A child with Omenn syndrome
After presenting in the ED with failure to thrive and fever, the 7-week-old infant was diagnosed with pseudomonas meningitis and bacteremia. But less clear than the infection and bacteria in the blood was the scaly red appearance of her skin, an erythrodermic condition present since birth. Did she have a collodion membrane, a cellophane-like skin that typically sheds within 14 days of birth? Was the skin condition an ichthyosis like congenital ichthyosform erythroderma (CIE), or perhaps a severe combined immunodeficiency disease (SCID) like Omenn syndrome? Also, why did the child’s skin condition worsen with antibiotic treatment for the pseudomonas infection?
“Oddly, her erythroderma improved while she was sicker, and worsened when her infection was treated,” reported pediatric dermatology fellow Dakara Wright at a recent Hopkins Children’s case conference. “Was it related to a drug reaction?”
Most children who present with erythroderma don’t have collodion membrane, but CIE – the initial diagnosis – is a cause of erythroderma that can present at birth with a collodion membrane, added pediatric dermatologist Bernard Cohen: “I don’t know why but the skin lesions do tend to improve and disappear when they’re ill.”
Pediatric immunologist Howard Lederman was perplexed about another aspect of this case of a child with diffuse skin disease and pseudomonas meningitis. Pseudomonas, he noted, is not one of the usual pathogens seen in infants: “I really thought the most likely explanation for the pseudomonas infection were the breaks in the skin, which would make immunodeficiency disease less likely.”
Citing a Paris study of 51 cases of infantile erythroderma, Wright noted that the condition is very difficult to diagnose and treat, and often tied to an immune system malfunction. “On average, it took 11 months to come up with a diagnosis,” Wright said. The number one cause, she added, was immunodeficiency.
Immunodeficiencies with skin manifestations in the neonatal period, Wright explained, include SCID, Omenn syndrome, DiGeorge anomaly, and Wiskott-Aldrich syndrome. But the fact that the infant came into the world with these skin findings, said Lederman, made the case that much more confusing.
“With the exception of Wiskott-Aldrich, I don’t think I’ve ever seen an immunodeficient child born with these skin disorders,” said Lederman. “It doesn’t mean it can’t happen, but I don’t want to leave people with the impression that this is common.”
Unfortunately, before the team was able to get to the bottom of the case, the child developed thrombocytopenia – a low platelet count in the blood often caused by an immune system disorder – which can result in severe bleeding. Now, with the patient’s heart rate and blood pressure declining the team was concerned about the possibility of overwhelming sepsis.
Indeed, as the patient’s heart rate and blood pressure plummeted dramatically, she was diagnosed with cytomegalovirus (CMV), which worsened each day despite interventions with anti-virals. After 16 days in the hospital and discussions with the family, life support was withdrawn. Autopsy results showed CMV in the lung, liver and lymph node, but also eosinophilic infiltrates in the heart, pancreas and vertebral marrow, which suggested severe combined immunodeficiency disease. The skin and other laboratory abnormalities pointed to a specific type of SCID – Omenn syndrome. There was no evidence of an infection other than the overwhelming CMV.
“Everywhere we looked we ran into dead ends where the data didn’t fit together in any clean way, and we really weren’t sure what was going on with this child until the autopsy,” Lederman said. “It’s the most unfortunate part of the whole picture. If she didn’t have CMV, we might have been able to cure her disease with a bone marrow transplant.”