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      Combined Reduced-Antigen Content Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Vaccine-Related Erythema Nodosum: Case Report and Review of Vaccine-Associated Erythema Nodosum

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          Abstract

          Background

          Vaccination programs reduce the morbidity and mortality of diphtheria, pertussis, and tetanus. Erythema nodosum is a reactive erythema that can be associated with infections, drugs, and many conditions. The new onset of erythema nodosum after receiving vaccination is uncommon.

          Purpose

          Combined reduced-antigen content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine-associated erythema nodosum is described and the reports of vaccine-related erythema nodosum are summarized.

          Methods

          The clinical features of a 39-year-old woman who developed erythema nodosum after receiving Tdap vaccine are reported. Using the PubMed database, an extensive literature search was performed on erythema nodosum, vaccine, and vaccination.

          Results

          Tdap, the most commonly used booster vaccine against tetanus, diphtheria, and pertussis, is well tolerated in all age groups. Local injection-site reactions are the most common adverse events, whereas headache, fatigue, gastrointestinal symptoms, and fever are the most frequent systemic events. Erythema nodosum has not previously been reported in patients who have received Tdap vaccine. The patient developed erythema nodosum within 48 h after receiving Tdap vaccine; her symptoms cleared and nearly all skin lesions resolved within 2 weeks after initiating oral treatment with ibuprofen, fexofenadine, and prednisone. Vaccine-associated erythema nodosum has previously been reported following vaccination for cholera, hepatitis B, human papillomavirus, malaria, rabies, small pox, tuberculosis, and typhoid.

          Conclusion

          Vaccine-associated erythema nodosum is uncommon. Erythema nodosum occurring after Tdap vaccination is a rare, yet potential, adverse effect.

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          Most cited references23

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          Phase 1 Trial of Malaria Transmission Blocking Vaccine Candidates Pfs25 and Pvs25 Formulated with Montanide ISA 51

          Background Pfs25 and Pvs25, surface proteins of mosquito stage of the malaria parasites P. falciparum and P. vivax, respectively, are leading candidates for vaccines preventing malaria transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed the safety and immunogenicity of recombinant Pfs25 and Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion. Methodology/Principal Findings The trial was conducted at The Johns Hopkins Center for Immunization Research, Washington DC, USA, between May 16, 2005–April 30, 2007. The trial was designed to enroll 72 healthy male and non-pregnant female volunteers into 1 group to receive adjuvant control and 6 groups to receive escalating doses of the vaccines. Due to unexpected reactogenicity, the vaccination was halted and only 36 volunteers were enrolled into 4 groups: 3 groups of 10 volunteers each were immunized with 5 µg of Pfs25/ISA 51, 5 µg of Pvs25/ISA 51, or 20 µg of Pvs25/ISA 51, respectively. A fourth group of 6 volunteers received adjuvant control (PBS/ISA 51). Frequent local reactogenicity was observed. Systemic adverse events included two cases of erythema nodosum considered to be probably related to the combination of the antigen and the adjuvant. Significant antibody responses were detected in volunteers who completed the lowest scheduled doses of Pfs25/ISA 51. Serum anti-Pfs25 levels correlated with transmission blocking activity. Conclusion/Significance It is feasible to induce transmission blocking immunity in humans using the Pfs25/ISA 51 vaccine, but these vaccines are unexpectedly reactogenic for further development. This is the first report that the formulation is associated with systemic adverse events including erythema nodosum. Trial Registration ClinicalTrials.gov NCT00295581
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            Erythema nodosum: a sign of systemic disease.

            Erythema nodosum, a painful disorder of the subcutaneous fat, is the most common type of panniculitis. Generally, it is idiopathic, although the most common identifiable cause is streptococcal pharyngitis. Erythema nodosum may be the first sign of a systemic disease such as tuberculosis, bacterial or deep fungal infection, sarcoidosis, inflammatory bowel disease, or cancer. Certain drugs, including oral contraceptives and some antibiotics, also may be etiologic. The hallmark of erythema nodosum is tender, erythematous, subcutaneous nodules that typically are located symmetrically on the anterior surface of the lower extremities. Erythema nodosum does not ulcerate and usually resolves without atrophy or scarring. Most direct and indirect evidence supports the involvement of a type IV delayed hypersensitivity response to numerous antigens. A deep incisional or excisional biopsy specimen should be obtained for adequate visualization. Erythema nodosum represents an inflammatory process involving the septa between subcutaneous fat lobules, with an absence of vasculitis and the presence of radial granulomas. Diagnostic evaluation after comprehensive history and physical examination includes complete blood count with differential; erythrocyte sedimentation rate, C-reactive protein level, or both; testing for streptococcal infection (i.e., throat culture, rapid antigen test, antistreptoly-sin-O titer, and polymerase chain reaction assay); and biopsy. Patients should be stratified by risk for tuberculosis. Further evaluation (e.g., purified protein derivative test, chest radiography, stool cultures) varies based on the individual. Erythema nodosum tends to be self-limited. Any underlying disorders should be treated and supportive care provided. Pain can be managed with nonsteroidal anti-inflammatory drugs.
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              Erythema nodosum and erythema induratum (nodular vasculitis): diagnosis and management.

              Erythema nodosum is the most common type of panniculitis; it may be due to a variety of underlying infectious or otherwise antigenic stimuli. The pathogenesis remains to be elucidated, but both neutrophilic inflammation and granulomatous inflammation are implicated. Beyond treating underlying triggers, therapeutic options consist mainly of nonsteroidal anti-inflammatory drugs, symptomatic care, potassium iodide, and colchicine. Erythema induratum (nodular vasculitis) is a related but distinctly different clinicopathologic reaction pattern of the subcutaneous fat. It is classically caused by an antigenic stimulus from Mycobacterium tuberculosis but may be associated with several other underlying disorders. After appropriate antimicrobial treatment in tuberculous cases, therapy for erythema induratum is similar to options for erythema nodosum.
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                Author and article information

                Contributors
                mitehead@gmail.com
                Journal
                Dermatol Ther (Heidelb)
                Dermatol Ther (Heidelb)
                Dermatology and Therapy
                Springer Healthcare (Heidelberg )
                2193-8210
                2190-9172
                1 November 2013
                1 November 2013
                December 2013
                : 3
                : 2
                : 191-197
                Affiliations
                Division of Dermatology, University of California San Diego, San Diego, CA 92131-3643 USA
                Article
                35
                10.1007/s13555-013-0035-9
                3889310
                24318418
                ced4ff84-a18e-45a6-baba-27244915e86f
                © The Author(s) 2013
                History
                : 23 September 2013
                Categories
                Case Report
                Custom metadata
                © Springer Healthcare 2013

                Dermatology
                acellular pertussis,dermatology,diphtheria,erythema nodosum,tdap,tetanus,vaccine,vaccine-associated,vaccine-related,vaccination

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