Elsevier

Vaccine

Volume 29, Issue 40, 16 September 2011, Pages 6830-6833
Vaccine

Short communication
Atraumatic osteonecrosis of the humeral head after influenza A-(H1N1) v-2009 vaccination

https://doi.org/10.1016/j.vaccine.2011.07.052Get rights and content

Abstract

In the recent pandemic influenza A-(H1N1) v-2009 vaccination campaign, adjuvanted vaccines have been used because of their antigen-sparing effect. According to available reports, the rate of severe vaccination reactions has not increased, as compared with previous seasonal influenza vaccinations.

Here we describe an adult female patient who was vaccinated with an AS03 adjuvanted split-virus vaccine injected into the left arm. She experienced a prolonged and painful local reaction for 4 weeks. During this time, persistent incapacitating pain shifted into the left shoulder. Magnetic resonance imaging (MRI) at the injection site detected atraumatic humeral head osteonecrosis in conjunction with bursitis of the rotator cuff region. Clinical and laboratory examination revealed no other underlying disease. Using analgetic medication and physical therapy, resting pain completely remitted within the following 14 weeks. Pain on exertion declined within the following 6 months.

Atraumatic osteonecrosis, a relatively rare disorder which initially presents non-specific clinical symptoms, has never been associated with parenteral influenza vaccination. Although the available data cannot establish a causal relationship, our patient's clinical course – with a continuous transition from increased local post-vaccination reactions to symptoms of a severe shoulder lesion with osteonecrosis – raises the question of a pathogenetic link. Considering the vascular pathogenesis of osteonecrosis, we hypothesize that our patient's enhanced local immunologic reaction may have led to regional vasculitis as the cause of bone destruction. As mild forms of osteonecrosis may have escaped previous clinical attention, it is the purpose of our report to increase awareness of this exceptional event as a possible side effect of parenteral adjuvanted vaccination.

Introduction

In spring 2009, the emergence of the new influenza type A-(H1N1) virus initiated a pandemic with a rapid global extension within a few months. Initial observations of increased mortality rates and of unusually high rates of severe complications of infected persons in Mexico and the United States led to a worldwide vaccination campaign as recommended by the World Health Organization and governmental authorities of several countries [1]. New vaccine formulations needed to be manufactured within a relatively short time. Some of them contained adjuvants to enhance the immune response in conjunction with an antigen-sparing effect in the presence of limited manufacturing capacities [2], [3], [4].

Mainly in Germany, the adjuvanted split-virus vaccine Pandemrix™ (GlaxoSmithKline) containing a relatively novel oil-in-water emulsion (AS03) was used for influenza A-(H1N1) v-2009 vaccination. Confirming previous tests with the new adjuvant [5], [6], [7], surveillance reports described more intense local reactions and increased rates of mild general symptoms, as compared with seasonal influenza vaccines [8], [9], [10], [11], [12]. But those surveillance reports found no increase in the frequency of rare, severe adverse effects such as anaphylactic reactions, neurologic complications, or vasculitis.

Here we report the occurrence of a single case of atraumatic osteonecrosis of the humeral head after an influenza A-(H1N1) v-2009 vaccination with the AS03 adjuvanted vaccine. To the best of our knowledge, osteonecrosis has never been associated with any form of vaccination. Although the available data cannot establish a causal relationship, our patients clinical course suggests a pathogenetic link between vaccination and osteonecrosis. The purpose of our report is to increase awareness of this severe event as a possible, exceptional side effect of parenteral influenza vaccination.

Section snippets

The clinical case

In November 2009, a 48-year-old female physician without previous disease underwent an influenza A-(H1N1) v-2009 vaccination with Pandemrix™ (A81CA061A, GlaxoSmithKline) by a single injection into the anterolateral portion of the deltoid muscle of the left arm. About 2½ h after vaccination a pronounced and painful local swelling with redness and hardening of the skin and deeper tissue layers developed at the injection site. Within the next 4 weeks, the swelling and redness slowly declined but

Discussion

Osteonecrosis is a well-known complication of severe, proximal bone injuries; according to current pathogenetic concepts it is due to an interruption of the local blood supply of the affected bone [13]. Its atraumatic form is associated with a variety of conditions, including long-term corticoid administration, alcohol abuse, hemoglobinopathies, dysbarism, and immune disorders such as connective tissue disease and vasculitis [14], [15]. The precise pathogenesis remains obscure, and a

Conclusion

Considering the millions of persons [10] who have been vaccinated with adjuvanted vaccines, humeral osteonecrosis – if induced by vaccination in our patient – has to be considered an exceptional event. Therefore, its occurrence does not alter the relation between benefits and risks of the recent pandemic vaccination campaign. Yet because of its clinical course which is characterized by the insidious and delayed onset of nonspecific shoulder symptoms, it is possible that mild forms previously

Acknowledgement

We thank Mary Knatterud, Ph.D., Associate Professor, Department of Surgery, College of Medicine, University of Arizona, for helpful comments and editorial assistance.

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