Dermatitis herpetiformis and iodine

E Besnier et al. found in 1892 that the ingestion of iodides caused hypersensitivity reactions in patients with dermatitis herpetiformis (DhD). Subsequent studies confirmed the observation that orally administered potassium iodide led to an exacerbation of dermatitis herpetiformis. The first use of the potassium iodide patch test for the differential diagnosis of dermatitis herpetiformis was made in 1912 by J. Jadassohn. In the following ten years, many researchers confirmed the existence of this hypersensitivity in DhD patients to the external application of halides as well as to their ingestion. In 1925, M. Jessner et al. reported that patients with dermatitis herpetiformis reacted not only to potassium iodide but also to potassium bromide applied topically and administered orally. They emphasized that these tests are valuable for distinguishing between dermatitis herpetiformis and pemphigus and other bullous rashes.

Potassium iodide (KI) when applied topically to non-lesional skin leads to vesicular lesions with perivascular cellular infiltrates similar to those seen in spontaneously occurring lesions. The progression of the lesions is AI concentration-dependent. Furthermore, the enzymatic activity of TG3 in the IgA deposits of DH skin was shown to be directly dependent on the KI concentration. Interestingly, the 1 M and 2 M KI sections also showed staining in the basal and prickle cell layer of the epidermis. Three other members of the TG family are expressed in the different layers of the epidermis and would also be targets for KI in addition to TG3. It is hypothesized that the increase in TG3 activity could be reversed by removing the potassium iodide and allowing time for the hydrophobic effect to increase in order to refold the enzyme and thus slow down its activity. Semi-quantitative measurements showed that the slides washed for 15 minutes had less than 20% of the staining seen in the positive KI control, and the slides washed for 30 minutes had minimal to no staining.

The active site of TG3 in the IgA deposits of DH skin is conformationally altered by high concentrations of calcium iodide. This enables increased activity of the enzyme. In fact, this regulation is due to reversible steric changes.

Clinically, the condition of DH patients worsens dramatically when they take iodide in commercially available preparations (e.g. KI as an expectorant). The clinical deterioration of DH in response to KI and the KI patch test is thought to be directly dependent on TG3 activity. The delay of 12 to 24 hours observed in the clinical response to the patch test can be explained by the time required for skin absorption of KI and the formation of lesions.

1. Alcon DN (1947) Sensitivity to iodides and bromides in dermatoses other than dermatitis herpetiformis. J Invest Dermatol 8:287-290.
2. Antiga E et al (2019) Dermatitis Herpetiformis: Novel Perspectives. Front Immunol 10:1290.
3. Besnier E et al. (1892) Handb. d. Haut-u. Geschlechtskr. VII/2: P 592.
4. Boenrieder T et al. (2003) From the New World. Louis A. Duhring and Dermatitis Herpetiformis. Dermatologist 54: 167-172
5. Collin P et al. (2017) Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease. Ann Med 49:23-31.
6. Collin P, Reunala T (2003) Recognition and management of the cutaneous manifestations of celiac disease: a guide for dermatologists. Am J Clin Dermatol 4: 13-20
7. Cynkier A et al. (2012) Expression of selected neuropeptides in pathogenesis of bullous pemphigoid and dermatitis herpetiformis. Pol J Pathol 63:31-39.
8. Danlos AN (1889) Dermatite herpétiforme aigue consecutive l'emploi de l'iodine de potasse. Soc. franc dermatol. Ann dermatol syph 1898: 1006.

9. Spier HW et al. (1952) On the question of iodine sensitivity in dermatitis herpetiformis Duhring; the epicutaneous iodine potassium test as a non-specific Hofmeister anion effect. Arch Dermatol Syph 195:105-137.

10. Taylor TB et al (2018) Sensitivity of Transglutaminase 3 in the IgA Aggregates in Dermatitis Herpetiformis Skin to Potassium Iodide. J Invest Dermatol 138:2066-2068.