Cutaneous vaccination reactions

Cutaneous vaccination reactions are potential symptoms of the skin after a vaccination. Different phenotypes emerge, which are probably associated with different immune reactions with different effector cells. Current knowledge of the triggering mechanisms and their immunological pathomechanisms is still fragmentary. The organ lends itself to further exploration. The skin is an immunosensitive organ, frequently involved in vaccination reactions, already well studied and easily accessible to clinical observation and laboratory testing. It is virtually the organ in which expected (desired) and unexpected (undesired/pathogenic) local or systemic vaccination reactions are focused like a burning glass. The expected vaccination reactions as an expression of the immune system's desired reaction to the vaccine usually subside completely after a few days.

Information on the type and frequency of ADRs can be found in the product information of the respective vaccine.

Cutaneous adverse vaccination reactions can be classified into three pathogenetic phenotypes:

1. excessive (hyperergic) reactions of the immune system activated by the vaccination

• Local reactions at the injection site (e.g. itchy or painful swelling within 24 hours of injection or delayed, occurring around 7 days after injection (keyword: COVID arm)
• Systemic reactions (10-30% of all cutaneous vaccination reactions related to COVID-19 vaccinations; w:m=9:1 (McMahon et al.2021)
  • Frequent:
    • morbilliform, papulo-vesicular papulo-squamous exanthema
    • Urticaria (hyperergic urticaria; about 10% of COVID-19 vaccine exanthema; urticaria usually occurs >24h after vaccination; persists only about 3-5 days; it does not recur regularly when boosted.
    • Angioedema (hyperergic angioedema/about 5% of COVID-19 vaccination reactions)
  • Rare (few or only individual case descriptions):
    • Acute febrile neutrophilic dermatosis (COVID-19, influenza)
    • Erythema exsudativum multiforme (COVID-19, HPV, measles-mumps-rubella, varicella, hepatitis B, meningococcal pneumonia)
    • Stevens-Johnson syndrome
    • Toxic epidermal necrolysis (TEN )
    • Acute generalized exanthematous pustulosis (AGEP)
    • DRESS
    • Pityriasis lichenoides chronica (COVID-19/measles-mumps-rubella vaccines)
    • Erythromelalgia (face and extremities after influenza and hepatitis B vaccination -Rabaud C et al. 1999)
    • Perniones (COVID-19/Freeman EE et al. 2020)
    • Gianotti-Crosti syndrome (hepatitis B virus vaccination/Karakaş M et al. 2007).

2. allergic reactions to vaccine/adjuvants (e.g. alpha-gal, dextrans, chicken protein, PEG)

• Local reactions (itchy, inflammatory nodules/nodules or plaques at the vaccination site; usually only weeks/months after injection; possible late reaction to aluminum hydroxide or other adjuvants; later granulomatous reactions to hyaluronic fillers are unexplained (Munavalli GG et al. 2022).
• Systemic reactions
  • Anaphylactic reactions (1-2h after injection; the incidence is 1-10 cases per¹⁰⁶ vaccinated persons)
  • Serum sickness with exanthema and fever
  • Leukocytoclastic vasculitis (predominantly IgA vasculitis, a few days to weeks after vaccination-influenza, COVID-19, pneumococci)
  • Erythema exsudativum multiforme

3. immunological dysregulations (with misdirected immunosuppressive/immundivergent reactions)

This refers to inflammatory processes that are not primarily directed against the vaccine antigen. If there is a corresponding susceptibility, this leads to the initial manifestation, reactivation or intensification of genuin diseases.

• Reactivated herpes simplex infections (influenza/hepatitis vaccinations, after COVId-19 HSV recurrences = 3rd most frequent ADR)
• Erythema multiforme in the wake of reactivated herpes simplex
• Pityriasis rosea (classic form)
• Guttate type of psoriasis vulgaris (in 3% of psoriatic patients, both as a flare-up reaction or as a worsening of the existing psoriasis type. The time intervals vary: a few days to months after vaccination. Psoriatic flare-ups have been described after COVID-19, influenza, diphtheria-tetanus-pneumococcal vaccinations)
• Lichen (ruber) planus (a few days to months after hepaitis B and COVID vaccinations/Calista D et al. 20004, Zengarini C et al. 2022)
• Exacerbation of atopic dermatitis
• Flare-up reaction in dermatomyositis (COVID-19 vaccination/Kussini J et al. 2025)
• Autoimmunological blistering (COVID-19, measles-mumps-rubella, diphtheria-pertussis-tetanus vaccinations)
• Recall reactions (flare-up reactions, e.g. at sites previously treated with imiquimod)

Different immune reactions with different effector cells are associated with the cutaneous phenotypes of (pathogenic) cutaneous vaccination reactions. Knowledge of the triggering mechanisms and the consecutive immunopathogenetic processes is still fragmentary. The skin as an immunosensitive organ has already been well studied and is easily accessible to clinical observations and laboratory tests. It is virtually a mirror of expected (physiological) and pathogenic local or systemic vaccination reactions.

w>m

Surveys on the incidence of cutaneous vaccination reactions showed that >70% of those vaccinated developed localized and about 3-5% generalized skin reactions.

Autoimmune reactions following vaccination: The mechanism of autoimmune reactions following vaccination is still unclear. On the one hand, a genetic predisposition to vaccine-induced autoimmunity is suspected, as only a few test subjects developed autoimmune diseases after vaccination. On the other hand, the immune system could trigger autoimmune diseases through cross-reactivity due to the similarity of some vaccine components with certain human proteins (so-called molecular mimicry). In addition, it has been postulated that activation of the toll-like receptors of antigen-presenting cells may play a role in the recurrence of autoimmune diseases after vaccination (Sagy I et al. 2022). It is known that tetanus toxoid, influenza and polio vaccines as well as other vaccines have an influence on the formation of autoantibodies and the development of autoimmune diseases such as rheumatoid arthritis, bullous pemphigoid, pemphigus vulgaris, autoimmune myositis and systemic lupus erythematosus (Hinterseher J et al. 2023). Furthermore, influenza vaccines have been reported to trigger a transient flare in approximately 19.4% of patients with SLE within 6 weeks (Crowe SR et al. 2011). There are also some cases in which SLE occurred after vaccination against hepatitis B, tetanus or typhoid fever.

See also Autoimmune diseases of the skin and SARS-CoV-2 vaccination

1. Calista D et al. (2004) Lichen planus induced by hepatitis B vaccination: a new case and review of the literature. Int J Dermatol 43:562-564.

2. Crowe SR et al. (2011) Influenza vaccination responses in human systemic lupus erythematosus: impact of clinical and demographic features. Semin Arthritis Rheum. 63: 2396-2406.

3. Freeman EE et al. (2020) Pernio-like skin lesions associated with COVID-19: A case series of 318 patients from 8 countries. J Am Acad Dermatol 83:486-492.

4. Hinterseher J et al. (2023) Autoimmune skin diseases and SARS-CoV-2 vaccination - a meta-analysis.JDDG 21: 853-862

5. Karakaş M et al. (2007) Gianotti-Crosti syndrome in a child following hepatitis B virus vaccination. J Dermatol 34:117-20
6. Kussini J et al (2025) Cutaneous reactions to vaccination. J Dtsch Dermatol Ges 23:195-209.
7. McMahon DE et al. (2021) Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases. J Am Acad Dermatol 85: 46-55.

8. Munavalli GG et al. (2022) COVID-19/SARS-CoV-2 virus spike protein-related delayed inflammatory reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and treatment. Arch Dermatol Res 314:1-15.

9. RKI (2021) Communications of the Robert Koch Institute (RKI) in Berlin. Retrieved on 26.1.2021
10. Sagy I et al. (2022) New-onset systemic lupus erythematosus following BNT162b2 mRNA COVID-19 vaccine: a case series and literature review. Rheumatol Int 42: 2261-2266.

11. Zengarini C et al. (2022) Lichen Ruber Planus occurring after SARS-CoV-2 vaccination. Dermatol Ther. 35:e15389.

12. van Buchem-Post NF et al. (2025) Impact of COVID-19 disease and vaccination on dermatological immune-mediated inflammatory diseases atopic dermatitis, psoriasis, and vitiligo: a Target2B! substudy. J Dermatol 52:624-633.