Congenital Diaphragmatic Hernia Patch Infection Presenting With Digital Clubbing

To the Editor, Here we present a case series of three children with a history of congenital diaphragmatic hernia (CDH) who developed infection of the surgical diaphragm patch years after repair, and whose sentinel presentation was digital clubbing. This study (IRB 21-018553) received a waiver of HIPAA authorization and was deemed exempt by the Institutional Review Board at the Children's Hospital of Philadelphia, as data collection was limited to retrospective chart review. Because the study involved secondary use of identifiable health information regulated by HIPPA, informed consent was not required. A 9-year-old female with a left-sided CDH status-post patch repair in the neonatal period was hospitalized due to several months of fatigue, 1 week of fevers, and erythematous digital clubbing (Figure 1A) that had not been present at her most recent outpatient evaluation. Her medical history also included Coffin-Siris Syndrome, very-early-onset inflammatory bowel disease, and specific antibody deficiency. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were markedly elevated (Supporting information Table S1). She underwent extensive evaluation to identify the cause of her symptoms, including imaging, laboratory testing, esophagogastroduodenoscopy, and colonoscopy. After these tests were unrevealing, magnetic resonance imaging (MRI) of the abdomen demonstrated extensive inflammatory changes and hyperenhancement surrounding the surgical mesh at the site of the CDH repair, concerning for a patch infection (Figure 2A,B). An exploratory laparotomy demonstrated that the patch was surrounded by foul-smelling fluid and extensive scar tissue. The patch was removed. A jejunal perforation was identified during the procedure, and the affected bowel segment was resected. Bacterial cultures of the patch grew Klebsiella variicola, Actinomyces turicensis, Pseudomonas aerigunosa, and Prevotella intermedia. She was treated with a 2-week course of antibiotics from the time of patch removal. At an outpatient visit 3 months later, the digital clubbing was markedly improved. A 4-year-old female with a left-sided CDH status post patch repair in the neonatal period and a history of urogenital sinus presented to an outpatient pulmonary visit with marked digital clubbing (Figure 1B) and vague, mild intermittent chest pain, with no other symptoms. Laboratory testing was notable for markedly elevated inflammatory markers (Supporting information Table S1) and anemia. CT scan of the chest and abdomen with contrast showed a moderate left pleural fluid collection with hyperenhancement and gas bubbles surrounding the surgical patch (Figure 2C,D). A mini thoracotomy revealed a large abscess surrounding the patch containing malodorous purulent fluid. The patch was removed, and a Jackson-Pratt (JP) drain was placed into the abscess cavity. The cultures of the patch and abscess grew Escherichia coli, Enterococcus faecalis, and Bacteroides fragilis. The JP drain remained in place for about 4 weeks. She received 8 weeks of antibiotics in total, and digital clubbing had resolved entirely at a follow-up visit 3 months after patch removal. A 4-year-old male with a left-sided CDH status post patch repair in the neonatal period presented to a routine outpatient visit with digital clubbing (Figure 1C) and no other significant symptoms. Inflammatory markers were elevated (Supporting information Table S1). CT scan and MRI of the chest and abdomen with contrast showed complex fluid with numerous gas bubbles surrounding the surgical patch, with left lower lobe consolidation and a small left pleural effusion (Figure 2C,D). An exploratory laparotomy identified extensive adhesions. Several loops of bowel were densely adherent to the spleen. Following lysis of adhesions, the patch was identified and removed, and a Blake drain was placed into the cavity. Culture of the patch grew Pseudomonas aeruginosa, Streptococcus mitis oralis, Ochrobactrum anthropi, and Candida parapsilosis. The patient experienced a complicated postoperative course including bowel injury and migration of the drain into the splenic flexure of the colon. He underwent multiple additional abdominal surgeries and received a prolonged course of parenteral nutrition and antibiotics. CDH is a highly morbid condition in which embryonic failure of diaphragm closure leads to herniation of abdominal contents into the thoracic cavity, resulting in pulmonary hypoplasia, pulmonary hypertension, and abnormal left ventricular structure and function. Reduction of abdominal viscera and closure of the diaphragm defect are often required during the first few weeks of life [1]. While smaller defects can be closed primarily with sutures, larger defects require placement of a synthetic Gore-Tex patch or muscle flap [2]. Use of a synthetic patch is associated with an increased risk of infection that can occur years after initial repair [3]. These infections are often polymicrobial, and may be associated with intestinal perforation or pneumonia [3]. Removal of the infected patch is mandatory. Following patch removal, further intervention (e.g., re-repair with muscle flap) depends on the degree of scar tissue present. In each of the three patients in our case series, the presence of extensive scar tissue sufficiently separated the thoracic and abdominal cavities, precluding the need for further diaphragm reconstruction. Patch infections can be challenging to diagnose. Authors from our institution recently published suggested criteria for suspected patch infection based on a case series of ten children with confirmed infections [3]. These criteria include clinical signs (fever, hypoxemia, respiratory distress, hypotension, flank edema), laboratory results suggestive of infection (elevated inflammatory markers, anemia, positive culture from normally sterile site), and imaging findings (fluid or gas collection between patch and lung base). To our knowledge, this case series is the first to describe digital clubbing as a manifestation of CDH surgical patch infection. Digital clubbing was first described by Hippocrates in the year 400 BCE in a patient with empyema [4]. It is seen in association with a variety of underlying cardiac, pulmonary, gastrointestinal, neoplastic, and infectious diseases [5]. While the underlying pathophysiology is incompletely understood, it is hypothesized to involve reduced fragmentation of megakaryocytes in the pulmonary circulation, release of proteins such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), angiogenesis, and local hypoxia [4]. Lung abscess, empyema, and inflammatory bowel disease are all well-described causes of digital clubbing; therefore, in patients with CDH and a surgical patch infection (and associated localized pulmonary/pleural and intestinal inflammation), it is understandable that digital clubbing can develop. Patients with CDH repaired with a surgical patch are at risk for developing a patch infection. Findings of a patch infection can be subtle, and digital clubbing may be one of the only abnormalities observed on physical examination. Clinicians should routinely examine the fingertips of all patients with a history of CDH and patch repair and obtain blood work (inflammatory markers) and advanced imaging if digital clubbing is present. Alexander I. Gipsman: conceptualization, writing – review and editing, writing – original draft, investigation, visualization. Mark N. Blanke: writing – review and editing. Edward R. Oliver: writing – review and editing, visualization. Holly L. Hedrick: writing –review and editing. Lisa M. Herkert: writing – review and editing. Howard B. Panitch: writing – review and editing, conceptualization, supervision. AIG is supported by NHLBI/NIH T32-HL160493. The authors have no conflicts of interest relevant to this article to disclose. The data that support the findings of this study are available from the corresponding author upon reasonable request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.