|ECR 2019 / C-2011|
|Chronic Granulomatous disease: pictorial assay of infectious and inflammatory complications|
Findings and procedure details
We retrospectively reviewed 30 patients diagnosed with CGD, 20 of them with X-linked pattern (CYBB) and 10 with autosomal recessive pattern (5 NCF1, 3 NCF2 and 2 CYBA). Mean age at diagnosis was 5.7 years old (ranged from 1 month to 30 years), predominantly male (69%). They had been followed for a mean of 13.7 years (ranged from 2 months to 27 years)
Oxidative capacity evaluated by nitroblue tetrazolium (NBT) slide test was performed in 51,7% of patients (15/29) and it was under 5.6 nM in 86,6% of them (13/15) (normal values > 20 nM)
They most commonly presented with respiratory conditions (Table 1), but they also presented infectious (multiorganic abscesses, sepsis, cervical adenitis) and non-infectious conditions (growth deficiency, hepatosplenomegaly and granulomatous colitis)
After the diagnosis, antibiotic and antifungal prophylaxis was administered. Allogeneic hematopoietic stem cell transplantation was performed in 7 patients (24%).
One patient died of pneumonia and other two patients died of complications after allogeneic stem cells transplantation (massive intracranial hemorrhage and hepatic failure)
Recurrent pneumonias are very common in patients with CGD during childhood, so it is necessary to perform multiple CT and chest radiography for their evaluation. Therefore, the number of ionizating test performed in these patients increases significantly (Table 2). Conventional radiography is also necessary in the initial evaluation of other conditions presented in patients with CGD, like granulomatous colitis, osteomyelitis or liver and splenic abscess, despite the final diagnosis is achieved by other non-ionizing imaging tests (ultrasonography and MRI)
We reviewed literature to analyze radiological features of main conditions presented in patients with CGD and we exemplified them with cases of our cohort of patients:
Acute pneumonia presents as consolidation, reticulonodular and tree-in-bud opacities associated with reactive lymphadenopathies. In severe cases, lung and mediastinal abscesses or necrotizing pneumonia may be present. Miliary pattern may be seen if there is hematogenous spread of infection.
Pulmonary infections by Aspergillus spp are more common in patients with CGD (Fig. 1). Aspergilloma presents as a mass, often mobile and calcified, inside a pre-existing pulmonary cavity (Monod sign) In severe cases, angioinvasive aspergillosis presents with multiple nodules with an halo of ground-glass opacities representing hemorrhage.
Pulmonary nocardiosis is also more common in patients with CGD than in general population (Fig. 2). It is characterized by necrotic and cavitary consolidations, often multiple and bilateral, associated with empyema necessitans and pleural thickening. Multisystemic spread (brain, liver, skin) may be present.
Sequelas of recurrent infections are observed in older patients. CT and conventional radiography show obliterative bronchiolitis (Fig. 3) characterized by bronchial inflammation with submucosal peribronchial fibrosis associated with luminal stenosis and occlusions and pulmonary fibrosis with lung architectural distortion, traction bronchiectasis, reticulation and interlobular septal thickening (Fig. 4). In severe cases, they even may present signs of pulmonary hypertension.
Involvement of lymph nodes
Suppurative lymphadenitis is the second most common condition presented in CGD patients, although symptoms are non-specific and may be under-diagnosed. Cervical is the most common location. Staphylococcus aureus is the most common pathogen detected.
On CT, they presented as enlarged and contrast-enhanced lymph nodes. A central low-density area representing necrosis may be present.
On ultrasonography, lymph nodes presented as enlarged round and hypoechoic lesions with increased signal on color Doppler. Septations and internal debris may be present (Fig. 5).
Chronic non-suppurative lymphadenitis presents as atrophic lymph nodes with calcifications.
Hepatic and splenic manifestations
Hepatosplenomegaly is very frequent in patients with CGD.
Liver and splenic abscesses are more common in patients with CGD than in general population and they are usually multiple. Recurrence rates are higher.
On CT, enhancement pattern differs according to their size: homogeneous in those under 1 cm, peripheral rim of enhancement in those between 1-3 cm and heterogeneous in those over 3 cm. Sometimes, a low attenuation outer ring representing edema of the liver parenchyma is present (double target sign). Segmental, wedge-shaped perfusion abnormalities may be seen.
On MR, they appear hyperintense on T2WI with rim-like contrast-enhancement and central restriction on diffusion, especially the large ones, (Fig. 6)
On ultrasonography, they appear as poorly demarcated hypoechoic lesions with gas bubbles and without central perfusion on colour Doppler. Septations and internal debris may be present (Fig. 6)
Soft tissue and musculoskeletal manifestations
Impetigo, cellulitis, and subcutaneous abscess are the most common soft tissue conditions presented in these patients. Staphylococcus aureus is the most common agent isolated.
On ultrasonography, subcutaneous abscess may be seen as an hypoechoic collection with debris inside and a thickened, hyperechoic and hypervascular wall. Cellulitis of the adjacent subcutaneous tissue and thickening of the skin may be present (Fig. 7).
Miositis is also more frequent in patients with CGD. Enlargement of the muscles with diffuse hyperintensity on T2WI are seen on MR. Intramuscular abscess may also be present.
Osteomyelitis affects lower extremities, ribs and vertebrae due to direct spread from severe pneumonias or soft-tissue collections. Serratia spp. and Aspergillus spp are the most common agents isolated.
On MR, osteomyelitis foci show central fluid collection with intermediate to low signal intensity on T1WI and high signal intensity on T2WI, with rim contrast-enhancement and surrounding bone marrow edema. Cortical bone destruction and soft-tissue collections may be present (Fig. 8).
Recurrent multifocal osteomyelitis (CRMO) is more common in patients with CGD than in general population. It is a diagnosis of exclusion once underlying infection and neoplasia has been ruled out and it presents in children and young adults with female predominance, with a history of chronic multifocal bone pain associated with fever, weight loss or lethargy.
On MR, CRMO presents with bone marrow edema which shows post-contrast enhancement and extends across the physis, associated with soft-tissue edema and periostitis (Fig. 9). Lack of abscess, fistulous tract and bony sequestrum and uncommon locations like clavicle supports the diagnosis of CRMO over infectious osteomyelitis.
Granulomatous colitis is the most common condition of CGD in gastrointestinal tract followed by gastric outlet obstruction due to antral wall thickening. Radiological features can mimic those of inflammatory intestinal disease and peptic ulcer disease, respectively.
Granulomatous inflammation of the upper gastrointestinal tract appears as diffuse edematous wall thickening of the esophagus, best depicted on fluoroscopy with barium swallow (Fig. 10)
Granulomatous colitis present thickening and increased mural contrast-enhancement with additional fibrofatty proliferation and vascular engorgement (Fig. 11). Stenosis, fistulas and abscesses may be present (Fig. 12).
Infection of the urinary system is relatively rare in CGD patients, but repeated urinary tract infections, cystitis, renal and perinephric abscesses may occur (Fig. 13)
A long-term infection of pyelonephritis or renal abscess may lead to renal calcification as a complication.
Haematogenous spread of infections caused by Aspergillus spp. or Staphylococcus aureus can lead to the formation of brain abscess.
Necrotizing otitis externa by Burkholderia cepacia is more common than in general population. On CT, it appears as a diffuse thickening and contrast-enhanced mucosae of the external auditory canal with erosion of the tympanic and mastoid bone.
Sinusal mucormicosis is a rare and severe condition that may be present in patients with CGD. It appears as a sinus opacification with cortical bone erosion and soft-tissue thickening. Gas-fluid levels may be present (Fig. 16)
Septal granulomas may be seen in patients with CGD (Fig. 17). Differential diagnosis with granulomatosis with polyangiitis should be made.
Discoid and systemic lupus erythematosus are more prevalent in patients with CGD than in general population. Other autoimmune conditions present in these patients are immune thrombocytopenia, juvenile idiopathic arthritis, immunoglobulin A nephropathy, and recurrent pericardial effusion.