difficulty, improved appetite, and normalization of the patient's blood gas levels, sedimentation rate, immunoglobulin levels, rheumatoid factor test, and chest x-ray film.

FIGURE 3. Representative area of biopsy of mediastinal lymph node, showing noncaseating granuloma characterized by diffuse proliferation of histiocytes and epithelial cells with occasional Langerbans' cells. Moderate numbers of plasma cells and eosinophils are present in SU;1usoids. Similar finciingll were seen in other nodes (hematoxylin-eosin, original magnification X 1(0).

CHEST, 72: 6, DECEMBER, 1977

The clinical picture of desquamative interstitial pneumonia in children is similar to that observed in adults, eg, insidious onset with tachypnea. cyanosis, and tachycardia. Fever is low-grade in character and seldom exceeds 38°C (100.4°F). Older children tend to develop anorexia. lose weight. and complain of easy fatigability. Physical examination is usually unrevealing. The chest x-ray 6lm may show inegularly distributed shadows, rather than the basal ground-glass consolidation seen in adults. Mild leukocytosis is occasionally seen. Diagnosis is made by lung biopsy. Except in infants, in whom the prognosis appears to be very Poor, the response to steroid therapy is usually good and dramatic. The presence of granulomata in the mediastinal and peripheral lymph nodes but not in the lung, as seen in our patient, had not been reported previously. a-lO This feature, together with the hyperimmunoglobulinemia, elevated erythrocytic sedimentation rate, and hyperthermia. was suggestive of systemic infection; however, the existence of such systemic infection and its relationship to the pulmonary pathologic findings could not be ascertained. Hypergammaglobulinemia as Stich is more likely to be associated with either usual or lymphoid interstitial pneumonia. 8 In only one case of desquamative interstitial pneumonia was an elevated serom concentration of immunoglobin observed. 7 The noncaseating nature of the granuloma, negative cultures for acid-fast bacilli, and negative tuberculin test, despite intact cellular immune response, made the diagnosis of tuberculosis unlikely; however, a 12-month course of combined therapy with rifampin and isoniazid was deemed justi6able. Tuberculosis preceding desquamative interstitial pneumonia had recently been reported. 4 Although the possible etiologic role of fungi had been virtually ruled out, the same could not be said for viruses. Facilities for viral cultures and electron microscopic studies were not available at the time when the biopsies were done. A few cases of desquamative interstitial pneumonia have been ushered in by inlIuenzalike symptoms, thus suggesting the possibility of a viral etiology; 8,10 however, efforts to document the presence of a virus failed. 1l • 12 Because of the history of proximity to pigeons, pigeon breeder's disease and psittacosis had to be taken into consideration in our patient. Factors arguing against the former etiology are the actual progression of the disease in the environment of the hospital and the absence of specific antibody for either pigeon's serum or droppings. Although there is some similarity between the histopathologic pictures of desquamative interstitial pneumonia and psittacosis, the latter tends

DIP ASSOCIATED WITH GRANULOMATOUS LYllPHADENOPAm 781

to have a more acute clinical course, with sudden onset of fever, myalgia, photophobia, and chills. The absence of involvement of multiple systems of the body virtually negates the possibility of sarcoidosis and systemic lupus erythematosus. Thus, although the cause of and the relationship between the granulomatous lymphadenopathy and desquamative interstitial pneumonia could not be established, this case nevertheless illustrates the possibility of varied etiologic factors in the latter condition. It would appear that while clinical and laboratory improvements, as well as the resolution of the mediaStinal and peripheral lymphadenopathy, had been brought about by steroid therapy, a considerable resbictive pulmonary disease persisted. The distinction between desquamative interstitial pneumonia and other interstitial pneumonias has, therefore, remained controversial The need for an aggressive approach to establish the diagnosis and identify the etiologic factor (s) early in order to initiate appropriate and more specific treabnent cannot be overemphasized. ACKNOWLEDGMENT: We wish to express our sincere M.~.J and Arthur S. appreciation to Averill A. Lie~l Patehe~, M.D., for reviewing me pathologic materials rendered by presented in this 1'ej)Ort. The inv81uable advi~ Frank M. Shepard, M.D., Chairman of the Deparbnent of Pediatrics, and by Robert G. Townley, M.D.,.anCi AHred Brody, M.D. of the ;Department of InterDal Me<11cine is also hereby gratefully acIcnOwledged.

REFERENCES

1 Liebow AA, Steer A, Billingsley JG: Desquamative interstitial pneumonia. Am J Moo 39:369-404, 1965 2 Scadding JG: Lung biopsy in the diagnosis of diHtue lung disease. Br Med J 2:551-564, 1970 3 Schneider RM, Nevius DB, Brown HZ: Desquamative intentitial pneumonia in a four year old child. N Eng! J Med 277:1056-1058, 1967 4 Wipf R: Pneumonpathic interstitielle desquamative chez un ecolier nord-africain vraisemblablement associ~ a une tuberculose

5 6

7 8 9 10 11 12

pulmonaire.

Schweiz

Med

Wochenschr

100:1845-1846, 1970 Buchta RM, Park S, Giammona ST: Desquamative interstitial pneumonia in a 7 week old infant. Am J Dis Child 120:341~, 1970 Liebow AA, cited in Kendig EL Jr (-eel): Disorders of the Respiratory Tract in Children: Desquamative Interstitial Pneumonia in Pulmonary Disorders (vol 1). Philadelphia, WB Saunders Co, 1972, pp 325-331 Howatt WF, Heidelberger KP, LeGlovan DP, et al: Desquamative interstitial pneumonia: Case report of an infant unresponsive to treatment. Am J Dis Child 126:346, 1973 Barnes SE, Godfrey S, Millward-Sadler GH, et al: Desquamative fibrosing alveolitis unrespQusive to steroid or cytotoxic therapy. Arch Dis Child 501:324-327, 1915 Gaensler EA, Goff AM, Prowse CM: Desquamative interstitial pneumonia. N Engl J Med 274:113-123, 1966 Bates DV, Macklem PT, Christie RV: Respiratory Function in Disease. Philadelphia, WB Saunders Co, 1971, p272 Patchefsky AS, Banner M, Freundlich 1M: Desquamative interstitial pneumonia: Significance of intranuclear virallike inclusion bodies. Ann Intern Med 74:322-327, 1971 McNary WF, Gaensler EA: Intranuclear inclusion bodies in desquamative interstitial pneumonia: Electron microscopic observations. Ann Intern 74:404-407, 1971

Moo

782 DE SOUZA,

upsm, SPAGNOLO

Mediastinal Compression due to Tension Hydrothorax* Romaldo DeSouza, M.D.;oO Nathan Lipsett, M.D.;oO and Samuel V. Spagnolo, M.D.f We desatbe a p8tieat in whom a malignant pleural effusion accumulated witb _cient pressure to cause mediastinal compression resultiDg in acute respiratory distress, dysp""'" and ......ve edema of the lower RtremitJes. Emeraeaey thoracocentesis produced 1Dunediate reBel 01 respiratory symptoms and dyspbagi8, with gradual disappeanmce of the edema and a weiPt I0Il of 6.8 kg (15 Ib) without adjuDdlve medications. It II ..... gested that thoracocentesis Is a life-saving Dle8lllre iD this clrc1llD8taDce and should be done lDunediately In patients with sImD8r Initial dbdcaI fiDdiDp, • further diapostIc evaluation or other therapy directed to the mediasflnum wiD not reUeve the tellSlon and wID oDly delay removal of the fluid.

is well known that massive pleural effusion can proI tduce respiratory distress and shift of mediastinal

strnctures; however, rarely does pleural effusion accumulate in large enough quantities to produce severe compression of the mediastinum. Management of mediastinal syndromes is often complex;1,2 however, when tension hydrothorax is responsible, simple emergency thoracocentesis is the treatment of choice and can be lifesaving. Since tension hydrothorax is rare, it especially may not be appreciated in patients with underlying malignant neoplasms. A patient successfully treated for tension hydrothorax is the basis for thiS report. CASEREroRT

A 46-year-old man was admitted to the hospital with a three-week history of dyspnea on exertion and a feeling of congestion in the chest. Chest x-ray SIms revealed complete opacification of the right hemithorax. At thoracocentesis, the fluid was an exudate. Pleural biopsy revealed infUtrating adenocarcinoma. The patient declined antineoplastic chemotherapy, was discharged, and returned to work. Following discharge, the patient required frequent thoracocentesis for relief of dyspnea. Four months after diagnosis, he was readmitted with a one-week history of increasing dyspnea, dysphagia, and swelling of his feet. Physical examination revealed an orthopneic, diaphoretic anxious-appearing man. His pulse rate was 115 beats per minute, and the respiratory rate was 24/min, with shallow respirations. The blood pressure was 110/SO mID Hg, with a paradoxical pulse of 20 mm Hg. The jugular veins were distended to the angle of the jaw. There was a hepatojugular reflUL The trachea was shifted to the left of the sternal notch. There was dullness to percussion throughout the right hemithorax, with absent breath sounds and absent vocal fremitus. Heart murmurs or gallop rhythms with third or fourth heart sounds were not o From

the Pulmonary Disease Section, the Medical Service, Veterans Administration Hospital, Washington, DC. o °Pulmonary Fellows, Pulmonary Disease Section. tChief,. Pulmonary Disease Section, and Associate Professor of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC. Reprint requesta: Dr. DeSouza, V A Hospital, 50 Irving Street, NW, Waahlngtoo, DC 20422

CHEST, 72: 6, DECEMBER, 1977