A severe course of serogroup W meningococcemia in a patient with infantile nephropathic cystinosis

ABSTRACT

We present a 9-month old boy with cystinosis admitted to our hospital with the complaints of vomiting, diarrhea and seizure. While he was hospitalized in a pediatric intensive care unit due to worsening of his signs related to cystinosis, within hours, he suffered complications of septic shock, acute renal failure, and disseminated intravascular coagulation, due to invasive Neisseria meningitidis serogroup W disease. Our patient is the first reported case of invasive meningococcal disease with cystinosis. Clinicians should consider that the unexpected and serious clinical findings of invasive meningococcal disease can mimic and/or masquerade as other metabolic diseases. Vaccination strategies, according to serogroup epidemiology and age distribution, should be implemented for the prevention of meningococcal infections.

Invasive meningococcal disease (IMD) results from infection with Neisseria meningitidis (N. meningitidis) and is associated with long-term sequelae and high case-fatality rates. The incidence of IMD is highest among children (especially infants). In addition to age, other risk factors include functional or anatomic asplenia, congenital complement deficiency and human immunodeficiency virus, taking eculizumab for paroxysmal nocturnal hemoglobinuria or atypical hemolytic uremic syndrome, being a laboratory worker, and attending mass gatherings.¹ Recently, Booy et al.² highlighted an increased rate of serogroup W IMD and/or the proportion of all IMD cases due to serogroup W (MenW) in Chile, Australia, United Kingdom and the Netherlands. The diversity and virulence of Men W strain variants have different clinical presentations, and which may result in increased mortality.^2,3 Since 2005, Men W is one of the leading causes of bacterial meningitis and IMD among children.^4-6 Cystinosis, which is an autosomal recessive metabolic disease that is caused by mutations in the CTNS gene (located on the short arm of chromosome17), also causes dysfunction in the kidneys, corneas, bone marrow, thyroid, lymph nodes, liver, and spleen. Infantile nephropathic cystinosis (INC) is the most common and severe form of cystinosis.⁷ To the best of our knowledge, there have been no reported cases of IMD among patients with cystinosis.

A nine-month-old boy who had been followed with a diagnosis of INC since five months of age was admitted with complaints from the parents of vomiting, diarrhea and seizure. Sixteen hours before his admission when at a routine medical visit, his physical examination and laboratory tests were within normal limits. He suffered vomiting and diarrhea within hours but did not receive his routine medications at that time. He was brought to the hospital by ambulance with generalized tonic seizures. At admission, his general condition was poor: he had tachypnea, tachycardia, an arterial blood pressure of 81/56 mmHg, a capillary refill time of 4 seconds, and a Glasgow Coma Score of 7. He was treated with intravenous glucose and calcium due to hypoglycemia and hypocalcemia and given a midazolam infusion. He was intubated, transferred to the intensive care unit, and immediately started on cefotaxime. Within two hours, the patient had hypotension, and his laboratory results showed anemia, thrombocytopenia, acute renal failure, and disseminated intravascular coagulation. The patient had hypotension despite inotrope infusion and had spontaneous rectal bleeding. Teicoplanin and polyclonal IgM-enriched intravenous IgG were administred. Because of his severe and sudden clinical course, we suspected IMD and serum RT-PCR showed MenW. On Day 5 of hospitalization, the clinical findings of infection regressed; however, the patient had severe neurological deficits. A cranial MRI examination showed several findings, which were interpreted as bleeding, edema, hypoxia secondary to meningococcemia, and delay in myelination secondary to metabolic disease. Antibiotic treatments were ceased on Day 10. We have continued to follow the patient in our outpatient clinic for INC with severe neurological sequelae.

Cystinosis requires continuous electrolyte replacement due to intense electrolyte loss, seizure, and shock.⁷ IMD due to Men W, mainly new hypervirulent CC11 clones, might be present with gastrointestinal symptoms, such as vomiting and diarrhea as in this report.³ In Turkey, an early period of surveillance study, which started in 2005, highlights the emergence of MenW strains which were closely related to the strain responsible for the MenW Hajj epidemic.⁴ Thereafter, MenW has been one of the leading cause of IMD along with MenB.⁵ MenW is also the main serogroup for meningococcal carriage among adolescents and young adults.⁸ Our patient was the first reported case of IMD and cystinosis, and we found neither a risk association nor a pathophysiological explanation for this diagnosis. Clinicians should consider that the unexpected and serious clinical findings of IMD can mimic and/or masquerade as other metabolic diseases. Vaccination strategies, according to serogroup epidemiology and age distribution, should be implemented for the prevention of IMD.¹

Funding Statement

EC Dinleyici has received grants to support research projects and consultancy fees from GSK, Pfizer and Sanofi Pasteur

Disclosure of potential conflicts of interest

EC Dinleyici has received grants to support research projects and consultancy fees from GSK, Pfizer and Sanofi Pasteur. Other authors declares no conflict of interest.