What are the common side effects of intradermal injections in dermatology and how can they be prevented?

Side Effects of Intradermal Injections in Dermatology

The most common side effects of intradermal injections in dermatology are local injection site reactions including redness, swelling, pain, itching, and induration, occurring in the majority of patients, with proper technique and patient education preventing most complications. 1

Common Local Reactions

Immediate Reactions (Within Days)

• Redness, swelling, pain, itching, and bruising occur at the injection site in most patients receiving intradermal injections, with these reactions being generally mild to moderate and self-limiting 1, 2
• Discoloration and edema are transient effects that typically resolve spontaneously without intervention 3, 4
• Visible wheal or papule formation (6-10 mm diameter) is expected with proper intradermal technique and confirms correct placement 5
• Bleeding at the injection site may occur but is typically minimal 6

Delayed Reactions (Weeks to Months)

• Palpable papules and nodules can develop several weeks after injection, are generally asymptomatic and nonvisible, and typically resolve spontaneously 3
• Maldistribution of product may occur due to suboptimal injection technique, leading to visible irregularities 7, 4

Serious but Rare Complications

Severe Cutaneous Reactions

• Skin necrosis can occur from intradermal injections, particularly with certain products like lyophilized exosomes, presenting as dark red bumps that transform into painful, non-blanchable purplish papules and nodules with central crusted erosions 8
• Foreign body granulomas are very rare (incidence 0.01%-0.1%) but represent a serious late complication that may appear months or years post-injection and can persist or grow over time 3, 4
• Leukocytoclastic vasculitis and eccrine necrosis have been documented in severe cases of adverse reactions to intradermal injections 8

Infectious Complications

• Infection at the injection site, including atypical mycobacteria or biofilm formation, can occur as both early and late complications 7, 4

Hypersensitivity Reactions

• Delayed type IV hypersensitivity reactions are the most common immunologic complication, though rare type I immediate reactions can also occur 7
• Late-onset allergic reactions may develop weeks to months after injection 4

Prevention Strategies

Proper Injection Technique

• Use 30-gauge, 4mm length needles inserted at shallow angles with bevel facing upward to ensure proper intradermal placement and avoid deeper structures 5
• Create visible papules or wheals with blanching during injection to confirm proper intradermal placement and avoid placing product into deeper vasculature 5
• Aspirate the needle prior to each injection to detect intravascular placement and prevent introducing material directly into vessels 5
• Use incremental injections rather than large boluses to minimize vascular compression and allow early detection of complications 5

Product Preparation and Handling

• Ensure optimal product reconstitution when using materials that require preparation, as suboptimal reconstitution is a major cause of papules and nodules 3
• Avoid unapproved products or administration methods, particularly with newer agents like exosomes, as these carry unpredictable risks of adverse reactions 8

Patient Education and Training

• Educate patients about expected local reactions (redness, swelling, pain) that occur within days and typically resolve within 2 weeks 4
• Train patients on proper injection technique when self-administering biologics, as almost all local reactions to subcutaneously administered biological agents can be prevented by changing injection techniques 2
• Inform patients that most reactions occur during the first month of treatment and subsequently decrease in frequency 6

Site Selection and Monitoring

• Maintain awareness of vascular anatomy to avoid major vessels, particularly when injecting in high-risk areas 5
• Avoid deep injections that could reach the hypodermis where major vessels reside 5

Management of Complications

Mild to Moderate Reactions

• Provide reassurance that reactions typically diminish with ongoing therapy without requiring treatment discontinuation 6
• Consider symptomatic treatment with topical measures for persistent or bothersome reactions 6

Severe Reactions

• Administer oral corticosteroids (e.g., prednisolone for 7 days) for severe reactions such as skin necrosis with vasculitis 8
• Use intralesional steroid injections for persistent nodules, granulomas, or late-onset allergic reactions, often requiring repeated doses to establish the right amount 4
• Combine 5-fluorouracil with steroid injections for technical complications such as superficial implantation of long-lasting fillers 4
• Consider vascular lasers, intense pulsed light, dermabrasion, or shaving for adverse events lasting longer than 2 weeks attributable to technical shortcomings 4

When to Discontinue Treatment

• Continue therapy unless a severe allergic reaction occurs, as most injection site reactions do not correlate with drug efficacy or development of antidrug antibodies 6, 2
• Reserve surgical excision as the last option, indicated only for hard lumps in the lips and visible hard nodules or granulomas in the subcutaneous fat 4

Critical Pitfalls to Avoid

• Do not misunderstand the pathophysiology of injection site reactions as most are not allergic or immunogenic, and misunderstanding may result in unnecessary treatment discontinuation 2
• Do not inject too superficially with long-lasting fillers, as this technical error leads to prolonged adverse events requiring intervention 4
• Do not use unapproved administration routes for products only approved for topical use, as this dramatically increases complication risk 8