A Case of Mistaken Identity: Natalizumab, Dermatographia and Infusion Reaction

Introduction:To describe the appearance of dermatographia (dermatographic urticaria) that occurred during the course of Natalizumab infusions and was mistaken for an infusion reaction.

Background:  Natalizumab is an available and effective disease modifying therapy (DMT) to treat relapsing forms of Multiple Sclerosis (MS).   Natalizumab discontinuations can occur due to infusion reactions.

Case Report:  58 year old female with RRMS developed a rash starting at the site of the IV access for natalizumab  during  2^nd infusion.  Diagnosed as infusion reaction, described as erythematous macular pruritic rash at the site of the infusion both proximally and distal to the IV access (Figure A). Infusion rate was slowed at the onset of the rash and after persistence and increased rash size, immediately discontinued. Treated  with antacid, antihistamine and IV steroids with prompt resolution. Next infusion had same symptoms.  Serological testing was negative for Natalizumab blocking antibodies. Patient premedicated for 4^th infusion but developed same symptoms.  No systemic signs or symptoms of allergy or anaphylaxis were noted at any time. Office visit was remarkable for the absence of allergies of significance but examination identified a reproducible inducible rash - skin wheal and flare, (induced by scratching and skin rubbing) that provoked the same appearance of  localized superficial rash that occurred at the time of Natalizumab infusion. (Figure B).  This skin reaction occurred with all further infusions but patient had no other symptoms and remained on Natalizumab.

Discussion: Dermatographia or dermatographic urticaria (known as skin writing) is a skin disorder seen in ~5% of the population, generally teenagers and young adults. It is a common type of urticaria where the skin becomes raised and inflamed when stroked, scratched or rubbed.  The symptoms are thought to be caused by mast cells in the surface of the skin releasing histamines without the presence of antigens. The underlying cause of this disorder is unknown and it can last for years.  Dermatographia can be treated by agents that prevent the release of histamine and or in combination with H1 antagonists or H2 receptor antagonists.  The presence of this skin lesion does not reflect a reaction to treatment

Conclusion: Not all skin reactions that occur during or after Natalizumab infusion reflect allergic or serious reactions necessitating therapy discontinuation. Vigilance and accurate identification of skin reactions occurring during infusion or thought to be related to natalizumab treatment is needed to determine the appropriate course of treatment. Differentiating serious skin reactions from non-serious  or unrelated reactions are important for clinicians and infusion staff to be aware of so that appropriate treatment , adjustment or modification of treatment plan and infusion care needs are addressed.