Q:

5/31/2015  
What would be the treatment for cellulitis like reaction at the injection area and surrounding arm? Pain management? What if the swelling progressed more than few days?

A:


I am assuming that since you use the term “cellulitis like reaction” we are not considering infectious complications of an injection but either acute or delayed local reactions. These local responses can be acute/immediate or delayed or both. The mechanisms are also variable and often vary with the substance in the injection. Certainly for allergy injections this local reaction can be due to specific-IgE related to the allergen content of the allergy vaccine. Immunization reactions can be due to a local IgE-dependent allergy but more likely may be due to specific-IgG to the immunogen or an irritant response. All of these reactions are self- limited and are generally treated with cold or warm compresses, symptomatic treatment with antihistamines if itching, and corticosteroid topically to reduce warmth, erythema and tenderness, particularly if the reaction progressed over several days. I do not generally suggest oral corticosteroids, although this may be of some benefit. I sometimes suggest oral nonsteroidal anti-inflammatory therapy as well. Proof of efficacy, other than measures that relieve symptoms, is sparse.

I have enclosed an archived question from Ask The Expert that provide more detail and references related to local reactions to vaccination.

Local reaction to Pneumovax and administration of Prevnar
Q: 4/20/2015
If a patient had a significant, but local, injection site reaction to Pneumovax23, is it safe/appropriate to administer an indicated Prevnar 13?

A: I am not clear what is meant by “significant, but local” reaction. In general, a local reaction would not preclude subsequent administration of a vaccine, even if the same vaccine. Local reactions are seldom of clinical significance, though they are uncomfortable and source of some angst. In general local reactions reflect either an irritation or prevaccine immunity to a component of the vaccine. If the reaction were immediate and associated with itching followed by delayed inflammation, this may reflect a late phase IgE mediated response. Even that would not contraindicate subsequent administration. Because of multiple serotypes in the pneumococcal vaccines, it is not unusual to have a local response following administration (see Ask The Expert question below, up to 50% of Pneumovax recipients experience a large local reaction).

I have copied quotes from the practice parameter on adverse reactions to vaccines published in 2012. This is a great reference. Adverse Reactions to Vaccines Practice Parameter 2012

“Summary Statement 1: Mild local reactions and constitutional symptoms, such as fever, after vaccinations are common and do not contraindicate future doses. Rarely, delayed-type hypersensitivity to a vaccine constituent can cause an injection-site nodule, but this is not a contraindication to subsequent vaccination. (C)

Local injection-site reactions (swelling, redness, and/or soreness) and constitutional symptoms, especially fever, are common after the administration of most vaccines and are not contraindications to subsequent vaccination.11 Neomycin is contained in several vaccines.12 For those reporting a delayed-type hypersensitivity contact dermatitis to neomycin, the only anticipated reaction is a small temporary papule at the injection site,13,14and this is not a contraindication to subsequent vaccination.11 Delayed type hypersensitivity to thimerosal has also been reported.15 Although patients with a positive patch test result for thimerosal can have large local reactions to vaccination with thimerosal containing vaccines,16,17 most such patients do not.15,18-20 Neither a history of such reactions nor a positive patch test result to thimerosal is a contraindication to future vaccination.11 There is a single case report of a generalized pruritic maculopapular rash attributed to thimerosal in an influenza vaccine.21 Aluminum-containing vaccines12 rarely cause persistent nodules at the injection site, possibly because of delayed hypersensitivity or other immune responses to aluminum.22-24 About 5% of immunizations with tetanus toxoid–containing vaccines cause large local swelling at the injection site.104,105 This probably represents an Arthus reaction in patients with preexisting IgG anti-tetanus antibodies from prior immunizations who then receive a large injection of antigen in the vaccine. These reactions can cause discomfort but are not serious.

I have attached an archived Ask The Expert question that is also relevant.

In summary, it is not recommended that Prevnar be given for 6-12 months after Pneumovax as the response to Prevnar may not be ideal. Therefore, if the time frame is appropriate and Prevnar is indicated, I would administer. I would advise the patient that a local reaction is expected and treat with nonsteroidal anti-inflammatory drug or acetaminophen if not contraindicated and use oral or topical antihistamine if itching is noted.

Large local reaction after pneumococcal vaccine
Q: 2/2/2012
I had an 11 year old girl who had recurrent infections that did not have greater than 50% positive pneumococcal titers, so I told her mother to get pneumovax in order to recheck her titers. She did have good titers to 6/14 that we checked - after the shot she developed significant arm swelling, nausea, and went to the ER. Per the mother, the blood work consistent with an infection/dx as cellulitis. This sounds most plausible to me, but is it possible that because she had a few positive titers that giving her the vaccine elicited some large immune reaction?

A: Unfortunately, I am not going to be able to give you a definitive answer to your inquiry, but I can point you to literature which allows us to construct a reasonably good hypothesis as to the nature of the reaction that your patient experienced.

First of all, as you can see from the literature copied below which is taken from several sources, local reactions to pneumococcal immunization are not uncommon. Of course, large locals are much rarer than those of modest proportion, but they do occur with significant frequency. Also, as you can see, some are also associated with systemic symptoms and some have been labeled as cellulitis. So, the description you present could well have been due to a local reaction to pneumococcal vaccine.

In addition, with the systemic symptoms that she experienced, I am not sure that blood work would be able to distinguish between an infectious cellulitis and a local reaction with systemic symptoms. One might expect, in both, that the white count might be elevated and that there might be a shift to the left. We have seen patients with large locals and systemic reactions exhibit elevations in neutrophils with left shifts.

Unfortunately, no one can answer the question as to whether or not the preexisting titers to pneumococcus antigens would have predisposed your patient to such reaction, but we do know, as you can see from the information copied below, that large locals and systemic reactions occur more frequently and are more severe in general after revaccination. This of course implies that the response is anamnestic, and therefore may well be due to preexisting antibodies.

In summary, I think based upon this information, it is not unlikely that your patient did experience a large local with systemic symptoms to immunization. The mechanism underlying this reaction cannot be determined with confidence, but based on the fact that such reactions occur more frequently in previously immunized individuals, antibodies to pneumococcus could possibly be playing a role.

"Local reactions at injection site including soreness, warmth, erythema, swelling and induration. In post-marketing experience, injection site cellulitis-like reactions were reported rarely; between 1989 and 2002, when approximately 43 million doses were distributed, the annual reporting rate was 2/100,000 doses. These cellulitis-like reactions occurred with initial and repeat vaccination at a median onset time of 2 days after vaccine administration and were transient in nature. Compared with primary vaccination, an increased rate of self limited local reactions has been observed with revaccination at 3-5 years following primary vaccination.

Fever: Other adverse experiences reported in clinical trials and/or in post-marketing experience include: Body as a Whole Cellulitis”
SOURCE: Package insert, Pneumovax23
Adverse reactions to Pneumovax 23
Pneumovax 23 vaccine is known to be associated with a high rate of local injection site reactions. The majority of these are mild, with redness, swelling, pain and a feeling of heat around the site where the injection was given and recovery within a couple of days. Some reactions can result in extensive swelling and pain that can limit the use of the arm. Cellulitis-like reactions and abscesses can also occur.

Injection site reactions are very common but very severe reactions such as cellulitis-like reactions and abscesses are rare. More information about possible adverse reactions is available in the Pneumovax 23 Product Information (PI), which has recently been revised. SOURCE: Australian Government Department of Health and Aging

In a clinical trial, an increased rate of local reactions has been observed with revaccination at 3 to 5 years following primary vaccination. This increase was greater among subjects ¡Ý65 years of age (79.3% vs 52.9%) than among subjects 50 to 64 years of age (79.6% vs 72.8%). In both age groups, revaccinees reported a higher rate of a composite end point (any of the following: moderate pain, severe pain, and/or large induration at the injection site) than primary vaccines (age ¡Ý65 years: 30.6% vs 10.4%; age 50 to 64 years: 35.5% vs 18.9%). The rate of vaccine-related systemic adverse experiences was higher following revaccination than primary vaccination in subjects ¡Ý65 years of age (33.1% vs 21.7%), and was similar following revaccination and primary vaccination in subjects 50 to 64 years of age (37.5% vs 35.5%). SOURCE: MERCK VACCINES

Allergy Asthma Proc. 2008 Jul-Aug;29(4):397-9.
Systemic reaction to pneumococcal vaccine: how common in pediatrics?
Yousef E, Mannan S.
Source
Division of Allergy and Immunology, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19899, USA.
Abstract
The 23-valent-polysaccharide pneumococcal vaccine (PPV23) is currently recommended for patients at high risk for invasive disease from Streptococcus pneumoniae. It is also frequently used in the evaluation of patients with suspected immunodeficiency. Reports of systemic adverse reactions are rare. Our objective is to describe a patient with an apparent systemic reaction to PPV23 and review our hospital's 2-year experience with pneumococcal vaccine. Chart review of 173 patients given PPV23 between January 1, 2004 and December 31, 2005 revealed five who had significant adverse reactions, including local cellulitis, fever, and vomiting. Variables considered included age at immunization, indication for PPV23, and prior pneumococcal vaccines. The mean age of all patients given PPV23 during the defined time period was 8.6 years, and the most common indication for vaccination was recurrent infection. Of those patients who had adverse reactions, the mean age was 6.5 years. The time from prior pneumococcal vaccination was a mean of 20 months in children who did not have an adverse reaction. None of the patients who had an adverse reaction had documentation of receiving PPV23 before. Local reactions to PPV23 occur in approximately 50% of recipients, and revaccination of immunocompetent individuals increases the risk for local reaction. Systemic reactions are less common and only occur in approximately 1% of recipients. Our patient had no identifiable risk factors for development of an adverse reaction. Additional studies are indicated to determine whether there are identifiable risk factors for the development of adverse reactions to PPV23.

Sincerely,
Phil Lieberman, M.D.

I hope this information is of help to you and your patient.

All my best.
Dennis K. Ledford, MD, FAAAAI

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