Monogenic autoinflammatory diseases in children: single center experience with clinical, genetic, and imaging review

Abstract

Purpose: 1. To review the contemporary literature and present a list of the imaging findings for patients with autoinflammatory diseases from our hospital. All these patients are found to have a genetic mutation that is responsible for their disease. 2. To present follow-up imaging findings, when available, and correlate those with symptoms and type of treatment administered in approximately 40 patients with autoinflammatory diseases of a single tertiary pediatric health care center including familial Mediterranean fever, Cryopyrin-associated autoinflammatory syndrome, PAPA (pyogenic arthritis, pyoderma gangrenousum, and acne) syndrome, and more. These findings are related to disease progression, treatment response, or treatment-induced changes.

Conclusion: Autoinflammatory diseases are relatively rare entities that can affect any system of the body. Given the many nonspecific imaging features, awareness of these diseases and good communication with clinicians aid in reaching an accurate diagnosis.

Keywords: Autoinflammatory diseases; Children; Fever; Radiology; Rheumatology.

Fig. 1

List of autoinflammatory diseases discussed in the paper of patients of our cohort according to the body system involved as a primary disease-related manifestation and specific locations in these body systems

Fig. 2

Familial Mediterranean fever. Selected axial CT image of the abdomen after oral and intravenous contrast administration in a 14-year-old girl presenting to the Emergency department with acute abdominal pain showing small ascites (white arrows) and diffuse intra-abdominal fat stranding (black arrows). Solid organs, bowel, and appendix were normal (not shown). Findings represent peritonitis without detectable underlying cause

Fig. 3

A 17-year-old girl with Familial Mediterranean Fever. a Coronal oblique Short-Tau inversion recovery (STIR) of the sacroiliac joints demonstrates abnormal subarticular bone marrow signal (arrows). b Coronal T1-post intravenous gadolinium administration demonstrates bone marrow (arrows) and synovial (arrow heads) enhancement. Findings are consistent with sacroiliitis

Fig. 4

A 1-year-old girl newly diagnosed with neonatal onset multisystem inflammatory disease (NOMID), first presenting with recurrent fever and urticarial rash. MRI of the brain including internal auditory canals was performed as part of the assessment. a Selected axial 3D T1- post intravenous gadolinium administration demonstrates subtle enhancement of the cochlear nerves bilaterally (arrows). b Enhancement resolved in 6 years follow up after treatment with anakinra

Fig. 5

A 2-year-old girl with Blau syndrome presenting with swelling of the hands, knees, and ankles. a Frontal radiograph of the right hand demonstrates diffuse periarticular osteopenia, soft tissue swelling around the proximal interphalangeal joints (arrows). No joint space narrowing, erosions or osseous destruction. Similar changes were present in the left hand (not shown). b Lateral radiograph of the right knee demonstrates large suprapatellar joint effusion (arrow) and soft tissue swelling. Similar changes were seen in the left knee (not shown). c Lateral radiograph of the right ankle demonstrates soft tissue swelling along the tendons representing tenosynovitis (arrows). d Axial T1-weighted image with fat suppression after intravenous contrast administration of the right wrist demonstrate thickening and enhancement of the tendon sheaths of all the extensor tendons (arrows) representing tenosynovitis. e follow up frontal radiograph of the right hand of the same patient at the age of 25 years demonstrates typical flexion contracture of the PIP joints of the fourth and fifth digits (arrows). Note that there are no erosions

Fig. 6

Different presentations of osteoarticular inflammatory involvement in a girl with pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome. a Coronal STIR of the anterior right knee demonstrates moderate effusion with synovial thickening (arrows) and surrounding soft tissue edema. b Axial STIR image at the mid-level of the metacarpals of the left hand demonstrates abnormal bone marrow signal of the fourth metacarpal bone with an associated loculated dorsal fluid collection that demonstrates a fluid-fluid level (arrow). c Sagittal T1-weighted image with fat suppression and intravenous contrast administration through the fourth metacarpal bone at the same presentation demonstrates ring enhancement of the dorsal fluid collection (black arrow). Moreover, there is extensive synovial thickening and enhancement of the fourth metacarpophalangeal joint (white arrows). d Sagittal T1-weigthed image of the right elbow with fat suppression and after intravenous gadolinium administration demonstrates moderate effusion with synovial thickening and enhancement (black arrow). There is a ring-enhancing fluid collection (abscess) extending from the joint into the soft tissue antero-medially (white arrow)

Fig. 7

Several imaging findings in a male patient with deficiency of interleukin 1 receptor antagonist (DIRA). a Posteroanterior view of the mandible at the age of 7 years when he presented with left mandibular swelling shows a well-defined lytic lesion within the body of the left mandible with expansion of the bone and thinning of the cortex (arrow). There are no aggressive features. b Axial unenhanced CT of the chest in bone window demonstrates diffuse broadening of the ribs with ground glass density of the medulla and thinning of the cortex. Bone biopsy showed fibrous changes indicative of healing that is likely related to the patient’s bone disease. There are alveolar (black arrow) and interstitial (long white arrow) pulmonary opacities and nodules with cyst formation (short white arrow). Lung biopsy: pulmonary hemosiderosis. c Anteroposterior radiograph of the hands performed when the patient presented with abnormal nails demonstrates multiple bilateral symmetrical metaphyseal lytic lesions with associated cortical thinning (arrows). There is distal phalangeal soft tissue thickening

Fig. 8

A 14-year-old girl with HA20 presented with pain in her ankles and feet. a Anteroposterior radiograph of the right foot demonstrates joint space narrowing of the talonavicular and calcaneocuboid joints (arrows). Similar but asymmetrical changes are present in the left foot (not shown). b Lateral radiograph of the right ankle demonstrates subtalar joint space narrowing with subchondral sclerosis and subarticular cystic changes of the inferior surface of the talus (arrow). c Coronal STIR of the right ankle demonstrates fluid tracking along the tibialis posterior tendon (arrow) with post gadolinium enhancement (not shown). d Sagittal STIR and e T1-weighted image with fat suppression and intravenous gadolinium administration of the right ankle demonstrate subtalar joint space narrowing and subchondral cystic changes with surrounding edema involving the inferior articular surface of the talus and contrast enhancement (empty white arrow). There is joint space narrowing and small effusion in the tibiotalar, subtalar, and talonavicular joints with synovial contrast enhancement. There is retrocalceneal bursistis (white arrow). Arthritis, tenosynovitis, and retrocalceneal bursistis are likely inflammatory with degenerative changes of the subtalar joint

Fig. 9

A 5-week-old baby girl with bilious vomiting and abdominal distension. a–c Selected images of abdominal ultrasound demonstrate a marked gallbladder wall thickening and (b) small bowel wall thickening and hyperemia and (c) transverse colon wall thickening. There was lack of peristalsis on real time ultrasound and moderate ascites (not shown). There was no pneumatosis intestinalis. d Frontal fluoroscopic view of contrast enema performed at 8 weeks of life due to persistent abdominal distension and bloody diarrhea: the contrast is filling the colon, terminal ileum, and appendix: there is mildly reduced caliber of the colon with multiple areas of wall irregularities of the colon and terminal ileum. Note the massively dilated small bowel loops at the center of the abdomen. This patient is found to have IL-10 deficiency and positive genetic testing (IL10RB)

Fig. 10

A 12-year-old male with deficiency of adenosine deaminase type 2 (DADA2) and long history of recurrent fever, left thalamic stroke at 5 years of age, livedo reticularis, and erythema nodosum: a Axial T2-weighted image demonstrates high signal left thalamic lesion with mild negative mass effect (arrow), no surrounding edema and no diffusion restriction (not shown), indicative of old infarct. b Aortic angiogram through a right femoral puncture access: pruning, distal obliteration and irregularity of the intra-hepatic arteries (black arrow). There are multiple microaneurysms in the distal branches of the splenic artery (white arrows) and intra renal arteries of the right kidney (yellow arrows). There is hypervascularity of the jejunum with multiple irregularities and micro-aneurysms involving the jejunal branches (red arrows). Findings are in keeping with small vessel vasculitis such as polyarteritis nodosa (PAN). This patient tested positive for disease-causing gene mutation (CECR1)

Fig. 11

A 13-year-old girl with Aicardi-Goutieres syndrome. She has long history of arthritis, nodular rash, and chilblains started at the age of 2 years. Anteroposterior radiograph of the right hand demonstrates diffuse periarticular osteopenia, soft tissue swelling of the proximal interphalangeal joints (PIPs), mainly the third and fourth PIPs (arrows). There are no erosions, joint space narrowing or soft tissue calcifications. Similar changes are present in the left hand (not shown)

Fig. 12

Supine portable chest radiograph for a 15-month-old girl with sideroblastic anemia and immunodeficiency, periodic fever and developmental delay (SIFD), 1 month after bone marrow transplant: the radiograph demonstrates diffuse bilateral pulmonary opacities without cardiomegaly. Note the endotracheal tube and the right central venous line. The patient died with acute respiratory distress syndrome due to graft-versus-host disease