Talc Granulomatosis

pregnancy.12 In these cases, the patients’ monitoring should be very cautious, with repeated ultrasonographic examinations and plasma hormonal determinations. Their results could argue for a rapid withdrawal of HCG and a recommendation to avoid any exposure to pregnancy. At least one, if not all, of these signs were present in our patients. The severity of OHSS varies with the delay between the onset of symptoms and the stimulation: within 3 to 7 days of HCG administration, it is often moderate to severe, while a later onset (12 to 17 days) often signals a more severe clinical form. It generally spontaneously resolves in 7 days in the absence of pregnancy, but may last 10 to 20 days otherwise. In any case, the treatment of minor forms of OHSS includes abundant salt intake. In moderate forms, such as those reported herein, thoracentesis might be indicated. In conclusion, the frequency of OHSS presenting with an isolated pleural effusion is probably underestimated in the literature due to its usually spontaneously favorable outcome. The clinical context can be particularly misleading for pulmonary embolism. This syndrome is neither mentioned in general reviews dealing with the etiologies of pleural effusions13 nor in those regarding drug-induced lung diseases.14,15 However, chest physicians should be more aware of this syndrome, in order to ensure a better and minimally invasive management of these potentially pregnant patients.

References 1 Golan A, Ron-El R, Herman A, et al. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv 1989; 44:430 – 440 2 Delvigne A, Demoulin A, Smitz J, et al. The ovarian hyperstimulation syndrome in in-vitro fertilization: a Belgian multicentric study; clinical and biological features. Hum Reprod 1993; 8:1353–1360 3 Elchalal U, Schenker J. The pathophysiology of ovarian hyperstimulation syndrome: views and ideas. Hum Reprod 1997; 12:1129 –1137 4 Navot D, Bergh PA, Laufer N. Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. Fertil Steril 1992; 58:249 –261 5 Man A, Schwarz Y, Greif J. Pleural effusion as a presenting symptom of ovarian hyperstimulation syndrome. Eur Respir J 1997; 10:2425–2426 6 Caliandro R, Labalme MJ, Perol M, et al. Pleure´sie aigue¨ secondaire a` une hyperstimulation ovarienne apre`s fe´condation in vitro. Rev Mal Respir 1996; 13:68 –70 7 Wood N, Edozien L, Lieberman B. Symptomatic unilateral pleural effusion as a presentation of ovarian hyperstimulation syndrome. Hum Reprod 1998; 13:571–572 8 Friedler S, Rachstein A, Bukovsky I, et al. Unilateral hydrothorax as a sole and recurrent manifestation of ovarian hyperstimulation syndrome following in-vitro fertilization. Hum Reprod 1998; 13:859 – 861 9 Stewart JA, Hamilton PJ, Murdoch AP. Thromboembolic disease associated with ovarian stimulation and assisted conception techniques. Hum Reprod 1997; 12:2167–2173 10 Bergh PA, Navot D. Ovarian hyperstimulation syndrome: a review of pathophysiology. J Assist Reprod Genet 1992; 9:429 – 438 11 Loret de Mola JR, Arredondo-Soberon F, Randle CP, et al. Markedly elevated cytokines in pleural effusion during the 258

12

13 14

15

ovarian hyperstimulation syndrome: transudate or ascites? Fertil Steril 1997; 67:780 –782 Priou G. Les hyperstimulations ovariennes en PMA (Procre´ation Me´dicalement Assiste´e): quelle attitude pratique? Contracept Fertil Sex 1996; 24:647– 649 Sahn SA. The pleura: state of the art. Am Rev Respir Dis 1988; 138:184 –234 Cooper JA, White DA, Matthay RA. Drug-induced pulmonary disease: Part 2. Noncytotoxic drugs. Am Rev Respir Dis 1986; 133:488 –505 Foucher P, Biour M, Blayac JP, et al. Drugs that may injure the respiratory system. Eur Respir J 1997; 10:265–279

Talc Granulomatosis* A Differential Diagnosis of Interstitial Lung Disease in HIV Patients Daniel N. Nan, MD; Marta Ferna´ndez-Ayala, MD; Luis Iglesias, MD; Daniel Garcı´a-Palomo, MD; Jose A. Parra, MD; and M. Carmen Farin˜as, MD

Consumers of adulterated drugs may present with talc-induced interstitial lung disease. A transbronchial biopsy specimen showing granulomas with intracellular talc crystals is necessary to confirm this diagnosis. In patients infected with HIV, such a condition can be indistinguishable at first glance from opportunistic infections or other pulmonary diseases. A case is presented of a seropositive patient whose chest radiographs showed a diffuse interstitial pattern. (CHEST 2000; 118:258 –260) Key words: AIDS; interstitial lung disease; talc

pulmonary granulomatosis is an uncomT alc-induced mon disorder, reported especially among consumers of adulterated drugs or of pulverized tablets injected IV.1,2 In patients infected with HIV, it may be indistinguishable at first glance from opportunistic infections or from other pulmonary diseases. A case is presented of an HIVseropositive patient whose chest radiographs showed a diffuse interstitial pattern. *From the Infectious Diseases Unit, Department of Internal Medicine (Drs. Nan, Ferna´ndez-Ayala, Iglesias, Garcı´a-Palomo, and Farin˜as), Hospital Universitario Marque´s de Valdecilla, Universidad de Cantabria, Santander, Spain; and the Radiology Service (Dr. Parra), Hospital Sierrallana, Torrelavega, Spain. Manuscript received June 22, 1999; revision accepted December 15, 1999. Correspondence to: M. Carmen Farin˜as, MD, Infectious Diseases Unit, Department of Internal Medicine, Hospital Universitario Marque´s de Valdecilla, Avd Valdecilla, s/n, 39008 Santander, Spain; e-mail: [email protected] Selected Reports

Case Report A 38-year-old man, who smoked 20 cigarettes a day and had taken drugs IV until 1 month previously, was admitted to the hospital with progressive dyspnea on moderate exertion, dry cough, pleuritic pain in his right side, night sweats, and anorexia, with a 10-kg weight loss in the previous 5 months. Chest radiographs showed a bilateral interstitial pattern, and bronchoscopy with BAL was performed, with normal results. Given the patient’s history of drug addiction, he was tested for HIV and was found to be seropositive. The patient then discharged himself from the hospital before tests could be completed, but was readmitted 2 months later with the same symptoms. Physical examination findings were unremarkable. Tests showed slight normocytic anemia, first-hour erythrocyte sedimentation rate of 116 mm, lactate dehydrogenase of 840 IU/L, and hypoxemia of 72 mm Hg. Viral burden was 560,000 copies per milliliter, and CD4 lymphocyte count was 11 cells per microliter. An ECG showed right axis and right ventricular hypertrophy. Chest radiographs revealed the same bilateral alveolo-interstitial pattern observed previously, predominantly in the upper and midleft lung fields (Fig 1). Gallium lung scan showed intense diffuse bilateral uptake. Microbiological tests performed to rule out the typical opportunistic infections found in HIV patients were negative. Empirical treatment with cotrimoxazole produced no improvement in the clinical or radiologic picture. After the onset of a steady fever, another bronchoscopy with BAL and a transbronchial biopsy were done, and treatment with imipenem and ganciclovir was applied. However, the patient died suddenly the next day, 2 weeks after this second hospital admission. An autopsy was not performed. Histologic examination of the transbronchial biopsy specimen showed talc-induced granulomas (Fig 2). No organisms were seen in the tissue from the biopsy specimen, and BAL cultures were negative.

Figure 1. Chest radiograph showing a bilateral alveolo-interstitial pattern, predominantly in the upper and mid-left lung fields.

Figure 2. Pulmonary interstitium showing a talc particle (green) within a giant cell and another lying free in the interstitium (hematoxylin-eosin; original ⫻ 100).

Discussion Talc-induced pulmonary granulomatosis is a rare disorder with an unknown physiopathologic mechanism, although the most likely hypothesis for its origin is an immunologic mechanism of delayed hypersensitivity. It produces slowly progressive dyspnea on exertion (even after IV drug use has ceased), dry cough, nonspecific chest pain, and, occasionally, anorexia, weight loss, slight fever, and night sweats. Lung sounds are usually normal, or with minimal bibasal crepitations, and talc deposits may sometimes be visualized in the blood vessels of the retina.3 Respiratory function tests generally show a persistent slight-to-moderate hypoxemia and a reduction of carbon monoxide diffusion. Findings from chest radiographs and CT scans range from diffuse micronodular patterns to major loss of structure of the pulmonary parenchyma due to massive fibrosis.3 Gallium lung scans generally show diffuse bilateral uptake. BAL typically reveals lymphocytosis with a predominance of CD8 lymphocytes, and talc crystals can be seen occasionally.4 A definitive diagnosis is obtained by examination of transbronchial or open-lung biopsy specimens, which show macrophages with intracellular talc crystals. The disease may develop into pulmonary hypertension and fibrosis. Treatment with corticosteroids has been attempted, with improvement of clinical and respiratory functions, although there is a risk of relapse after cessation. In the case of our patient, failure to perform a pulmonary biopsy along with the bronchoscopy, conducted when he was first admitted to the hospital, led him to be given empirical treatment for Pneumocystis carinii. Given the high prevalence in Spain of IV drug use among HIV patients, it is reasonable to suppose that talc-induced granulomatosis is widely underreported. Moreover, differential diagnosis to exclude opportunistic infections is difficult, due to relatively similar clinical and laboratory presentations. Pneumocystis pneumonia, tuberculosis, cytomegalovirus pneumonitis, or even Legionella, Mycoplasma, or Chlamydia pneumoniae may be sugCHEST / 118 / 1 / JULY, 2000

259

gested; neoplasms must also be excluded, eg, Kaposi’s sarcoma, bronchoalveolar carcinoma, lymphatic tumor, or lymphoid neoplasms. The first group is of particular importance, as these diseases may require empirical treatments due to their rapid development and adverse prognoses. Some clinicians argue strongly that patients presenting with the symptoms and radiologic and arterial blood gas abnormalities typical of P carinii pneumonia should have the diagnosis confirmed by bronchoscopy.5,6 Others have suggested that such patients may be treated empirically, with bronchoscopy reserved for those who fail to respond to specific therapy or whose conditions deteriorate thereafter.5,7 In our case, in which the patient presented with hypoxia, high serum lactate dehydrogenase, a positive gallium scan, and chest radiographs typical of Pneumocystis pneumonia, the condition was misdiagnosed, even though a bronchoscopy with BAL was performed. This experience has led us to strongly advocate, if other diagnostic measures do not yield a definitive diagnosis, performing a biopsy when a bronchoscopy is done on similarly affected HIV-infected patients, unless there is any contraindication, such as thrombocytopenia. In addition, we believe that the possibility of talc granulomatosis (associated with an active cellular immunity), should be considered when dealing with seropositive patients having a history of drug abuse who present with diffuse interstitial pulmonary disease, even those with advanced disease and a nonfunctional cellular immunity. In these cases, an early bronchoscopy along with a biopsy should be considered, as the identification of talc-induced granulomatosis would avoid diagnostic errors and, consequently, unnecessary treatment.

ECG Changes in a 25-Year-Old Woman With Hypocalcemia Due to Hypoparathyroidism* Hypocalcemia Mimicking Acute Myocardial Infarction Gu¨nter Lehmann, MD; Isabel Deisenhofer, MD; Gjin Ndrepepa, MD; and Claus Schmitt, MD

The case of a 25-year-old woman presenting with chest pain, ECG changes, and laboratory findings suggestive of myocardial infarction is reported. Cardiac catheterization showed impaired left ventricular performance but otherwise normal coronary arteries. Laboratory analyses revealed primary hypoparathyroidism, and supplementation with calcium and vitamin D3 was initiated. There was subsequent improvement in laboratory findings as well as echocardiographically determined left ventricular performance. Thereafter, the patient remained asymptomatic. Apart from some persisting ECG repolarization disturbances, there was complete normalization of the initial changes. This case demonstrates a combination of clinical, blood biochemical, and ECG findings mimicking acute myocardial infarction. (CHEST 2000; 118:260 –262) Key words: ECG changes; hypocalcemia; hypoparathyroidism Abbreviations: CK ⫽ creatine kinase; FS ⫽ fractional shortening; LDH ⫽ lactate dehydrogenase

Case Report ACKNOWLEDGMENT: We thank Dr. Javier Gomez Roma´n from the Department of Pathology for provision of photographs.

References 1 Arnett EN, Battle WE, Russo JV, et al. Intravenous injection of talc-containing drugs intended for oral use: a cause of pulmonary granulomatosis and pulmonary hypertension. Am J Med 1976; 60:711–718 2 Radow SK, Nachamkin I, Morrow C, et al. Foreign body granulomatosis: clinical and immunologic findings. Am Rev Respir Dis 1983; 127:575–580 3 Pare´ JA, Fraser RG, Hogg JC, et al. Pulmonary ‘mainline’ granulomatosis: talcosis of intravenous methadone abuse. Medicine (Baltimore) 1979; 58:229 –239 4 Farber HW, Fairman RP, Glauser FL. Talc granulomatosis: laboratory findings similar to sarcoidosis. Am Rev Respir Dis 1982; 125:258 –261 5 Miller R. HIV-associated respiratory diseases. Lancet 1996; 348:307–312 6 Broaddus C, Dake MD, Stulbarg MS, et al. Bronchoalveolar lavage and transbronchial biopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome. Ann Intern Med 1985; 102:747–752 7 Miller RF, Millar AB, Weller IV, et al. Empirical treatment without bronchoscopy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Thorax 1989; 44:559 –564 260

25-year-old woman was admitted to a hospital beA cause of loss of consciousness, and clonic and tonic

seizures. One and one-half years prior to the current admission, the patient was found to have hypocalcemia (1.5 mmol/L; normal range, 2.2 to 2.65 mmol/L) coincidentally at the time of a cesarean section, but without further diagnostic or therapeutic workup. Other than episodes of nocturnal dyspnea 4 months earlier, the patient was asymptomatic. During the last few days before this admission, she complained of dull pain in the extremities. The serum calcium concentration was 0.85 mmol/L. On regaining consciousness, she developed chest pain that was not relieved by short-acting nitrates. On transfer to our service, the initial ECG was suggestive for acute or evolving myocardial infarction, with ST-segment elevation in leads I and aVL, and concurrent ST-segment depression in leads III, aVR, aVF, V1, and V3-V5 (Fig 1, top, A). In

*From the Deutsches Herzzentrum Mu¨nchen and I. Med. Klinik, Klinikum rechts der Isar der Technischen Universita¨t Mu¨nchen, Munich, Germany. Manuscript received August 17, 1999; revision accepted December 8, 1999. Correspondence to: Gu¨nter Lehmann, MD, Deutsches Herzzentrum Mu¨nchen, Lazarettstra␤e 36, D - 80636 Mu¨nchen, Germany; e-mail: [email protected] Selected Reports