Medical Image of the Month: Late-Onset Pompe Disease

Figure 1. Non-contrasted CT scans. A: Chest CT demonstrates a large mucous plug in the left mainstem bronchus (blue arrow) resulting in complete collapse of the left lung. There is near complete fatty replacement of the musculature of the shoulder girdles except for a small residual portion of the left infraspinatus muscle (red arrow). B: Abdominal CT demonstrates fatty replacement of the rectus abdominis musculature (red arrows) and lumbar musculature (blue arrows) consistent with the patient’s history of Pompe disease. C: Pelvic CT demonstrates near complete fatty replacement of the muscular compartments of the thigh except for residual portions of the bilateral sartorius muscles (blue arrows).

Clinical Presentation: A 63-year-old lady with a past medical history significant for late-onset Pompe disease complicated by chronic hypoxemic and hypercarbic respiratory requiring continuous mechanical ventilation via a tracheostomy tube presented to the emergency room from her care facility with worsening hypoxemia. She had been feeling poorly for three days prior to her presentation with fevers, chills, and thicker secretions from her tracheostomy tube with routine suctioning.

On arrival, she was febrile with a temperature of 39 °C and had diminished breath sounds on the left. Her lab work demonstrated a leukocytosis along with an increase in her creatinine consistent with acute kidney injury. CT scans of the chest, abdomen, and pelvis (Figure 1) demonstrated collapse of the left lung secondary to a large mucous plug in the left mainstem bronchus and fatty replacement of most of her visualized skeletal musculature consistent with her diagnosis of Pompe disease. Sputum cultures grew Pseudomonas aeruginosa. Through a combination of fluid resuscitation, antibiotics, and aggressive chest physiotherapy her clinical condition improved to the point that she was able to return to her care facility.

Discussion: Pompe disease results from a deficiency of acid alpha-glucosidase (GAA) which leads to the accumulation of glycogen resulting in tissue destruction (1,2). Adult patients present with progressive, proximal weakness in a limb-girdle distribution (particularly the hip flexors) along with respiratory insufficiency secondary to diaphragmatic involvement (3,4). Some patients may require noninvasive respiratory support and may progress to requiring mechanical ventilation (5). Diagnosis is made by clinical history and electromyogram. The rate of progression and sequence of respiratory and skeletal involvement vary substantially. Intravenous enzyme replacement therapy with alglucosidase alfa has shown efficacy for late-onset Pompe disease. Gene therapy is under investigation. In untreated patients with late-onset disease, the estimated 5-year survival is 95% and 40% at 30 years (6).

Zachary Hernandez MD, Kelly Wickstrom DO, and Tammer El-Aini MD.

Department of Pulmonary Medicine and Critical Care

University of Arizona College of Medicine

Tucson, AZ USA

References

1. Hirschhorn R, Reuser A. Glycogen storage disease type II: Acid alpha-glucosidase (acid maltase) deficiency. In: The metabolic and molecular bases of inherited disease, Scriver C, Beaudet A, Sly W, Valle D (Eds), McGraw-Hill, New York 2001. p.3389.
2. Raben N, Plotz P, Byrne BJ. Acid alpha-glucosidase deficiency (glycogenosis type II, Pompe disease). Curr Mol Med. 2002 Mar;2(2):145-66. [CrossRef] [PubMed]
3. Engel AG. Acid maltase deficiency in adults: studies in four cases of a syndrome which may mimic muscular dystrophy or other myopathies. Brain. 1970;93(3):599-616. [CrossRef] [PubMed]
4. Winkel LP, Hagemans ML, van Doorn PA, Loonen MC, Hop WJ, Reuser AJ, van der Ploeg AT. The natural course of non-classic Pompe's disease; a review of 225 published cases. Neurol. 2005 Aug;252(8):875-84. [CrossRef] [PubMed]
5. Mellies U, Stehling F, Dohna-Schwake C, Ragette R, Teschler H, Voit T. Respiratory failure in Pompe disease: treatment with noninvasive ventilation. Neurology. 2005 Apr 26;64(8):1465-7. [CrossRef] [PubMed]
6. van der Meijden JC, Güngör D, Kruijshaar ME, Muir AD, Broekgaarden HA, van der Ploeg AT. Ten years of the international Pompe survey: patient reported outcomes as a reliable tool for studying treated and untreated children and adults with non-classic Pompe disease. J Inherit Metab Dis. 2015 May;38(3):495-503. [CrossRef] [PubMed]

Cite as: Hernandez Z, Wickstrom K, El-Aini T. Medical image of the month: late-onset Pompe disease. Southwest J Pulm Crit Care. 2020;20(4):124-5. doi: https://doi.org/10.13175/swjpcc022-20 PDF 

November 2018 Imaging Case of the Month: Respiratory Failure in a 36-Year-Old Woman

Michael B. Gotway, MD

Department of Radiology

Mayo Clinic Arizona

Scottsdale, AZ USA

Clinical History: A 36–year old woman presented with complaints of shortness of breath and worsening dyspnea on exertion. She had a reported history of central nervous system vasculitis of uncertain etiology, treated with azathioprine and prednisone currently, and cyclophosphamide in the past. Her symptoms reportedly responded well to this regimen. Her diagnosis of central nervous system vasculitis was established 6 months earlier when the patient presented with upper extremity paresthesia, headache, left arm weakness, diplopia, and a right eye visual field deficit, evidently with brain imaging showing some pathologic changes, although those records were not available at her presentation. Reportedly she responded well to her immunosuppressive therapy and her steroid and azathioprine doses had been tapered accordingly. Her past medical history was otherwise remarkable for a history of migraine headaches, depression, childhood asthma, hemorrhagic cystitis due to cyclophosphamide (which prompted discounting this drug in favor of azathioprine for the purported central nervous system vasculitis) in the past, and endometriosis.

The patient is a former smoker for a total of 5 pack-years, quitting years previously. She is the mother of a 3-year-old child. The patient denied alcohol and drug use. A history of penicillin allergy was elicited. In addition to azathioprine and prednisone, her medications included inhaled budesonide, Bactrim, escitalopram, topiramate, and sumatriptan/naproxen sodium as well as a multivitamin. There was some history of fenfluramine/phentermine (“Fen-Fen”) use years earlier.

Her physical examination was largely unremarkable. The patient complained of head pain and was visibly mildly dyspneic, but her lungs were clear and no abnormal heart sounds were detected. Her extremities appeared normal- no ecchymosis, cyanosis, or clubbing was detected. She did have some prior history suggesting the presence of erythema nodosum, now presenting as an erythematous region on the right lower extremity, which underwent biopsy, although changes characteristic of erythema nodosum were not present at her current examination. Reportedly this region had been injured when she bumped the right lower extremity on a chair, and this injury evidently became infected, requiring drainage, yielding cultures positive for Staphylococcus aureus and, about 1 month later, Actinomyces israelii. Her vital signs should normal pulse rate and blood pressure, breathing at 26 breaths / minute. Her room air oxygen saturation was 93%.

Frontal and lateral chest radiography (Figure 1) was performed.

Figure 1. Frontal (A) and lateral (B) chest radiography.

Which of the following represents the most accurate assessment of the chest radiographic findings? (Click on the correct answer to be directed to the second of twelve pages)

1. Chest radiography shows basilar fibrotic opacities
2. Chest radiography shows bilateral pleural effusions
3. Chest radiography shows cavitary pulmonary lesions
4. Chest radiography shows marked cardiomegaly
5. Chest radiography shows numerous small nodular opacities

Cite as: Gotway MB. November 2018 imaging case of the month: Respiratory failure in a 36-year-old woman. Southwest J Pulm Crit Care. 2018;17(5):119-33. doi: https://doi.org/10.13175/swjpcc114-18 PDF

Medical Image of the Week: Bronchiectasis

Figure 1. Video of thoracic axial computed tomography (CT) images in lung windows demonstrating dependent cystic bronchiectasis with air-fluid levels.

Figure 2. Video of thoracic coronal CT images.

A 49-year old Native American woman with chronic hypoxic and hypercarbic respiratory failure requiring 3 liters continuous via nasal cannula and nocturnal non-invasive bi-level ventilation presented with acute shortness of breath for 5 days. She has history of recurrent respiratory infections since early childhood, however over the past five years has been treated multiple times for presumed COPD exacerbation with last such treatment one month prior to admission.

Upon arrival, vitals displayed elevated blood pressure 183/96. Clinical examination demonstrated morbidly obese patient in mild somnolence and has diffuse expiratory wheezing, basal crackles with reduced air entry bilaterally. Laboratory examination showed leukocytosis (13,800 cells/uL) with neutrophilic predominance, thrombocytopenia (85,000 cells/uL), and elevated bicarbonate (31 mg/dL). Arterial blood gas showed pH=7.29, pCO2 756 mm Hg, and pO2 73 mm Hg. Thoracic computed tomography (CT) with contrast ruled out pulmonary embolism, however demonstrated extensive cystic bronchiectasis in left upper and lower lobes, right lower lobe along with findings consistent with chronic bronchitis and bronchiolitis. (Figures 1 and 2)

Bronchiectasis workup showed-low serum globulins (IgG 388 mg/dL, IgM 18 mg/dL , IgA 64 mg/dL, with low IgG-1 226 mg/dL, IgG-2 140 mg/dL). Alpha Antitrypsin level was high. Blood culture, sputum culture, urine Legionella, Streptococcus pneumoniae antigen, Coccidioidomycosis serology, quantiferon and AFB stain for TB were all negative. Aggressive nebulization therapy, intermittent Bi-level positive airway pressure and antibiotics allowed her to become stabilized to a baseline oxygen requirement. She was  discharged with diagnosis of acute on chronic hypoxic and hypercarbic respiratory failure secondary to flare up of severe bronchiectasis secondary to common variable immunodeficiency (CVID).

Common Variable Immunodeficiency (CVID), a subset of primary humoral immunodeficiency diseases, is a condition of inadequate immunoglobulin expression in response to antigen exposure. Prevalent equally amongst the sexes and ranges from 1 in 10,000 to 50,000 with bimodal incidence either within the first or third decade of life. Initial history is nonspecific, consisting of recurrent episodes of sinusitis and bronchitis with severity of illness dependent on level of immunoglobulin expression. The European Society for Immunodeficiency defines CVID as reduced (below 2 standard deviations of the mean) levels of IgG with reduced IgA and/or IgM, together with failure to mount a significant antibody response to vaccination, in the absence of a known cause. However, etiology of CVID is still incompletely understood and given the clinical heterogeneity in patient presentation, there is lack of consensus on clinical definition. Persistent sinus or respiratory complaints, in combination with finding of airway bronchiectasis lead a referral to an immunologist or pulmonologist in pursuit of diagnosis.

Bronchiectasis, a syndrome characterized by irreversible destruction, abnormal dilatation impairing clearance and leading to mucous pooling, is a common development in this impaired immune condition. Management of disease is multifactorial with symptom control, administration of appropriate immunizations and immunoglobulin replacement in agammaglobulinemia in order to curb recurrence of infections. Pulmonary morbidity due to bronchiectasis is common, however role of lung transplant in this patient population is unknown.

Practitioners should remain cognizant of considering CVID in patients with history of recurrent pneumonias and imaging findings of bronchiectasis to hasten specialty referral early and minimize pulmonary morbidity.

Faraz Jaffer, MD. Nirmal Singh, MD. and Jennifer Huang-Tsang, MD.

Department of Internal Medicine

University of Arizona at South Campus

Tucson, Arizona USA

References

1. Panigrahi MK. Common variable immunodeficiency disorder - An uncommon cause for bronchiectasis. Lung India. 2014 Oct;31(4):394-6. [CrossRef] [PubMed]
2. Tarzi MD, Grigoriadou S, Carr SB, Kuitert LM, Longhurst HJ.Clinical immunology review series: An approach to the management of pulmonary disease in primary antibody deficiency. Clin Exp Immunol. 2009 Feb;155(2):147-55. [CrossRef] [PubMed]
3. Cunningham-Rundles C. How I treat common variable immune deficiency. Blood. 2010 Jul 8;116(1):7-15. [CrossRef] [PubMed]

Cite as: Jaffer F, Singh N, Huang-Tsang J. Medical image of the week: bronchiectasis. Southwest J Pulm Crit Care. 2016;12(6):258-60. doi: http://dx.doi.org/10.13175/swjpcc045-16 PDF

Medical Image of the Week: Necrotizing Pancreatitis

Figure 1. Contrast-enhanced CT of the abdomen and pelvis demonstrates innumerable foci of gas adjacent to the pancreatic head/body junction (red arrow) with marked inflammation of the pancreatic head (blue arrow). These findings are consistent with necrotizing pancreatitis.

A 60-year-old man with a past medical history significant for coronary artery disease status post percutaneous coronary intervention was admitted to Banner University Medical Center for acute pancreatitis complicated by a pericardial effusion requiring pericardiocentesis. The following day, the patient developed severe shortness of breath requiring increasing amounts of supplemental oxygen. The patient was emergently transferred to ICU for noninvasive bilevel positive airway pressure ventilation, but he subsequently required intubation. Throughout his worsening condition, he denied any abdominal pain, only relaying ongoing substernal chest pain. His troponins, however, remained negative and echocardiography failed to show any reaccumulation of the pericardial effusion.

CT scan of the chest failed to show any pulmonary embolism. But, CT abdomen displayed acute pancreatitis complicated by peripancreatic gas consistent with necrotizing pancreatitis (Figure 1). Emergent laparotomy was completed. There were no signs of stomach or duodenal perforation. Purulent fluid was removed from the lesser sac and an irrigating stump was placed.

Hem Desai MD¹, Tammer Elani MD¹, Nour Alhoda Parsa MD¹ and Kareem Ahmad MD²

¹Department of Internal Medicine and ²Division of Pulmonary, Allergy, Critical Care and Sleep Medicine

University of Arizona

Tucson, AZ

Reference

1. Thoeni RF. The revised Atlanta classification of acute pancreatitis: Its importance for the radiologist and its effect on treatment. Radiology. 2012;262(3):751-64. [CrossRef] [PubMed]

Reference as: Desai H, Elani T, Parsa NA, Ahmad K. Medical image of the week: necrotizing pancreatitis. Southwest J Pulm Crit Care. 2015;11(2):84-5. doi: http://dx.doi.org/10.13175/swjpcc080-15 PDF

Medical Image of the Week: Leukemic Infiltrates

Figure 1. AP portable chest x-ray demonstrating diffuse bilateral infiltrates.

Figure 2. Histology showing extensive interstitial and perivascular lymphocytic infiltrates.

Figure 3. Immunohistochemical staining for CD8 positive T-cell immunophenotype.

A 50 year-old white man with newly diagnosed, acute T-cell prolymphocytic leukemia presented with progressive exertional dyspnea and non-productive cough. The patient was due to meet with his hematologist that day to discuss initiation of treatment. The patient had not noted fever, chills, night sweats, chest pain, or lower extremity swelling. Blood pressure was 112/60 mm Hg, respiratory rate was 36/minute and labored, pulse was 110/minute and temperature was 37 degrees Celsius. Oxygen saturation measured by pulse oximetry was 62% on room air at rest, and rose to 90% after the application of a 100% non-rebreather mask. Diffuse rales were present on chest auscultation. Marked splenomegaly was present on abdominal examination. Peripheral white blood count was 112.2 K/ul with 99% lymphocytes. Smudge cells were noted. Hemoglobin was 12.9 g/dl and platelet count was 93K/ul. Procalcitonin level was 0.3 pg/ml. The chest radiograph demonstrated diffuse bilateral infiltrates (Figure 1). The patient developed rapidly progressive hypoxemia, was intubated orally, and mechanical ventilation was initiated. Lung biopsies were performed via a video-assisted thoracic surgical approach of the right middle and right lower lobes. Microscopic examination demonstrated extensive leukemic infiltration of the pulmonary interstitium and perivascular space (Figure 2). Immunohistochemical staining showed that the infiltrating cells expressed a CD8 positive T-cell immunophenotype (Figure 3) pattern similar to the patient’s peripheral blood flow cytometry study. Therapy began with an escalating dose of alemtuzumab and intermittent pentostatin, but the patient developed progressive multi-organ failure and expired.

Acute T-cell prolymphocytic leukemia is an aggressive mature T-cell leukemia usually characterized by peripheral blood lymphocytosis and splenomegaly (1). Extramedullary involvement most commonly affects the skin (2). Diffuse interstitial and perivascular pulmonary involvement with respiratory failure has not been previously reported. Pathological involvement of the pulmonary interstitial space should be considered in patients with acute T-cell prolymphocytic leukemia and respiratory insufficiency.

Charles J. VanHook1, Carlyne Cool2, Todd DeBoom3, Robert Fisher4, and

Douglas J. Tangel1

1Department of Intensive Care Medicine

Longmont United Hospital

Longmont, CO

2Department of Pathology and Department of Medicine

University of Colorado and National Jewish Health

Denver, CO

3Department of Pathology

Longmont United Hospital

Longmont, CO

4Department of Oncology

Longmont United Hospital

Longmont, CO

References

1. Dearden CE. T-cell prolymphocytic leukemia. Med Oncol. 2006;23(1):17-22. [CrossRef] [PubMed]
2. Valbuena JR, Herling M, Admirand JH, Padula A, Jones D, Medeiros LJ. T-cell prolymphocytic leukemia involving extramedullary sites. Am J Clin Pathol. 2005;123(3):456-64. [CrossRef] [PubMed]

Reference as: VanHook CJ, Cool C, DeBoom T, Fisher R, Tangel DJ. Medical image of the week: leukemic infiltrates. Southwest J Pulm Crit Care. 2015;10(5):235-7. doi: http://dx.doi.org/10.13175/swjpcc043-15 PDF

Medical Image of the Week: Constrictive Pericarditis

Figure 1. A computerized tomography of the chest revealed cardiomegaly, bilateral pleural effusions and pericardial calcification noted diffusely with focal regions of pericardial thickening greater than 4 mm.

A 62-year-old woman, with a past medical history significant for oxygen dependent COPD, paroxysmal atrial fibrillation, and obstructive sleep apnea, presented to the hospital with hypoxemic respiratory failure requiring intubation and mechanical ventilation. A computerized tomography of the chest revealed cardiomegaly, bilateral pleural effusions, and pericardial calcification that was noted diffusely with focal regions of pericardial thickening greater than 4 mm. A cardiac catheterization revealed elevated right-sided pressure; markedly elevated left ventricular end diastolic pressure; equalization of LV-RV diastolic pressures; and sharp Y descent on the right atrial pressure waveform; which is all suggestive of constrictive physiology.  The patient was medically optimized and diuresed and eventually underwent a successful pericardiectomy.

Mohammed Alzoubaidi MD, John Bloom MD, Jarrod Mosier MD, Linda Snyder MD

Department of Pulmonary and Critical Care Medicine, University of Arizona,

Tucson, AZ

Reference as: Alzoubaidi M, Bloom J, Mosier J, Snyder L. Medical image of the week: constrictive pericaditis. Southwest J Pulm Crit Care. 2014;8(5):280. doi: http://dx.doi.org/10.13175/swjpcc042-14 PDF

Medical Image of the Week: Hemophagocytic Lymphohistiocytosis (HLH)

Figure 1. Axial (Panel A) and coronal (Panel B) PET-CT Scan Images showing numerous metabolically active pulmonary nodules and mediastinal lymph nodes.

Figure 2. Axial (Panel A) and Sagittal (Panel B) images of the chest CT showing consolidative pulmonary nodules with surrounding ground glass halo and mediastinal lymphadenopathy.

Figure 3. Bone Marrow Biopsy (x1000). Panel A: macrophage engulfing a neutrophil. Panel B: macrophage engulfing erythrocyte debris.

Figure 4. Panel A: Lower power view of the lung biopsy (H&E stain) showing the interface between the neoplastic lymphocytic infiltrate and benign, normal lung. Panel B: high power view showing the neoplastic B-cell lymphoma with sheets of large lymphocytes.

A 41-year-old African American woman with a history of diffuse large B cell lymphoma in remission was admitted to the hospital with severe dyspnea and abdominal pain. Recent imaging revealed extensive pulmonary and liver nodules with significant mediastinal lymphadenopathy (Figures 1 and 2).  She had an extensive outpatient evaluation of these abnormalities including multiple percutaneous and endoscopic biopsies which were nondiagnostic.  She deteriorated clinically and a ferritin level was elevated at 36,284 ng/mL.  Due to the markedly elevated ferritin, a bone marrow biopsy was performed and was normocellular with trilineage hematopoiesis and erythrophagocytosis consistent with hemophagocytic lymphohistiocytosis (HLH, Figure 3).  A VATS guided lung biopsy was performed revealing recurrence of the diffuse large B cell lymphoma (Figure 4).  She started chemotherapy with the E-SHAP (etoposide, methylprednisolone, cytarabine, cisplatin), however, became severely pancytopenic and developed acute respiratory failure, shock and multi-organ failure.  She died despite aggressive care in the intensive care unit.  Patients with HLH often present with sepsis like symptoms and multiorgan failure.  Measurement of serum ferritin level is a critical test in suggesting the diagnosis once infection is excluded.  Early recognition and prompt treatment is essential to preventing fatal outcomes.

Tauseef Afaq Siddiqi, MD¹; Carlos Tafich Rios, MD²; Carlos L Cantu, MD³; James Knepler, MD¹; Linda Snyder, MD¹

¹ Division of Pulmonary, Allergy, Critical Care and Sleep Medicine,

² Department of Medicine,

³ Department of Pathology, The University of Arizona, Tucson, AZ 85724, USA.

References

1. Raschke RA, Garcia-Orr R. Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults. Chest. 2011;140(4):933-8. [CrossRef] [PubMed] 
2. Okabe T, Shah G, Mendoza V, Hirani A, Baram M, Marik P. What intensivists need to know about hemophagocytic syndrome: an underrecognized cause of death in adult intensive care units. J Intensive Care Med. 2012;27(1):58-64. [CrossRef] [PubMed]

Reference as: 

Siddiqi TA, Rios CT, Cantu CL, Knepler J, Snyder L. Medical image of the week: hemophagoctyic lymphohistiocytosis (HLH). Southwest J Pulm Crit Care. 2013;7(6):351-2. doi: http://dx.doi.org/10.13175/swjpcc157-13 PDF

Medical Image of the Week: Septic Emboli from Elbow Abscess

Figure 1. Panel A: Multiple thick wall cavities. Panel B: pneumothorax (arrows).

A 45 year old man with past medical history of rheumatoid arthritis and intravenous drug use presented with a several week history of progressive right elbow pain. He underwent incision and drainage with an operative diagnosis of septic arthritis.  He developed postoperative respiratory failure requiring prolonged mechanical ventilation.  Wound and blood cultures grew methacillin-resistant Staphylococcus aureus.  CT Chest revealed multiple thick walled cavities (A) from septic emboli as well as rupture of a pneumatocele causing a pneumothorax (B, arrows) necessitating chest tube insertion.

John F. Rosell, MD, Janet Campion, MD and Philip Factor, DO

Departments of Medicine and Emergency Medicine

University of Arizona

Tucson, AZ

Reference as: Rosell JF, Campion J, Factor P. Medical image of the week: septic emboli from elbow abscess. Southwest J Pulm Crit Care. 2013;7(1):27. doi: http://dx.doi.org/10.13175/swjpcc088-13 PDF