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An unexpected trismus
Case Report
An unexpected trismus Mikael Alves, Etienne Canoui, Lionel Deforges, Laurent Garderet, Bertrand Guidet, Georges Offenstadt, Eric Maury
In September, 2011, an 86-year-old woman was admitted to our medical intensive care unit with trismus and neck stiffness. 2 years earlier, she had been diagnosed with marginal zone lymphoma. Her medications included chlorambucil from January to October, 2010, followed by rituximab, cyclophosphamide, vincristine, and prednisone in March, 2011. Prednisone (20 mg per day) was maintained from March to August, 2011. 5 months before presentation, she had several falls and she received local care with 3 stitches for a chin wound in April 2011, and was given a first tetanus vaccination. She had not previously been vaccinated for tetanus and complete vaccination was proposed, but she refused. In August, 2011, she had another fall, resulting in a severe wound to her left leg. She was given oral amoxicillin clavulanate and daily wound care for a week. She reported 10 days afterwards, dysphagia, gait instability, dysarthria, stiffness of the neck, and intractable trismus. She was referred the same day to our hospital. On presentation, she was alert and fully oriented. Core temperature was 37°C. She was severely malnourished. Her weight was 42 kg, for a height of 152 cm, and she had diffuse muscle atrophy, skin fragility, and splenomegaly. The left calf wound was dry and clean. There was no limb weakness. Plantar responses were normal. Trismus with stiffness of the neck after a wound suggested tetanus. We aimed to rule out meningitis because of her underlying immunosuppression. CSF was normal and cultures remained negative. Tetanus antitoxin (500 IU) and tetanus vaccine (40 IU) were given. Mechanical ventilation and intravenous sedation were initiated.
Lancet 2012; 380: 536 Medical Intensive Care Unit (M Alves MD, E Canoui MD, Prof B Guidet MD, Prof G Offenstadt MD, Prof E Maury MD), Department of Haematology (L Garderet MD), and Inserm UMR S707 (Prof B Guidet, Prof G Offenstadt, Prof E Maury), Hospital Saint-Antoine, Paris, France; and Department of Bacteriology Hospital Henri Mondor, Creteil, France (L Deforges MD) Correspondence to: Dr Mikael Alves, Medical Intensive Care Unit, Hospital Saint-Antoine, 184 Rue du Fauborg Saint Antoine, Paris 75571, France [email protected]
Efficient protection, repeat antibody titre after 10 years
Tetanus antibodies titres
5 Efficient protection, repeat antibody titre within 5 to 10 years
Contributors MA, EC, LG, BG, GO, LD, and EM looked after the patient. MA, BG, GO, and EM wrote the report. Written consent to publication was obtained.
1 Efficient protection, repeat antibody titre after 2 years 0·5 Low protection, booster recommended 0·1
1 19 ,2
01 pe at Re
ta pe a Re
ab
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re
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01
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ac
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e: S
Ap
ep t2
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01 1
01 1
Detection threshold, no protection
Month, year
Figure: Vaccination record of our patient and international recommendations according to tetanus antibody titres
536
Because of continuing spasms, intrathecal baclofen (1200 μg per day) was started on day 3 with a good clinical response. It was stopped on day 8 because Pseudomonas aeruginosa meningitis was diagnosed; it resolved favourably with removal of the intrathecal catheter and intravenous ceftazidime. She experienced ventilator-associated pneumonia and was finally transferred to the rehabilitation ward on day 46. No antibodies to tetanus toxin were detected, by the tetanus ELISA IgG TestKit (Virotech, InGen, Chilly-Mazarin, France), on admission, or 30 days after each of three subsequent tetanus toxoid vaccinations. On day 58 after discharge from the intensive care unit, she had fully recovered. Tetanus is usually diagnosed by clinical observation and does not rely on detection of antibodies, nor on identification of Clostridium tetani. In 2006, WHO tetanus vaccination guidelines recommended five to six vaccinations, and a booster every 10 years.1 An antibody titre presumed to be sufficient for immunisation can be reached after one dose in most elderly people.2 The absence of antibodies suggests that our patient was unable to produce an immune response to tetanus, in the presence of a haematological malignancy. Ageing,3 active lymphoma, chemotherapy,4 and rituximab5 can impair the immune response. No recommendations about tetanus prophylaxis procedures for wound management in patients with blood diseases are available, except for bone-marrow transplantation. For patients with dirty wounds who are elderly, have a haematological malignancy, or are on chemotherapy, a tetanus-specific single-step immunoassay should be done even if previous vaccination is apparently correct.1 If the assay results are negative, human tetanus immunoglobulins should be given. Large-scale immunisation programmes are the main reason for almost complete disappearance of tetanus in developed countries, but physicians should be aware of possible inadequate immunisation in particular groups.
References 1 Cooke M. Are current UK tetanus prophylaxis procedures for wound management optimal? Emerg Med J 2009; 26: 845–48. 2 Van Damme P, McIntyre P, Grimprel E, et al. Immunogenicity of the reduced-antigen-content dTpa vaccine (Boostrix[R]) in adults 55 years of age and over: a sub-analysis of four trials. Vaccine 2011; 29: 5932–39. 3 McQuillan G, Kruszon-Moran D, Deforest A, Chu SY, Wharton M. Serologic immunity to diphtheria and tetanus in the United States. Ann Intern Med 2002; 136: 660–66. 4 Van Tilburg C, Sanders E, Rovers M, Wolfs T, Bierings M. Loss of antibodies and response to (re-)vaccination in children after treatment for acute lymphocytic leukemia: a systematic review. Leukemia 2006; 20: 1717–22. 5 Pescovitz M, Torgerson T, Ochs H, et al. Effect of rituximab on human in vivo antibody immune responses. J Allergy Clin Immunol 2011; 128: 1295–302 e5.
www.thelancet.com Vol 380 August 4, 2012
An unexpected trismus Mikael Alves, Etienne Canoui, Lionel Deforges, Laurent Garderet, Bertrand Guidet, Georges Offenstadt, Eric Maury
In September, 2011, an 86-year-old woman was admitted to our medical intensive care unit with trismus and neck stiffness. 2 years earlier, she had been diagnosed with marginal zone lymphoma. Her medications included chlorambucil from January to October, 2010, followed by rituximab, cyclophosphamide, vincristine, and prednisone in March, 2011. Prednisone (20 mg per day) was maintained from March to August, 2011. 5 months before presentation, she had several falls and she received local care with 3 stitches for a chin wound in April 2011, and was given a first tetanus vaccination. She had not previously been vaccinated for tetanus and complete vaccination was proposed, but she refused. In August, 2011, she had another fall, resulting in a severe wound to her left leg. She was given oral amoxicillin clavulanate and daily wound care for a week. She reported 10 days afterwards, dysphagia, gait instability, dysarthria, stiffness of the neck, and intractable trismus. She was referred the same day to our hospital. On presentation, she was alert and fully oriented. Core temperature was 37°C. She was severely malnourished. Her weight was 42 kg, for a height of 152 cm, and she had diffuse muscle atrophy, skin fragility, and splenomegaly. The left calf wound was dry and clean. There was no limb weakness. Plantar responses were normal. Trismus with stiffness of the neck after a wound suggested tetanus. We aimed to rule out meningitis because of her underlying immunosuppression. CSF was normal and cultures remained negative. Tetanus antitoxin (500 IU) and tetanus vaccine (40 IU) were given. Mechanical ventilation and intravenous sedation were initiated.
Lancet 2012; 380: 536 Medical Intensive Care Unit (M Alves MD, E Canoui MD, Prof B Guidet MD, Prof G Offenstadt MD, Prof E Maury MD), Department of Haematology (L Garderet MD), and Inserm UMR S707 (Prof B Guidet, Prof G Offenstadt, Prof E Maury), Hospital Saint-Antoine, Paris, France; and Department of Bacteriology Hospital Henri Mondor, Creteil, France (L Deforges MD) Correspondence to: Dr Mikael Alves, Medical Intensive Care Unit, Hospital Saint-Antoine, 184 Rue du Fauborg Saint Antoine, Paris 75571, France [email protected]
Efficient protection, repeat antibody titre after 10 years
Tetanus antibodies titres
5 Efficient protection, repeat antibody titre within 5 to 10 years
Contributors MA, EC, LG, BG, GO, LD, and EM looked after the patient. MA, BG, GO, and EM wrote the report. Written consent to publication was obtained.
1 Efficient protection, repeat antibody titre after 2 years 0·5 Low protection, booster recommended 0·1
1 19 ,2
01 pe at Re
ta pe a Re
ab
bt
tit
itr e
re
:N
:D
ov
ec
25
,2
0, 2 Oc t3 e: ac cin hv
4t
01
1
01 1
11 20 5, Oc t e: ac cin dv
3r
ac cin 2n dv
1s
tv
ac
cin
e:
e: S
Ap
ep t2
r2
,2
,2
01 1
01 1
Detection threshold, no protection
Month, year
Figure: Vaccination record of our patient and international recommendations according to tetanus antibody titres
536
Because of continuing spasms, intrathecal baclofen (1200 μg per day) was started on day 3 with a good clinical response. It was stopped on day 8 because Pseudomonas aeruginosa meningitis was diagnosed; it resolved favourably with removal of the intrathecal catheter and intravenous ceftazidime. She experienced ventilator-associated pneumonia and was finally transferred to the rehabilitation ward on day 46. No antibodies to tetanus toxin were detected, by the tetanus ELISA IgG TestKit (Virotech, InGen, Chilly-Mazarin, France), on admission, or 30 days after each of three subsequent tetanus toxoid vaccinations. On day 58 after discharge from the intensive care unit, she had fully recovered. Tetanus is usually diagnosed by clinical observation and does not rely on detection of antibodies, nor on identification of Clostridium tetani. In 2006, WHO tetanus vaccination guidelines recommended five to six vaccinations, and a booster every 10 years.1 An antibody titre presumed to be sufficient for immunisation can be reached after one dose in most elderly people.2 The absence of antibodies suggests that our patient was unable to produce an immune response to tetanus, in the presence of a haematological malignancy. Ageing,3 active lymphoma, chemotherapy,4 and rituximab5 can impair the immune response. No recommendations about tetanus prophylaxis procedures for wound management in patients with blood diseases are available, except for bone-marrow transplantation. For patients with dirty wounds who are elderly, have a haematological malignancy, or are on chemotherapy, a tetanus-specific single-step immunoassay should be done even if previous vaccination is apparently correct.1 If the assay results are negative, human tetanus immunoglobulins should be given. Large-scale immunisation programmes are the main reason for almost complete disappearance of tetanus in developed countries, but physicians should be aware of possible inadequate immunisation in particular groups.
References 1 Cooke M. Are current UK tetanus prophylaxis procedures for wound management optimal? Emerg Med J 2009; 26: 845–48. 2 Van Damme P, McIntyre P, Grimprel E, et al. Immunogenicity of the reduced-antigen-content dTpa vaccine (Boostrix[R]) in adults 55 years of age and over: a sub-analysis of four trials. Vaccine 2011; 29: 5932–39. 3 McQuillan G, Kruszon-Moran D, Deforest A, Chu SY, Wharton M. Serologic immunity to diphtheria and tetanus in the United States. Ann Intern Med 2002; 136: 660–66. 4 Van Tilburg C, Sanders E, Rovers M, Wolfs T, Bierings M. Loss of antibodies and response to (re-)vaccination in children after treatment for acute lymphocytic leukemia: a systematic review. Leukemia 2006; 20: 1717–22. 5 Pescovitz M, Torgerson T, Ochs H, et al. Effect of rituximab on human in vivo antibody immune responses. J Allergy Clin Immunol 2011; 128: 1295–302 e5.
www.thelancet.com Vol 380 August 4, 2012