Chronic Inducible Urticaria (CIndU)/Physical Urticaria

Protection from and avoidance of the physical cause of the reaction is ideal, but often  impractical. 

• Consider protective clothing or modifying daily activities.

• Delayed pressure: pressure is a function of weight and contact surface; if weight cannot be decreased, area of contact should be maximized 

• Solar: protective clothing, sunscreen

• Cold: water temp > 25°C (77°F) safe for most patients [18] 

Treatment can help reduce symptoms, as well as increase trigger thresholds

Epinephrine if systemic symptoms, cold urticaria (especially if frequent and unavoidable cold exposure, high temperature threshold) 

Topical medications: 

• Emollients can be tried if xerosis present in patients with dermographism

• Barrier cream may be tried in aquagenic urticaria [19], topical capsaicin for heat/cold urticaria (may cause irritation) [20] 

First and second-line systemic medications: 

• Typical CSU treatments, including second generation H1 anti-histamines

  • Start at standard doses, may increase up to 4 times standard dosing per  CSU guidelines [1, 9]

  • 1st generation H1 anti-histamine or doxepin may be used at bedtime [4]

• Consider addition of H2 antagonist to H1 anti-histamines

• Omalizumab: second-line treatment; efficacy demonstrated, especially in  dermographism, cold, delayed pressure and solar urticarias [21]

• Delayed pressure urticaria/angioedema: may be less H1 anti-histamine responsive; addition of montelukast may be beneficial [22]

• Cholinergic urticaria: consider hydroxyzine in cases refractory to second generation H1 anti-histamines; anabolic steroids (danazol, stanazolol) have also been used but have significant side effects [23]

• Cyproheptadine previously used for cold urticaria, but has not demonstrated  superiority compared to other anti-histamines [24] 

Third line systemic treatments:

• Glucocorticoids, phototherapy, cyclosporin, ketotifen, plasmapheresis, doxepin,  dapsone, IVIG, sulfasalazine, theophylline, TNF antagonists, IL-1 antagonists,  antibiotics may be considered in select cases where disease is refractory to other  treatments, but have side effects [9]

• Cholinergic urticaria: propranolol, botox, scopolamine, methantheliniumbromide have been used [4, 5, 9]

• Solar urticaria: afamelanotide (melanocortin-1 receptor agonist) can be helpful for solar urticaria [9] 

Therapies in development for CIndU

• dupilumab: monoclonal antibody targeting interleukin-4 (IL-4) and interleukin-13 (IL-13)

  • Case series with solar urticaria with who was omalizumab resistant [25]

  • Two case reports with cold induced urticaria with resolution [26]

• remiburtinib: BTK inhibitor

  • A phase III randomized clinical trials investigating remibrutinib efficacy in patients with symptatic dermatographism, cold induced urticaria and cholinergic urticaria [27]

• anti-c-KIT

• barzolizumab

• Phase II studies in CIndU are currently ongoing [28] 

• briquilimab 

  • also be evaluated in CIndU [28]

• IgE-Trap protein (YH35324) 

  • High affinity for IgE

  • Currently in phase I trial for cold induced urticaria [29]

Desensitization: may be possible, although is not curative and requires consistent  exposure to maintain desensitized state; procedure should be done under supervision of a  specialist equipped to treat systemic reactions due to possibility of inducing anaphylaxis

• Cholinergic: may have a latency period up to 24H after an episode, with reports of  desensitization by routine exercise, autologous sweat [9] 

• Cold: daily cold showers; beginning above temperature threshold - repeated  exposure of increasingly larger skin areas to progressively colder water