Correspondence

Case 19-2007: A College Student with Fever and Joint Pain

N Engl J Med 2007; 357:1779-1780October 25, 2007

Article

To the Editor:

In the Case Record of a patient with infectious mononucleosis and disseminated gonococcal disease with septic arthritis (June 21 issue),1 Dr. Davis does not consider, among the possible diagnoses, inflammatory bowel disease. This possibility should always be given serious consideration in a young adult who presents with pauciarticular arthritis associated with lower abdominal pain, anemia, fever, nausea, and vomiting. Extraintestinal manifestations of inflammatory bowel disease are observed in approximately 25 to 35% of patients.2 More specifically, a peripheral form of arthritis is noted in 10% of patients.2 This arthritis typically affects larger joints and, in some cases, can be the first presenting symptom. Furthermore, the patient described in the case had oral aphthous ulcers, a relatively common clinical manifestation in patients with Crohn's disease.3

Ruggero Spadafora, M.D.
University of California at San Francisco, San Francisco, CA 94143
ruggero.spadafora@ucsf.edu

3 References

1. 1

   Case Records of the Massachusetts General Hospital (Case 19-2007). N Engl J Med 2007;356:2631-2637
   Full Text | Web of Science | Medline

2. 2

   Hyams JS. Inflammatory bowel disease. Pediatr Rev 2005;26:314-320
   CrossRef | Web of Science | Medline

3. 3

   Weinstein TA, Sciubba JJ, Levine J. Thalidomide for the treatment of oral aphthous ulcers in Crohn's disease. J Pediatr Gastroenterol Nutr 1999;28:214-216
   CrossRef | Web of Science | Medline

To the Editor:

Davis and Pasternack report a final diagnosis of meningococcal arthritis and coincidental infectious mononucleosis associated with the Epstein–Barr virus (EBV). The diagnosis was somewhat unexpected, because the patient had in fact been vaccinated against meningococcus (Neisseria meningitidis), and indeed, the working diagnosis was gonococcal arthritis (from N. gonorrhoeae infection), despite the patient's history of consistent condom use with a single sexual partner. We suggest that the EBV-associated mononucleosis is not coincidental to the patient's meningococcal arthritis, but in fact permissive for it. From the given history, the patient had signs, symptoms, and results of laboratory tests that were consistent with EBV-associated infectious mononucleosis approximately 8 days before there were any signs or symptoms of meningococcal infection. EBV can be immunosuppressive, and we think this may have allowed the meningococcus to break through the vaccine-induced immunity. Furthermore, the patient was given high-dose prednisone 2 days before presenting with meningococcemia. This medicine too may have been immunosuppressive.

Eric Altschuler, M.D., Ph.D.
Alice Hon, B.S.
Abigail Huang, B.S.
New Jersey Medical School, Newark, NJ 07103
eric.altschuler@umdnj.edu

To the Editor:

Pasternack states that available vaccines do not include group B antigens and do not cover group B meningococcal strains because of homology between the group B polysaccharide and human neural glycolipid antigens. The antimeningococcal vaccine BC of the Finlay Institute, Vamengoc BC, is based on purified outer-membrane proteins and lipids from selected group B meningococcal strains, assembled as proteoliposomes, and coformulated with group C polysaccharide, resulting in a very stable and consistent bivalent BC vaccine.1,2 Vamengoc BC does not contain group B polysaccharide. The protective immune response is based on specific antibodies to proteins and lipopolysaccharide, with opsonic and bactericidal activity with a predominant type 1 helper T cell cytokine pattern.3,4 This vaccine was licensed in Cuba in 1989 and was widely used there to control an epidemic. It is now included in the National Immunization Schedule. Nearly 60 million doses administered in Cuba and elsewhere and 20 years of experience with this vaccine have certified its efficacy and safety.

Beatriz Tamargo Santos, M.Sc.
Instituto de Farmacia y Alimentos, 16017 Havana, Cuba
btamargos@gmail.com

Gustavo Sierra Gonzalez, M.D., Ph.D.
Finlay Institute, 16017 Havana, Cuba

Dr. Sierra Gonzalez reports coauthoring the fundamental patents covering vaccine rights to the Vamengoc BC vaccine and reports being the founder of the Finlay Institute.

4 References

1. 1

   Sierra GV, Campa HC, Varcacel NM, et al. Vaccine against group B Neisseria meningitidis: protection trial and mass vaccination results in Cuba. NIPH Ann 1991;14:195-210
   Medline

2. 2

   Perez O, Lastre M, Lapinet J, et al. Immune response induction and new effector mechanisms possibly involved in protection conferred by the Cuban anti-meningococcal BC vaccine. Infect Immun 2001;69:4502-4508
   CrossRef | Web of Science | Medline

3. 3

   Galguera M, Sierra G, Martinez E, et al. Utilización terapéutica de gammaglobulina hiperinmune específica en la enfermedad meningocócica del niño. Rev Cubana Pediatr 1991;63:55-62
   

4. 4

   Uli L, Castellanos-Serra L, Betancourt L, et al. Outer membrane vesicles of the VA-MENGOC-BC vaccine against serogroup B of Neisseria meningitidis: analysis of protein components by two-dimensional gel electrophoresis and mass spectrometry. Proteomics 2006;6:3389-3399
   CrossRef | Web of Science | Medline

Author/Editor Response

Sierra Gonzalez and colleagues pioneered the development of outer-membrane protein–based vaccines, rather than polysaccharide vaccines, against serogroup B N. meningitidis nearly 20 years ago. The safety and efficacy of this general approach are being replicated in Europe and New Zealand.1 Unfortunately, space limitations in the Discussion section precluded a systematic review of vaccine-development strategies against serogroup B disease. Isolates of serogroup B outer-membrane proteins have considerable temporal and geographic variation, and polyvalent outer-membrane protein–based vaccines will probably be necessary to provide reasonably broad protection against the antigenically diverse serogroup B meningococcal strains circulating in different countries.1

Mark S. Pasternack, M.D.
Massachusetts General Hospital, Boston, MA 02114

1 References

1. 1

   Trotter CL, Ramsay ME. Vaccination against meningococcal disease in Europe: review and recommendations for the use of conjugate vaccines. FEMS Microbiol Rev 2007;31:101-107
   CrossRef | Web of Science | Medline