Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency caused by genetic defects that impact the structural subunits or function of the nicotinamide adenine dinucleotide phosphate oxidase complex. Consequent reduction in respiratory burst impairs phagocyte function, causing granulomatous inflammation and recurrent life-threatening bacterial and fungal infections.1Winkelstein J.A. Marino M.C. Johnston R.B. Boyle J. Curnutte J. Gallin J.I. et al.Chronic granulomatous disease: report on a national registry of 368 patients.Medicine (Baltimore). 2000; 79: 155-169Crossref PubMed Scopus (1164) Google Scholar, 2Magnani A. Brosselin P. Beauté J. Vergnes N. Mouy R. Debré M. et al.Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease.J Allergy Clin Immunol. 2014; 134: 655-662Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 3van den Berg J.M. van Koppen E. Ahlin A. Belohradsky B.H. Bernatowska E. Corbeel L. et al.Chronic granulomatous disease: the European experience.PLoS One. 2009; 4: e5234Crossref PubMed Scopus (465) Google Scholar Although clinically variable with respect to presentation and disease severity,1Winkelstein J.A. Marino M.C. Johnston R.B. Boyle J. Curnutte J. Gallin J.I. et al.Chronic granulomatous disease: report on a national registry of 368 patients.Medicine (Baltimore). 2000; 79: 155-169Crossref PubMed Scopus (1164) Google Scholar,4Martire B. Rondelli R. Soresina A. Pignata C. Broccoletti T. Finocchi A. et al.Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: an Italian multicenter study.Clin Immunol. 2008; 126: 155-164Crossref PubMed Scopus (231) Google Scholar improvement in life expectancy now allows most patients to reach adulthood even without corrective therapy. However, the clinical course of CGD for those who reach adulthood remains poorly documented. In the few large multicenter studies published, data for adults have mainly been combined with pediatric data1Winkelstein J.A. Marino M.C. Johnston R.B. Boyle J. Curnutte J. Gallin J.I. et al.Chronic granulomatous disease: report on a national registry of 368 patients.Medicine (Baltimore). 2000; 79: 155-169Crossref PubMed Scopus (1164) Google Scholar, 2Magnani A. Brosselin P. Beauté J. Vergnes N. Mouy R. Debré M. et al.Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease.J Allergy Clin Immunol. 2014; 134: 655-662Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 3van den Berg J.M. van Koppen E. Ahlin A. Belohradsky B.H. Bernatowska E. Corbeel L. et al.Chronic granulomatous disease: the European experience.PLoS One. 2009; 4: e5234Crossref PubMed Scopus (465) Google Scholar, 4Martire B. Rondelli R. Soresina A. Pignata C. Broccoletti T. Finocchi A. et al.Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: an Italian multicenter study.Clin Immunol. 2008; 126: 155-164Crossref PubMed Scopus (231) Google Scholar, 5Jones L.B. McGrogan P. Flood T.J. Gennery A.R. Morton L. Trasher A. et al.Special Article: Chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry.Clin Exp immunol. 2008; 152: 211-218Crossref PubMed Scopus (168) Google Scholar, 6Wolach B. Gavrieli R. Leeuwen K. Berger-Achituv S. Stauber T. Ari J.B. et al.Chronic granulomatous disease: clinical, functional, molecular, and genetic studies. The Israeli experience with 84 patients.Am J Hematol. 2017; 92: 28-36Crossref PubMed Scopus (59) Google Scholar and the only targeted study of adult CGD outcomes reported high levels of morbidity and early mortality.7Dunogué B. Pilmis B. Mahlaoui N. Elie C. Coignard-Biehler H. Amazzough K. et al.Chronic granulomatous disease in patients reaching adulthood: a nationwide study in France.Clin Infect Dis. 2017; 64: 767-775Crossref PubMed Scopus (38) Google Scholar Because improved survival following corrective hematopoietic stem cell transplantation (HSCT) has expanded this option for treating both asymptomatic children and symptomatic adults with CGD, accurate data for outcomes and quality of life for conservatively managed CGD in adulthood are urgently required to improve counseling for patients and families considering curative treatment. Our objective in this study was to evaluate the long-term clinical course of adult patients with uncorrected CGD in the United Kingdom. Fifty-three patients met the inclusion criteria for our study (details of study methodology can be found in this article’s Methods section in the Online Repository at www.jacionline.org), 44 of whom were cared for at a single center that runs a dedicated CGD clinic. All patients were prescribed continuous antibacterial and antifungal medication, typically cotrimoxazole and itraconazole, for infection prophylaxis. No patients received IFN-γ as prophylaxis. The features of the cohort are summarized in Table I. Data were collected for a total of 891 years of observation, with a mean of 17 years per patient (range, 0.45-54 years).Table IGeneral characteristics of the study populationCharacteristicValueAge at onset of symptoms (y), mean (range)6.2 (0-29)Age at end of follow-up (y), mean (range)33 (16-70)Male, n (%)41 (77)Female, n (%)12 (23)Inheritance and genotype, n (%) X-linked33 (62)CYBB, gp91Phox30 (56.6)No genotype or protein available3 (5.6) Autosomal recessive20 (38)NCF1, p47Phox13 (24.5)NCF2, p67Phox2 (3.8)CYBA, p22Phox1 (2)No genotype or protein available4 (7.5)Mode of presentation, n (%) Skin infection15 (28) Liver abscess9 (17) Pulmonary infection8 (15) Family screening due to index case6 (11) Salmonella gastroenteritis∗One patient also had Salmonella sepsis.4 (8) Colitis3 (6) Lymphadenitis3 (6) Granulomatous obstruction1 (2) Osteomyelitis1 (2) Unknown9 (17)Deaths, n of patients (%)5 (9.4)Mean age (y), range50.7 (38-71)Causes of death, n Respiratory failure4 Pancreatic cancer1CYBA, Gene coding for cytochrome b(-245), α subunit (p22Phox); CYBB, gene coding for cytochrome b(-245), β subunit (gp91Phox); gp91Phox, 91-kDa glycosylated β chain; cytochrome b(-245), β subunit; NCF1, gene coding for neutrophil cytosolic factor 1 (p47Phox); NCF2, gene coding for neutrophil cytosolic factor 2 (p67Phox); p47Phox, neutrophil cytosolic factor 1; p67Phox, neutrophil cytosolic factor 2; p22Phox, 22-kDa nonglycosylated α chain; cytochrome b(-245), α subunit.All patients were prescribed continuous antibacterial and antifungal medication, typically cotrimoxazole and itraconazole, for infection prophylaxis. IFN-γ was not used.One male patient had well-controlled HIV co-infection acquired in adulthood.∗ One patient also had Salmonella sepsis. Open table in a new tab CYBA, Gene coding for cytochrome b(-245), α subunit (p22Phox); CYBB, gene coding for cytochrome b(-245), β subunit (gp91Phox); gp91Phox, 91-kDa glycosylated β chain; cytochrome b(-245), β subunit; NCF1, gene coding for neutrophil cytosolic factor 1 (p47Phox); NCF2, gene coding for neutrophil cytosolic factor 2 (p67Phox); p47Phox, neutrophil cytosolic factor 1; p67Phox, neutrophil cytosolic factor 2; p22Phox, 22-kDa nonglycosylated α chain; cytochrome b(-245), α subunit. All patients were prescribed continuous antibacterial and antifungal medication, typically cotrimoxazole and itraconazole, for infection prophylaxis. IFN-γ was not used. One male patient had well-controlled HIV co-infection acquired in adulthood. A total of 178 infectious events were recorded during 891 years of follow-up, giving an annual incidence of 0.2 infections per patient. The causative pathogen was isolated in only a minority of cases (16%), with Staphylococcus aureus and Aspergillus species most commonly found, as previously described.8Wolach B. Gavrieli R. de Boer M. Gottesman G. Ben-Ari J. Rottem M. et al.Chronic granulomatous disease in Israel: clinical, functional and molecular studies of 38 patients.Clin Immunol. 2008; 129: 103-114Crossref PubMed Scopus (68) Google Scholar Additional details for sites of infection and pathogen can be found in Tables E1 and E2 in this article’s Online Repository at www.jacionline.org. A total of 117 hospitalizations in 37 of 53 patients were seen over the observation period. Pneumonia and exacerbation of chronic pulmonary disease were the major reasons, followed by gastrointestinal (GI) complications and major GI surgeries (for further details, see Table E3 in this article’s Online Repository at www.jacionline.org). Seventy percent of patients had at least 1 hospital admission during the follow-up period (see Fig E1 in this article’s Online Repository at www.jacionline.org), with no correlation between the number of hospital admissions and the duration of follow-up or genetic type of CGD (P > .05). Compliance with treatment was not well documented and therefore could not be assessed as a variable that could influence repeated hospital admissions. A total of 23 patients (43%) had active GI disease in adulthood. Of these, the onset of GI symptoms was documented in childhood for 11 of 23 (48%) and in adulthood for 8 of 23 (35%) (see Table E4 in this article’s Online Repository at www.jacionline.org). Steroids and aminosalicylates were the main medical treatments recorded in adulthood (used in 8 and 11 patients, respectively), with biological agents such as infliximab and adalimumab used in a minority (3 patients recorded). Eleven of 23 (48%) patients with active GI disease in adulthood underwent surgical intervention, which we classified as major (colectomy, ileostomy, colostomy, or proctectomy) or minor (fistula repair or perianal abscess drainage). Of those who required intervention at any time in life, 5 of 11 (45%) had both major and minor surgeries, whereas 3 of 11 (27%) had major surgery only and 3 of 11 (27%) patients required minor surgery only. Most surgical interventions happened in adulthood (21 vs 4 events), but there was no difference in the percentage of patients requiring surgery when pediatric- and adult-onset GI disease was compared. Of importance, 3 episodes of bowel cancer were seen including squamous cell anal carcinoma in a patient aged 30 years with X-linked CGD and perianal fistulas, 1 human papilloma virus–associated anal intraepithelial neoplasia in a patient aged 37 years with X-linked CGD, HIV co-infection, and colitis, and 1 colon adenocarcinoma in a female patient aged 66 years who also had colitis since age 35 years. Separately, testis teratoma was seen in 1 patient at the age of 25 years and pancreatic cancer in a 36-year-old female patient. Pulmonary complications were common in our cohort. Of the 29 patients with computed tomography (CT) scan reports available, 28 (96%) had an abnormality reported. Twenty-two high-resolution CT chest scans of 22 patients were reviewed by a specialist radiologist at our center and scored according to specified criteria. Of these, 15 scans were documented to be performed for routine monitoring purposes and 5 for investigation of acute symptoms (fever, cough, or weight loss). Twenty-one of 22 (95%) chest CT scans were abnormal (see Table E5 in this article’s Online Repository at www.jacionline.org). The most frequent features were nodules (20 patients [90%]), scarring (19 patients [86%]), bronchiectasis (14 patients [64%]), and ground-glass change (10 patients [45%]). Emphysema (9 patients [40%]), air trapping (7 patients [32%]), pleural thickening (2 patients [9%]), and enlarged lymph nodes (1 patient [4.5%]) were also seen in our patients. Of the 9 patients with emphysema with a mean age of 35 years, 4 had no previous history of smoking. A total of 29 patients had respiratory function tests; abnormalities were found in 20 (69%) of these. Obstruction was more frequently seen than restriction (9 vs 6 patients; 45% vs 30%). However, the most frequently observed abnormality was low diffusion capacity, found in 15 of 24 patients tested (62%), and it occurred in 5 patients despite normal spirometry. Further analysis of correlation of CT changes and lung function is presented in Table E5. Importantly, X rays were often normal (11 of 23 [48%]) even in patients with significant changes on CT chest and/or impaired lung function tests, indicating that this modality is not sufficiently sensitive for diagnosis in CGD. Five deaths (9.4%) occurred during the follow-up period, at a mean age of 50.7 years and a median of 47.8 years (range, 36-71 years). Causes of death were respiratory failure secondary to chronic lung disease in 4 cases: 3 in autosomal-recessive CGD and 1 in X-linked CGD at ages 44, 71, 38, and 50 years, respectively. Pancreatic cancer resulted in the death of a patient with autosomal-recessive CGD at age 36 years. Although survival at median age of follow-up (30 years) was 100%, the survival probability for all patients was 94.7%, 88%, 79%, and 59% at ages 36, 38, 44, and 50 respectively (Fig 1). In this cohort, patients with residual respiratory burst were not less likely to die or require major medical intervention (hospital admission for infection, major GI surgery, or HSCT) when compared with patients with absent oxidative burst (see Table E6 in this article’s Online Repository at www.jacionline.org). This is the first study carried out in the United Kingdom aiming to evaluate the long-term clinical course of uncorrected CGD in an adult population, largely looked after at a single center that holds a national CGD service. Noninfectious GI and pulmonary complications were the major causes of serious morbidity in this study. Active chronic inflammatory gut disease in adulthood was more prevalent than in previous studies,3van den Berg J.M. van Koppen E. Ahlin A. Belohradsky B.H. Bernatowska E. Corbeel L. et al.Chronic granulomatous disease: the European experience.PLoS One. 2009; 4: e5234Crossref PubMed Scopus (465) Google Scholar,4Martire B. Rondelli R. Soresina A. Pignata C. Broccoletti T. Finocchi A. et al.Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: an Italian multicenter study.Clin Immunol. 2008; 126: 155-164Crossref PubMed Scopus (231) Google Scholar,7Dunogué B. Pilmis B. Mahlaoui N. Elie C. Coignard-Biehler H. Amazzough K. et al.Chronic granulomatous disease in patients reaching adulthood: a nationwide study in France.Clin Infect Dis. 2017; 64: 767-775Crossref PubMed Scopus (38) Google Scholarfrequently requiring surgical intervention and in some cases associated with GI malignancy, which suggests that patients with GI manifestations would benefit from colonoscopy and magnetic resonance imaging scans screening. Onset in adulthood did not predict less severe disease. Chronic pulmonary complications, highlighted by other studies,5Jones L.B. McGrogan P. Flood T.J. Gennery A.R. Morton L. Trasher A. et al.Special Article: Chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry.Clin Exp immunol. 2008; 152: 211-218Crossref PubMed Scopus (168) Google Scholar, 6Wolach B. Gavrieli R. Leeuwen K. Berger-Achituv S. Stauber T. Ari J.B. et al.Chronic granulomatous disease: clinical, functional, molecular, and genetic studies. The Israeli experience with 84 patients.Am J Hematol. 2017; 92: 28-36Crossref PubMed Scopus (59) Google Scholar, 7Dunogué B. Pilmis B. Mahlaoui N. Elie C. Coignard-Biehler H. Amazzough K. et al.Chronic granulomatous disease in patients reaching adulthood: a nationwide study in France.Clin Infect Dis. 2017; 64: 767-775Crossref PubMed Scopus (38) Google Scholar, 8Wolach B. Gavrieli R. de Boer M. Gottesman G. Ben-Ari J. Rottem M. et al.Chronic granulomatous disease in Israel: clinical, functional and molecular studies of 38 patients.Clin Immunol. 2008; 129: 103-114Crossref PubMed Scopus (68) Google Scholar, 9Liese J. Kloos S. Jendrossek V. Petropoulou T. Wintergerst U. Notheis G. et al.Long-term follow-up and outcome of 39 patients with chronic granulomatous disease.J Pediatr. 2000; 137: 687-693Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar were almost unanimous in our cohort, with a high prevalence of presumed noninfectious inflammatory changes on high-resolution CT, including early onset of emphysema seen even in the absence of smoking. Low diffusion capacity was seen both with and without CT changes and despite normal spirometry, suggesting that this might be an early indicator of inflammatory lung disease and a useful tool to monitor these patients. Of importance, the 9.4% overall mortality rate observed in our conservatively managed CGD cohort was predominantly related to chronic respiratory failure. Overall, our data indicate that adults with CGD live with significant and progressive morbidity, predominantly related to inflammatory complications. With rapidly improving outcomes for HSCT in CGD and progress with gene therapy approaches, the long-term complications associated with uncorrected CGD are an important consideration when counseling patients and families for stem cell treatments. We thank Mrs Karin van Leeuwen, Mr Martin de Boer, and Prof. Dirk Roos from Sanquin Research, Amsterdam, The Netherlands, for determining the genetic mutations in the patients. Download .docx (.03 MB) Help with docx files Online Repository Download .docx (.05 MB) Help with docx files Fig E1 Download .docx (.05 MB) Help with docx files Tables E1-E6 and Legend for Fig E1

In the original version of this article unfortunately two authors were missing: Dr. Jürgen Weidemann and Dr. Daniel Berthold. The correct list of authors is presented above.

Pulmonary hypertension is a serious condition with multiple underlying aetiologies which require different treatment strategies. We present a case of severe idiopathic pulmonary arterial hypertension in a 20-year-old patient with ongoing breathlessness. She was initially diagnosed with asthma and panic attacks in community care. As the symptoms became progressively worse, she was referred for pulmonary hypertension clinic assessment. Ventilation/perfusion single-photon emission computed tomography (V/Q SPECT) showed grossly abnormal perfusion defects which were mismatched to the ventilation scan, suggestive of chronic thromboembolic disease. However, corroborating computed tomographic (CT) pulmonary angiogram and invasive pulmonary angiography showed no thromboembolic disease. Histological examination of the pulmonary arteries post-mortem showed changes consistent with idiopathic pulmonary arterial hypertension. This case highlighted the clinical challenges in interpreting the investigation results and phenotyping pulmonary hypertension. V/Q SPECT might have a role in visualising the extent of vasculopathies in pulmonary arterial hypertension.

Background: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. Objective: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. Methods: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. Results: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16%(n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affectedmutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression. Conclusions: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials.

A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded." There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51).

Objectives:SSc-pulmonary arterial hypertension (SSc-PAH) is associated with worse response to therapy and survival when compared with idiopathic PAH. It is suggested that the vasculopathy in SSc may involve postcapillary pulmonary venules resulting in pulmonary veno-occlusive disease (PVOD). This may underlie the lower gas transfer and worse outcome on therapy. We sought to test whether CT signs of PVOD (CTS-PVOD) were frequent in SSc-PAH and whether they were associated with pulmonary oedema on therapy and worse survival.Methods:CT thorax of 66 SSc patients with precapillary pulmonary hypertension (PH) were blindly scored by two radiologists for CTS-PVOD (⩽1 or ⩾ 2). Case note and radiograph review determined the presence of pulmonary oedema on therapy.Results:Fifty-nine patients (89%) had ⩽1 CTS-PVOD and only 7 (11%) had ⩾2 CTS-PVOD. Pulmonary oedema on therapy was relatively common in those with ⩾2 CTS-PVOD. On univariate analysis ⩾2 CTS-PVOD were associated with a trend towards worse survival.Conclusion:CTS-PVOD were less frequent in this SSc-PAH cohort than in previous reports but the presence of at least two of these signs is associated with pulmonary oedema on therapy and a trend towards worse survival on univariate analysis.

Rationale. In healthy individuals, the density of pulmonary parenchyma at computed tomography (CT) in the dependent lung is higher than the density in the nondependent lung, reflecting a gravity-dependent density gradient. Abnormal pulmonary perfusion is known to result in regional differences in CT density. We evaluated possible disturbances in the normal CT density gradient in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods. We analyzed non-contrast enhanced thin section CTs of 7 patients with IPAH - established on right heart catheterisation - and 8 healthy controls. Regions of interest (ROI) were selected in the most dependent and nondependent areas at two levels: aortic arch and pulmonary venous confluence. The mean densities in Hounsfield Units (HU) for the ROIs in each lung region were obtained and their average was taken as the mean density for that region. Average densities were calculated for the dependent and non-dependent ROIs in each level and zonal and global density gradients were derived. Results. Patients with IPAH were characterized by a decreased density gradient compared to the healthy individuals, at the level of aortic arch (median, 15.3 versus 35.6, p = .04), the level of pulmonary venous confluence (median, 29.1 versus 46.3, p = .02) and globally (median, 24.6 versus 42.9, p = .03). Conclusion. Patients with IPAH have a significantly reduced gravity-dependent density gradient compared to healthy individuals. This observation suggests that the normal gradient is largely dependent on the structural integrity and compliance of the pulmonary vasculature.

Some patients with primary antibody deficiency (PAD) syndromes develop bronchiectasis. In immunocompetent patients with bronchiectasis, key clinico-pathophysiological relationships exist between exacerbation frequency, lung function, health-status, infection and inflammation. It is not known whether such relationships are present in PAD. It is also not known how local and systemic inflammation in PAD compares with that in immunocompetent (non-PAD) bronchiectasis patients.

An 82-year-old woman was transferred from her local hospital to our National Pulmonary Hypertension Service because of the suspicion of pulmonary hypertension. A month previously, she attended her local Accident & Emergency Department with a minor injury to her left leg. During triage an oxygen saturation of 85% was noted. She was cyanotic but she did not report any breathlessness, respiratory rate was in a normal range, and she was normotensive. On history she reported being limited when walking, which she considered normal for her age and she remained fully independent. Chest X-Ray (Figure 1) showed a large hernia that occupied central and right chest, raising suspicions of a Bochdalek hernia. High-resolution computed tomography and computed tomography pulmonary angiogram were performed and confirmed the presence of a large postero-lateral Bochdalek hernia with the stomach and portions of small and large bowel occupying a substantial portion of the right thoracic cavity and associated with right lung hypoplasia (Figure 2A–2D).There was no evidence …

What is the differential diagnosis in a 45 year-old man with dry cough, breathlessness, and this chest x-ray? During investigation it became apparent that he was infected with HIV. How does this change management and when would you start anti-retroviral therapy? Keep up-to-date and test your skills in this interactive case.