This was put together in 1998 so it's a bit out of date, but
it seems relevant. Note the large number of studies in the
"Central Nervous System DeMYELINation" section. Interesting
that at this time the links to arthritis were mostly case
reports. Funny how "anecdotal" evidence is still evidence. -Dave

Abstracts on Hepatitis B Vaccine

Dave Foster : 1-12-98

    I. Overview
   II. Central Nervous System Demyelination, Myelitis and Inflammation
  III. Various Adverse Reactions: Mostly Case Reports


J Fam Pract 1997 Oct;45(4):295-315; quiz 317-8

Published erratum appears in J Fam Pract 1997 Dec;45(6):464

Hepatitis B virus infection, hepatitis B vaccine, and hepatitis B immune

Zimmerman RK, Ruben FL, Ahwesh ER

Department of Family Medicine and Clinical Epidemiology, University of
Pittsburgh School of Medicine, USA.

Hepatitis B virus (HBV) infection is a major health problem in the United
States; in 1995, approximately 128,000 cases occurred. Transmission of HBV
occurs primarily by blood exchange (eg, by shared needles during injection
drug use) and by sexual contact. Persons infected early in life are much
more likely to become chronically infected than those infected during
adulthood: as many as 90% of infants infected perinatally develop chronic
infection and up to 25% will die of HBV-related chronic liver disease as
adults. Clinical signs of acute hepatitis occur in about 50% of infected
adults but in only 5% of infected preschool-aged children. In the United
States, hepatitis B vaccine is currently made by recombinant DNA technology
using baker's yeast. Preexposure vaccination results in protective antibody
levels in almost all infants and children (> 95%) and healthy adults younger
than 40 years of age (> 90%). The most common adverse event following
administration of hepatitis B vaccine is pain at the injection site, which
occurs in 13% to 29% of adult and 3% to 9% of children. A comprehensive
hepatitis B vaccination policy is now recommended that includes (1) routine
infant vaccination; (2) catch-up vaccination of 11- to 12-year-olds who were
not previously vaccinated; (3) catch-up vaccination of young children at
high risk for infection; (4) vaccination of adolescents and adults based on
lifestyle or environmental, medical, and occupational situations that place
them at risk; and (5) prevention of perinatal HBV infection.

PMID: 9343051, UI: 98002568

Vaccine 1998 Feb;16(4):329-34

Major adverse reactions to yeast-derived hepatitis B vaccines--a review.

Grotto I, Mandel Y, Ephros M, Ashkenazi I, Shemer J

Israel Defense Force, Medical Corps, Israel.

Yeast-derived recombinant DNA hepatitis B vaccines usage became widely
accepted since the early 1990s. Severe adverse events have been reported
infrequently in adults and rarely in infants and children given hepatitis B
vaccine in the ten years which have passed since the introduction of the
vaccine. Some of the data were summarized in previous review articles. Our
review of the literature revealed reports of serious adverse reactions which
included immediate reactions (anaphylaxis and urticaria) as well as delayed
reactions, including skin, rheumatic, vasculitic (including Systemic Lupus
Erythematosus and glumerulonephritis), hematologic, ophthalmologic and
neurologic reactions. These cases were summarized and a pathogenetic
mechanism is offered.

PMID: 9607051, UI: 98269934

Science 1998 Jul 31;281(5377):630-1

A shadow falls on hepatitis B vaccination effort.

Marshall E

PMID: 9714670, UI: 98370231

Lakartidningen 1996 Mar 6;93(10):883

[General vaccination against hepatitis B is not justified].

[Article in Swedish]

Oberg S

Infektionskliniken, Uddevalla sjukhus.

PMID: 8656789, UI: 96248664

Can Commun Dis Rep 1992 Apr 17;18(7):49-53

Adverse events following the administration of hepatitis B vaccines.

Bentsi-Enchill A

University of Ottawa.

PMID: 1291014, UI: 93177423

Vaccine 1993 Oct;11(13):1358-9

Serious hepatitis B vaccine adverse reactions, are they immune-mediated?

Carmeli Y, De-Medina T

Publication Types:

   * Letter

PMID: 8296488, UI: 94127088

II. Central Nervous System Demyelination, Myelitis and Inflammation

Postgrad Med J 1997 Jul;73(861):462-3

Hepatitis B vaccine and neurotoxicity.

Pirmohamed M, Winstanley P

CSM Mersey Regional Monitoring Centre, Pharmacy Practice Unit, Liverpool,

PMID: 9338045, UI: 97479393

Lancet 1991 Nov 9;338(8776):1174-5

Central-nervous-system demyelination after immunisation with recombinant
hepatitis B vaccine.

Herroelen L, de Keyser J, Ebinger G

Department of Neurology, University Hospital, Free University of Brussels,

2 patients had neurological symptoms and signs, with evidence of
central-nervous-system demyelination, 6 weeks after administration of
recombinant hepatitis B vaccine. 1 had known multiple sclerosis but the
other had no history of neurological disease; both had HLA haplotypes DR2
and B7, which are associated with multiple sclerosis. A causal link between
vaccination and demyelination cannot be established from these 2
case-reports, but the time interval would fit a proposed immunological


   * Comment in: Lancet 1992 Jan 18;339(8786):178-9

PMID: 1682594, UI: 92047879

J Neurol Neurosurg Psychiatry 1995 Jun;58(6):758-9

Central nervous system demyelination after vaccination against hepatitis B
and HLA haplotype.

Kaplanski G, Retornaz F, Durand J, Soubeyrand J

Publication Types:

   * Letter

PMID: 7608688, UI: 95332874

Neurology 1978 Sep;28(9 Pt 2):111-4

Viral models of demyelination.

Weiner LP, Stohlman SA

PMID: 568744, UI: 79053490

AJNR Am J Neuroradiol 1995 Mar;16(3):581-2

MR imaging in a case of postvaccination myelitis.

Tartaglino LM, Heiman-Patterson T, Friedman DP, Flanders AE

Department of Radiology, Jefferson Medical College, Philadelphia, Pa. 19107,

We describe a case of acute transverse myelitis after the administration of
the recombinant form of hepatitis B vaccine. Abnormal enhancement of MR
imaging accompanied residual neurologic deficit.

PMID: 7793384, UI: 95313683

Presse Med 1993 Dec 18;22(40):1997-8

[Acute myelitis after vaccination against hepatitis B].

[Article in French]

Mahassin F, Algayres JP, Valmary J, Bili H, Coutant G, Bequet D, Daly JP

Service de Clinique medicale, Hopital d'Instruction des Armees du
Val-de-Grace, Paris.

A 56-year old man was hospitalized for spasmodic paraparesis with sphincter
disorders. After exclusion of spinal cord compression and all other
inflammatory, infectious or neoplastic causes, the possibility of a
connexion with an hepatitis B vaccination performed with a recumbent vaccine
three weeks before the neurological disorders appeared was considered. The
pathogenesis of such a myelitis remains uncertain. It is based on the
possible reactivation of a dormant virus or a crossed antigenic reaction
between a protein of the vaccine and the nervous system. The course of the
disease is usually favourable. The frequency of this complication would be
more accurately determined if all neurological manifestations occurring
after hepatitis B vaccination were reported.

PMID: 8127802, UI: 94173824

J Korean Med Sci 1997 Jun;12(3):249-51

Acute Myelitis after hepatitis B vaccination.

Song HK, Kim HC, Yun YH

Department of Neurology, Hallym University Medical College, Kangdong Sacred
Heart Hospital, Seoul, Korea.

We report a case of myelitis after plasma-derived hepatitis B vaccination.
The patient was a 31-year-old man who presented with progressive sensory
symptoms in extremities that developed 2 weeks after a third vaccination.
MRI of the cervicothoracic region revealed swelling and T2 high signal at
the level of C4 to C5 cord, and isolated enhancement in the posterior
columns between C4 and C5 cord. The significance of MRI findings and HLA
haplotype of the patient will be briefly discussed.

PMID: 9250923, UI: 97394595

Gastroenterol Clin Biol 1996;20(4):401-2

[Acute myelitis after immunization against hepatitis B with recombinant

[Article in French]

Senejoux A, Roulot D, Belin C, Tsakiris L, Rautureau J, Coste T

Publication Types:

   * Letter

PMID: 8758508, UI: 96332745

J Hepatol 1993 Sep;19(2):317-8

Transverse myelitis following hepatitis B vaccination.

Trevisani F, Gattinara GC, Caraceni P, Bernardi M, Albertoni F, D'Alessandro
R, Elia L, Gasbarrini G

Publication Types:

   * Letter

PMID: 8301068, UI: 94132548

Presse Med 1997 Mar 8;26(7):328

[Acute aseptic meningitis after hepatitis B vaccination].

[Article in French]

Heinzlef O, Moguilewski A, Roullet E

Publication Types:

   * Letter

PMID: 9122145, UI: 97252911

Presse Med 1996 Oct 26;25(32):1561-2

[Meningeal reaction after vaccination against hepatitis B].

[Article in French]

Marsaudon E, Barrault MF

Publication Types:

   * Letter

PMID: 8952667, UI: 97110516

Am J Ophthalmol 1996 Sep;122(3):431-2

Multiple evanescent white dot syndrome after hepatitis B vaccine.

Baglivo E, Safran AB, Borruat FX

Department of Ophthalmology, Geneva University Hospital, Switzerland.

PURPOSE: Hepatitis B vaccine has become an effective means of preventing
complications of hepatitis B. However, it occasionally induces serious side
effects. We report a case of multiple evanescent white dot syndrome (MEWDS)
that occurred following hepatitis B vaccination. METHODS: A 23-year-old
woman with a one-week history of progressive loss of vision in the left eye
and bilateral photopsia was referred for examination. Her symptoms appeared
24 hours after a booster intramuscular injection of hepatitis B vaccine.
RESULTS: Clinical examination, fluorescein angiography, and the course of
events were typical of MEWDS. CONCLUSIONS: This case demonstrates the
occasional occurrence of MEWDS after hepatitis B vaccine and suggests that
hepatitis B virus immunization may be a risk factor for this retinal

PMID: 8794720, UI: 96387180

Ann N Y Acad Sci 1997 Dec 29;830:319-21

Sudden hearing loss in childhood consequent to hepatitis B vaccination: a
case report.

Orlando MP, Masieri S, Pascarella MA, Ciofalo A, Filiaci F

ENT Clinic, University La Sapienza, Rome, Italy.

PMID: 9616691, UI: 98279663

Clin Infect Dis 1993 Nov;17(5):928-9

Multiple sclerosis and hepatitis B vaccination.

Nadler JP

Publication Types:

   * Letter

PMID: 8286645, UI: 94114816

Acta Neurol Scand 1994 Jun;89(6):462-3

Acute cerebellar ataxia after immunisation with recombinant hepatitis B

Deisenhammer F, Pohl P, Bosch S, Schmidauer C

Department of Neurology, University of Innsbruck, Austria.

We report one woman with acute cerebellar ataxia (ACA), a well-defined
clinical syndrome, which occurred 10 days after the second vaccination with
recombinant hepatitis B vaccine. The patient had no previous symptoms or
signs of neurological disease and there was no evidence of neurologic
disease in the family history. Within nine months the symptoms remitted
completely according to other reports of ACA. As there was a close temporal
connection and no noticeable other cause we assume a causal link between the
vaccination and the disease. As far as we know this is the first case of
ACA after hepatitis B vaccination.

PMID: 7976236, UI: 95066735

Lancet 1993 Aug 28;342(8870):563-4

Visual loss and eosinophilia after recombinant hepatitis B vaccine.

Brezin A, Lautier-Frau M, Hamedani M, Rogeaux O, Hoang PL

Publication Types:

   * Letter


   * Comment in: Lancet 1993 Oct 16;342(8877):998

PMID: 8102709, UI: 93360669

J Hepatol 1996 Jun;24(6):764-5

Leukoencephalitis after recombinant hepatitis B vaccine.

Manna R, De Santis A, Oliviero A, Carnevale A, Caputo S, Pahor M, Laudisio
A, Gasbarrini G

Publication Types:

   * Letter

PMID: 8835755, UI: 96432703

III. Various Adverse Reactions: Mostly Case Reports

Arch Dis Child 1998 Mar;78(3):273-4

Thrombocytopenic purpura as adverse reaction to recombinant hepatitis B

Ronchi F, Cecchi P, Falcioni F, Marsciani A, Minak G, Muratori G, Tazzari
PL, Beverini S

Divisione Pediatrica-Ospedale Civile di Cattolica (RN), Cattolica (RN),

Three cases of immune thrombocytopenic purpura after the first dose of
recombinant hepatitis B vaccine occurred in infants under 6 months of age.
Other possible causes of this condition were excluded. Antiplatelet
antibodies were present. A defect in platelet production was excluded in two
children. Corticosteroid treatment was effective. Subsequent administration
of other vaccines (against polio, diphtheria, and tetanus) did not cause
relapse of thrombocytopenia.

PMID: 9613364, UI: 98276312

Eur J Dermatol 1998 Sep;8(6):435-6

Generalized granuloma annulare and hepatitis B vaccination.

Wolf F, Grezard P, Berard F, Clavel G, Perrot H

Dermatology Department, Hopital de l'Antiquaille, rue de l'Antiquaille,
69321 Lyon Cedex 05, France.

As hepatitis B vaccination is becoming generalized in Europe, cutaneous
adverse events are being more frequently reported in the literature. We
report the first case of generalized granuloma annulare following hepatitis
B immunization. A 51-year-old woman presented a generalized granuloma
annulare one month after the one-year booster injection of the hepatitis B
vaccine. The lesions resolved with sulfone therapy. We observed an identical
recurrence three weeks after the five-year booster.

PMID: 9729059, UI: 98398549

Lancet 1994 Nov 5;344(8932):1292-3

Liver dysfunction and DNA antibodies after hepatitis B vaccination.

Lilic D, Ghosh SK

Publication Types:

   * Letter

PMID: 7967997, UI: 95057572

BMJ 1994 Dec 3;309(6967):1513

Reiter's syndrome attributed to hepatitis B immunisation.

Fraser PA, Wilson JD

Publication Types:

   * Comment
   * Letter


   * Comment on: BMJ 1994 Jul 9;309(6947):94

PMID: 7804068, UI: 95102375

Pediatr Dermatol 1994 Dec;11(4):363-4

Erythema multiforme following hepatitis B vaccine.

Di Lernia V, Lo Scocco G, Bisighini G

Publication Types:

   * Letter

PMID: 7899194, UI: 95207066

Presse Med 1993 Feb 20;22(6):269

[Benign acute pericarditis after vaccination against hepatitis B].

[Article in French]

Bensaid J, Denis F

Publication Types:

   * Letter

PMID: 8511146, UI: 93288675

N Engl J Med 1996 Aug 1;335(5):355

Cryoglobulinemia after hepatitis B vaccination.

Mathieu E, Fain O, Krivitzky A

Publication Types:

   * Letter

PMID: 8668224, UI: 96283165

Presse Med 1997 Feb 1;26(2):75

[Erosive polyarthritis triggered by vaccination against hepatitis B].

[Article in French]

Soubrier M, Dubost JJ, Bielsa C, Ristori JM, Bussiere JL

Publication Types:

   * Letter

PMID: 9082414, UI: 97226581

Med J Aust 1996 Feb 5;164(3):187

Hepatitis B surface antigenaemia in a child after vaccination.

Dickie AS, Olszewski EH

Publication Types:

   * Letter


   * Comment in: Med J Aust 1996 Apr 15;164(8):510

PMID: 8628142, UI: 96205691

Lancet 1993 Oct 16;342(8877):998

Eosinophilia after intradermal hepatitis B vaccination.

Nagafuchi S, Tokiyama K, Kashiwagi S, Yayashi S, Imayama S, Niho Y

Publication Types:

   * Comment
   * Letter


   * Comment on: Lancet 1993 Aug 28;342(8870):563-4

PMID: 8105253, UI: 94018194

Ann Dermatol Venereol 1996;123(10):657-9

[Cutaneous lupus erythematosus and buccal aphthosis after hepatitis B
vaccination in a 6-year-old child].

[Article in French]

Grezard P, Chefai M, Philippot V, Perrot H, Faisant M

Service de Dermatologie, Hopital de l'Hotel-Dieu, Lyon.

INTRODUCTION: Although the hepatitis B vaccination tolerance is generally
good, adverse effects, which are specially neurologic and cutaneous, have
been observed and some cases of induced diseases with immunological
disorders have been reported. CASE REPORT: A 6 year-old boy presented a
cutaneous lupus erythematosus and a severe buccal aphthosis following
hepatitis B vaccination. There was no clinical or biological symptom of
systemic lupus erythematosus nor of Behcet's disease. Under chloroquine
therapy, the cutaneous manifestations of lupus erythematosus disappeared
quickly and those of buccal aphthosis improved. DISCUSSION: Hepatitis B
vaccination side effects are probably in relation with a specific or non
specific stimulation of the immune system. In our case, cellular immunity is
perhaps involved through the HBs antigen. Considering the rarity of these
side effects, an individual predisposition seems very likely.

PMID: 9615128, UI: 98277333

Arch Dermatol 1994 Oct;130(10):1329-30

Lichen planus following hepatitis B vaccination.

Aubin F, Angonin R, Humbert P, Agache P

Publication Types:

   * Letter

PMID: 7944523, UI: 95031207

Am J Med 1995 Jun;98(6):595-6

A case of severe cytolysis after hepatitis B vaccination.

Germanaud J, Causse X, Trinh DH, Pfau-Fandard B, Trepo C

Publication Types:

   * Comment
   * Letter


   * Comment on: Am J Med 1992 Mar;92(3):254-6

PMID: 7778577, UI: 95297482

Presse Med 1996 Sep 28;25(28):1301

[Bilateral neuro-papillitis after hepatitis B vaccination].

[Article in French]

Berkman N, Benzarti T, Dhaoui R, Mouly P

Publication Types:

   * Letter

PMID: 8949792, UI: 97107044

Rev Med Interne 1997;18(6):491-2

[Is hepatitis B vaccination a new cause of necrotizing vasculitis]?

[Article in French]

Kerleau JM, Levesque H, Lair G, Lecomte F, Carrara O, Courtois H

Publication Types:

   * Letter

PMID: 9247052, UI: 97390000

Ann Rheum Dis 1998 Apr;57(4):256-7

A case of Churg-Strauss vasculitis after hepatitis B vaccination.

Vanoli M, Gambini D, Scorza R

Publication Types:

   * Letter

PMID: 9709187, UI: 98374849

Presse Med 1997 Apr 26;26(14):670

[A case of segmentary unilateral occlusion of the central retinal vein
following hepatitis B vaccination].

[Article in French]

Berkman N

Publication Types:

   * Letter

PMID: 9180888, UI: 97324783

Lancet 1996 Jun 8;347(9015):1626

Occlusion of central retinal vein after hepatitis B vaccination.

Devin F, Roques G, Disdier P, Rodor F, Weiller PJ

Publication Types:

   * Letter

PMID: 8667894, UI: 96240964

Presse Med 1998 Jun 6;27(20):965-6

[Hypersensitivity vasculitis after hepatitis B vaccination].

[Article in French]

Masse I, Descoffres MC

Publication Types:

   * Letter

PMID: 9767839, UI: 98440953

Thorax 1993 May;48(5):580-1

Pulmonary and cutaneous vasculitis following hepatitis B vaccination.

Allen MB, Cockwell P, Page RL

St James's University Hospital, Leeds.

PMID: 8322254, UI: 93310736

Endocr J 1998 Feb;45(1):135

Subacute thyroiditis after hepatitis B vaccination.

Toft J, Larsen S, Toft H

PMID: 9625459, UI: 98287141

Br J Rheumatol 1994 Oct;33(10):991

Acute sero-positive rheumatoid arthritis occurring after hepatitis

Vautier G, Carty JE

Publication Types:

   * Letter

Scand J Rheumatol 1995;24(1):50-2

Arthritis after hepatitis B vaccination. Report of three cases.

Gross K, Combe C, Kruger K, Schattenkirchner M

Rheumatology Unit, LM University of Munich, Germany.

Side effects of hepatitis vaccination are rare. Only a few cases of
arthritis after hepatitis vaccination have been published. We report on
three cases of vaccination-induced arthritis with different resulting
disease. Two cases show the pattern of reactive arthritis. None of them was
associated with HLA-B27. In the third case onset of rheumatoid arthritis was
triggered by hepatitis vaccination. These three cases show that arthritis
after hepatitis B vaccination probably is more common than reported so far,
especially in a genetically predisposed subject (two of our patients
expressed HLA-DR4).

PMID: 7863281, UI: 95167436

Br J Rheumatol 1997 Feb;36(2):300-1

Polyarthritis associated with hepatitis B vaccination.

Bracci M, Zoppini A

Publication Types:

   * Letter

PMID: 9133957, UI: 97279516

Clin Nephrol 1995 May;43(5):349

Nephrotic syndrome after recombinant hepatitis B vaccine.

Macario F, Freitas L, Correia J, Campos M, Marques A

Publication Types:

   * Letter

PMID: 7634556, UI: 95361242

Clin Infect Dis 1992 Dec;15(6):1051

Evans's syndrome triggered by recombinant hepatitis B vaccine.

Martinez E, Domingo P

Publication Types:

   * Letter

PMID: 1457642, UI: 93091042

   << All opinions expressed are mine, not the University's >>

   David Foster    National Center for Microscopy and Imaging Research
    Programmer/Analyst     University of California, San Diego        Department of Neuroscience, Mail 0608
    (858) 534-7968

   "The reasonable man adapts himself to the world; the unreasonable one
   persists in trying to adapt the world to himself.  Therefore, all progress
   depends on the unreasonable."   -- George Bernard Shaw