Correspondence
and actively motile flagellated amoebae. These were translucent oval 25–35 lm with pseudopodia and a polar tuft of flagellae lashing rhythmically 15 times/10 sec (Figure). Methylene blue staining differentiated microorganisms from ciliated bronchial cells. A definite history of contact with cockroaches was admitted by our patient, who denied travel outside India. The parasite was identified as Lophomonas blattarum, and oral metronidazole 400 mg thrice daily was initiated; steady improvement was noted, with absence of protozoa from BAL after one month of therapy. Anti-tuberculosis treatment was continued for 9 months and the patient attained clinical cure. Lophomonas is classified under supergroup Excavata, rank Parabasalia. Trophozoites encyst in adverse conditions and excyst in two motile forms under proper conditions. Given suitable temperature, humidity and oxygen concentration in the human respiratory tract, excysted trophozoites affect protease receptors and interact with tight-junctions.2 The pyriform trophozoite is 20–60 3 12–20 lm in size and bears a polar tuft of flagellae, the body being unstriated in L. blattarum. A trumpet-shaped calyx extends down the central axis and has a nucleus inside. A specialised cytoplasmic collar, the parabasal body, with numerous radiating tubules that support the nucleus-endomembrane system and axial filament, are seen on electron microscopy. This endomembrane assembly probably synthesises enzymes, lysosomes and peroxisomes.2 Various authors have distinguished cells from protozoans by absence of red granules, positivity to ultraviolet light or staining with Heidenham iron hematoxylin, Papanicolaou or Wheatley’s trichome.2,3 We used methylene blue stain and differentiated ciliated bronchial epithelial cells by perceiving motility of trophozoites on rigorous screening of wet mounts within 2 h of sample collection. A segment of alveolar membrane illustrated bronchial cells with static cilia and an embedded trophozoite with motile flagellae. Treatment consists of oral metronidazole 500 mg 8–12 hourly or 2 g daily in adults and 7.5–15 mg/kg every 8 h in children for a week. Severe cases may be treated with intravenous metronidazole 15 mg/kg/h followed by 7.5 mg/kg/6 h as maintenance.1,2,4,5 SANTWANA VERMA, MD* GHANSHYAM VERMA, MD† DIG VIJAY SINGH, MD* JITENDER MOKTA, MD‡ RAMESHWAR SINGH NEGI, MD§ ANUPAMA JHOBTA, MD¶ ANIL KANGA, MD* *Department of Microbiology, †Department of Dermatology ‡Dept. of Internal Medicine §Dept. of Pulmonary Medicine ¶ Department of Radiodiagnosis
369
Figure Translucent, oval to pear-shaped amoeboflagellate, 25–35 lm in size, with pseudopodia and a polar tuft of flagellae seen as a crown. Crenated red blood cells and necrotic material visible (magnification x 400).
Indira Gandhi Medical College Shimla, India e-mail: [email protected] http://dx.doi.org/10.5588/ijtld.14.0513 Conflict of interest: none declared.
References 1 Martinez-Giron R, Esteban J G, Ribas A, Doganci L. Protozoa in respiratory pathology: a review. Eur Respir J 2008; 32: 1354– 1370. 2 Martinez-Giron R, Van Woerden H C. Lophomonas blattarum and bronchopulmonary disease. J Med Microbiol 2013; 63: 1641–1648. 3 Ribas A, Mosquera J A. Amoeboflagellates in bronchial asthma. Acta Cytol 1998; 42: 685–690. 4 Ribas A, Martinez-Giron R, Ponte-Mittelbrum C, AlonsoCuervo R, Iglesias-Llaca F. Immunosuppression, flagellated protozoa in the human airways and metronidazole: observations on the state of the art. [Letter]. Eur Soc Organ Transplantation 2007; 20: 811–812. 5 He Q, Chen X, Lin B, Qu L, Wu J, Chen J. Late onset pulmonary Lophomonas blattarum infection in renal transplantation: a report of two cases. Intern Med 2011; 50: 1039–1043.
Cavitary tuberculosis and tracheal stenosis simulating granulomatosis with polyangiitis We describe a 38-year-old female who presented tracheal stenosis with lung cavities, illustrating the challenges of diagnostic differentiation between tuberculosis (TB) and granulomatosis with polyangiitis (GPA). The patient’s condition began with productive cough on May 2009, leading to progressive dysphonia. Initial acid-fast bacilli (AFB) test was negative. Biopsy of the larynx showed granulomatous laryngitis. In September, the patient’s symptoms had progressed to include dyspnoea, haemoptysis, fever and
370
The International Journal of Tuberculosis and Lung Disease
5 kg weight loss. On examination at our institution, in December 2009, she was 45 kg in weight, dyspnoeic and normotense with physical signs of left apical cavitary disease; the remainder of the examinations were normal. Chest X-rays are shown in the Figure. High-resolution lung computed tomography (CT) showed bilateral apical bullae, inferior right lobe segmentary consolidation and bilateral nodules, 5 mm in diameter (not shown). Blood cell count, urinalysis and blood chemistry were normal, and AFB sputum smear was again negative; erythrocyte sedimentation rate (ESR) was 38 mm/h, C-reactive protein (CRP) was 5.27 mg/l. Spirometry showed severe airflow obstruction, with forced vital capacity (FVC) 47%, forced expiratory volume at 1 second (FEV1) 39%, and FEV1/FVC 67%. Bronchoscopy showed irregular, winding trachea. The biopsy showed mucosal ulcers and chronic granulomatous inflammation. As GPA was suspected, antineutrophil cytoplasmic autoantibody (ANCA) tests were performed. Indirect immunofluorescence (IIF) tests were negative, as were PR3-ANCA and MPO-ANCA (ELISA). Lung biopsy was initially compatible with GPA, but the presence of scarce AFB led to treatment for TB and, a week later, prednisone at intermediate dose (25 mg daily), low-dose methotrexate (12.5 mg/week) and folate 5 mg daily were prescribed for GPA while awaiting the final results of culture. Culture was positive for pan-susceptible Mycobacterium tuberculosis a month later. Careful review of the biopsy concluded that TB was responsible for the clinical picture, and prednisone and methotrexate were rapidly withdrawn. The patient completed standard four-drug anti-tuberculosis treatment in accordance with Mexican standards (isoniazid 300 mg, rifampicin 600 mg, pyrazinamide 1.5 g, ethambutol 1200 mg daily for 2 months, followed by isoniazid 800 mg and rifampicin 600 mg thrice weekly for 20 weeks). The patient experienced full recovery, with negative AFB stains on follow-up, ESR 11 mm/h, CRP 0.17 mg/l and normal liver function tests. In April 2012 the patient had mild dyspnoea, with lung function tests showing severe airflow obstruction with no changes since those performed on admission. Oxymetry was 93%. She gave birth to a normal child, without complications. The lung manifestations of TB and GPA may be indistinguishable, with reports of ANCA positivity in TB, particularly in high-prevalence countries. Their titres, however, are usually low: on IIF less than one third of cases are PR3-ANCA positive.1,2 Although the presence of granulomas and vasculitis was suggestive of GPA, the latter was only found in the sites of caseous necrosis and in blood vessels adjacent to the location of the tubercle bacilli. TB is an occasional cause of infectious vasculitis.3 In GPA, subglottic, and sometimes tracheal, stenosis is characteristic, as opposed to what is observed in TB.4 There are probably no more than 400 reported cases, which contrasts with the high prevalence of
Figure Multiple dispersed nodules are seen in both lung fields. An irregular trachea can be seen, and in at least two levels through its course, stenosis can be seen.
disease worldwide. In our centre, a national reference institution for TB, this case seems to be the first. After treatment for TB the patient’s general and pulmonary condition recovered, although she still needs correction of the tracheal stenosis. In conclusion, the differential diagnosis of GPA must take all elements into account, including histopathological, and be adequately weighted in an individual context. In this case, despite the tracheal stenosis, lung cavities and vasculitis on lung biopsy, ANCA was negative. Treating this patient for GPA could have proved fatal. LUIS FELIPE FLORES-SUA´REZ* ´ SALDARRIAGA RIVERA* LINA MARIA ´ RIVERA ROSALES† ROSA MARIA NATLLELY RUIZ* ˜ ‡ RENATA BA´EZ SALDANA *Primary Systemic Vasculitides Clinic †Department of Pathology and ‡Third Clinical Service Instituto Nacional de Enfermedades Respiratorias Tlalpan, Mexico City, Mexico e-mail: [email protected] http://dx.doi.org/10.5588/ijtld.14.0633 Conflicts of interest: none declared.
References 1 Flores-Sua´rez L F, Cabiedes J, Villa A R, van der Woude F J, Alcocer-Varela J. Prevalence of antineutrophil cytoplasmic autoantibodies in patients with tuberculosis. Rheumatology 2003; 42: 223–229. 2 Pradhan V D, Badakere S S, Ghosh K, Pawar A R. Spectrum of anti-neutrophil cytoplasmic antibodies in patients with pulmonary tuberculosis overlaps with that of Wegener’s granulomatosis. Indian J Med Sci 2004; 58: 283–288. 3 Gordon C, Luqmani R, Fields P, Howie A J, Emery P. Two cases of Wegener’s tuberculosis. Br J Rheumatol 1993; 32: 143–149. 4 Smati B, Sadok M, Ayadi A, et al. Tuberculosis of the trachea. Ann Thoracic Surg 2006; 82: 1900–1901.
and actively motile flagellated amoebae. These were translucent oval 25–35 lm with pseudopodia and a polar tuft of flagellae lashing rhythmically 15 times/10 sec (Figure). Methylene blue staining differentiated microorganisms from ciliated bronchial cells. A definite history of contact with cockroaches was admitted by our patient, who denied travel outside India. The parasite was identified as Lophomonas blattarum, and oral metronidazole 400 mg thrice daily was initiated; steady improvement was noted, with absence of protozoa from BAL after one month of therapy. Anti-tuberculosis treatment was continued for 9 months and the patient attained clinical cure. Lophomonas is classified under supergroup Excavata, rank Parabasalia. Trophozoites encyst in adverse conditions and excyst in two motile forms under proper conditions. Given suitable temperature, humidity and oxygen concentration in the human respiratory tract, excysted trophozoites affect protease receptors and interact with tight-junctions.2 The pyriform trophozoite is 20–60 3 12–20 lm in size and bears a polar tuft of flagellae, the body being unstriated in L. blattarum. A trumpet-shaped calyx extends down the central axis and has a nucleus inside. A specialised cytoplasmic collar, the parabasal body, with numerous radiating tubules that support the nucleus-endomembrane system and axial filament, are seen on electron microscopy. This endomembrane assembly probably synthesises enzymes, lysosomes and peroxisomes.2 Various authors have distinguished cells from protozoans by absence of red granules, positivity to ultraviolet light or staining with Heidenham iron hematoxylin, Papanicolaou or Wheatley’s trichome.2,3 We used methylene blue stain and differentiated ciliated bronchial epithelial cells by perceiving motility of trophozoites on rigorous screening of wet mounts within 2 h of sample collection. A segment of alveolar membrane illustrated bronchial cells with static cilia and an embedded trophozoite with motile flagellae. Treatment consists of oral metronidazole 500 mg 8–12 hourly or 2 g daily in adults and 7.5–15 mg/kg every 8 h in children for a week. Severe cases may be treated with intravenous metronidazole 15 mg/kg/h followed by 7.5 mg/kg/6 h as maintenance.1,2,4,5 SANTWANA VERMA, MD* GHANSHYAM VERMA, MD† DIG VIJAY SINGH, MD* JITENDER MOKTA, MD‡ RAMESHWAR SINGH NEGI, MD§ ANUPAMA JHOBTA, MD¶ ANIL KANGA, MD* *Department of Microbiology, †Department of Dermatology ‡Dept. of Internal Medicine §Dept. of Pulmonary Medicine ¶ Department of Radiodiagnosis
369
Figure Translucent, oval to pear-shaped amoeboflagellate, 25–35 lm in size, with pseudopodia and a polar tuft of flagellae seen as a crown. Crenated red blood cells and necrotic material visible (magnification x 400).
Indira Gandhi Medical College Shimla, India e-mail: [email protected] http://dx.doi.org/10.5588/ijtld.14.0513 Conflict of interest: none declared.
References 1 Martinez-Giron R, Esteban J G, Ribas A, Doganci L. Protozoa in respiratory pathology: a review. Eur Respir J 2008; 32: 1354– 1370. 2 Martinez-Giron R, Van Woerden H C. Lophomonas blattarum and bronchopulmonary disease. J Med Microbiol 2013; 63: 1641–1648. 3 Ribas A, Mosquera J A. Amoeboflagellates in bronchial asthma. Acta Cytol 1998; 42: 685–690. 4 Ribas A, Martinez-Giron R, Ponte-Mittelbrum C, AlonsoCuervo R, Iglesias-Llaca F. Immunosuppression, flagellated protozoa in the human airways and metronidazole: observations on the state of the art. [Letter]. Eur Soc Organ Transplantation 2007; 20: 811–812. 5 He Q, Chen X, Lin B, Qu L, Wu J, Chen J. Late onset pulmonary Lophomonas blattarum infection in renal transplantation: a report of two cases. Intern Med 2011; 50: 1039–1043.
Cavitary tuberculosis and tracheal stenosis simulating granulomatosis with polyangiitis We describe a 38-year-old female who presented tracheal stenosis with lung cavities, illustrating the challenges of diagnostic differentiation between tuberculosis (TB) and granulomatosis with polyangiitis (GPA). The patient’s condition began with productive cough on May 2009, leading to progressive dysphonia. Initial acid-fast bacilli (AFB) test was negative. Biopsy of the larynx showed granulomatous laryngitis. In September, the patient’s symptoms had progressed to include dyspnoea, haemoptysis, fever and
370
The International Journal of Tuberculosis and Lung Disease
5 kg weight loss. On examination at our institution, in December 2009, she was 45 kg in weight, dyspnoeic and normotense with physical signs of left apical cavitary disease; the remainder of the examinations were normal. Chest X-rays are shown in the Figure. High-resolution lung computed tomography (CT) showed bilateral apical bullae, inferior right lobe segmentary consolidation and bilateral nodules, 5 mm in diameter (not shown). Blood cell count, urinalysis and blood chemistry were normal, and AFB sputum smear was again negative; erythrocyte sedimentation rate (ESR) was 38 mm/h, C-reactive protein (CRP) was 5.27 mg/l. Spirometry showed severe airflow obstruction, with forced vital capacity (FVC) 47%, forced expiratory volume at 1 second (FEV1) 39%, and FEV1/FVC 67%. Bronchoscopy showed irregular, winding trachea. The biopsy showed mucosal ulcers and chronic granulomatous inflammation. As GPA was suspected, antineutrophil cytoplasmic autoantibody (ANCA) tests were performed. Indirect immunofluorescence (IIF) tests were negative, as were PR3-ANCA and MPO-ANCA (ELISA). Lung biopsy was initially compatible with GPA, but the presence of scarce AFB led to treatment for TB and, a week later, prednisone at intermediate dose (25 mg daily), low-dose methotrexate (12.5 mg/week) and folate 5 mg daily were prescribed for GPA while awaiting the final results of culture. Culture was positive for pan-susceptible Mycobacterium tuberculosis a month later. Careful review of the biopsy concluded that TB was responsible for the clinical picture, and prednisone and methotrexate were rapidly withdrawn. The patient completed standard four-drug anti-tuberculosis treatment in accordance with Mexican standards (isoniazid 300 mg, rifampicin 600 mg, pyrazinamide 1.5 g, ethambutol 1200 mg daily for 2 months, followed by isoniazid 800 mg and rifampicin 600 mg thrice weekly for 20 weeks). The patient experienced full recovery, with negative AFB stains on follow-up, ESR 11 mm/h, CRP 0.17 mg/l and normal liver function tests. In April 2012 the patient had mild dyspnoea, with lung function tests showing severe airflow obstruction with no changes since those performed on admission. Oxymetry was 93%. She gave birth to a normal child, without complications. The lung manifestations of TB and GPA may be indistinguishable, with reports of ANCA positivity in TB, particularly in high-prevalence countries. Their titres, however, are usually low: on IIF less than one third of cases are PR3-ANCA positive.1,2 Although the presence of granulomas and vasculitis was suggestive of GPA, the latter was only found in the sites of caseous necrosis and in blood vessels adjacent to the location of the tubercle bacilli. TB is an occasional cause of infectious vasculitis.3 In GPA, subglottic, and sometimes tracheal, stenosis is characteristic, as opposed to what is observed in TB.4 There are probably no more than 400 reported cases, which contrasts with the high prevalence of
Figure Multiple dispersed nodules are seen in both lung fields. An irregular trachea can be seen, and in at least two levels through its course, stenosis can be seen.
disease worldwide. In our centre, a national reference institution for TB, this case seems to be the first. After treatment for TB the patient’s general and pulmonary condition recovered, although she still needs correction of the tracheal stenosis. In conclusion, the differential diagnosis of GPA must take all elements into account, including histopathological, and be adequately weighted in an individual context. In this case, despite the tracheal stenosis, lung cavities and vasculitis on lung biopsy, ANCA was negative. Treating this patient for GPA could have proved fatal. LUIS FELIPE FLORES-SUA´REZ* ´ SALDARRIAGA RIVERA* LINA MARIA ´ RIVERA ROSALES† ROSA MARIA NATLLELY RUIZ* ˜ ‡ RENATA BA´EZ SALDANA *Primary Systemic Vasculitides Clinic †Department of Pathology and ‡Third Clinical Service Instituto Nacional de Enfermedades Respiratorias Tlalpan, Mexico City, Mexico e-mail: [email protected] http://dx.doi.org/10.5588/ijtld.14.0633 Conflicts of interest: none declared.
References 1 Flores-Sua´rez L F, Cabiedes J, Villa A R, van der Woude F J, Alcocer-Varela J. Prevalence of antineutrophil cytoplasmic autoantibodies in patients with tuberculosis. Rheumatology 2003; 42: 223–229. 2 Pradhan V D, Badakere S S, Ghosh K, Pawar A R. Spectrum of anti-neutrophil cytoplasmic antibodies in patients with pulmonary tuberculosis overlaps with that of Wegener’s granulomatosis. Indian J Med Sci 2004; 58: 283–288. 3 Gordon C, Luqmani R, Fields P, Howie A J, Emery P. Two cases of Wegener’s tuberculosis. Br J Rheumatol 1993; 32: 143–149. 4 Smati B, Sadok M, Ayadi A, et al. Tuberculosis of the trachea. Ann Thoracic Surg 2006; 82: 1900–1901.
