What are halogenodermas?
Halogenodermas are rare skin reactions related to high levels of halogens in the body. Halogens are a group of natural elements with similar chemical properties. Examples of clinically relevant halogens are bromine and iodine, and when these are part of compounds, such as medications, they are called bromides and iodides. The skin eruption may be named for the specific halogen involved, ie, bromoderma and iododerma respectively.
Who gets a halogenoderma?
Bromine and bromides
Bromides have been widely used orally as sedatives, anti-epileptics, anti-neoplastics (chemotherapy), spasmolytics (used for colic) and expectorants (cough medicine).
Bromide may still be prescribed in:
- Carbromalhydroxyzine hydrochloride (short acting sedative)
- Pipobroman (alkylating agent for myeloproliferative disorders, e.g., some types of leukaemia)
- Potassium bromide (for epilepsy)
- Ipratropium bromide (bronchodilator)
- Dextromethorphan hydrobromide (antitussive in cough mixtures)
- Scopolamine bromide (to treat colic in infants).
Bromoderma has been reported in breastfed infants when the mother was taking a bromine-containing medication.
Bromine intoxication may occur in 1–10% of exposed patients.
Citrus-flavoured soft drinks may contain brominated vegetable oil as an emulsifier and flavour carrier. Excessive consumption of cola drinks and ‘Ruby Red Squirt’ have been reported to cause bromoderma.
Other sources of bromine have included the pesticide methyl bromide, brominated spa pool disinfectants, flame retardants, permanent hair wave solutions and silver bromide used in photographic films/papers.
Iodine and iodides
Iodine is used topically, orally and by injection.
Iodine is commonly used in topical antiseptics and there have been rare reports of iododerma following prolonged use of iodine-containing antiseptics applied to large areas of broken skin, eg, to burns and following surgery where the wound has been left open to heal.
Oral iodine is used in the treatment of some thyroid diseases, and potassium iodide for the skin diseases erythema nodosum and sporotrichosis. It is found in some expectorants, multivitamins and tonics. Amiodarone, a medication used to treat angina and heart arrhythmias (palpitations), has rarely been reported to cause iododerma after 18–24 months of use. Iodine may also be ingested in high-iodine containing foods such as seaweed, seafood and iodised salt, with rare cases of iododerma reported following prolonged and excessive ingestion.
Iodine is used as a radiocontrast medium for x-rays including CT scan, cholecystogram and pyelogram, either orally or by injection into the bloodstream. However most of the iodine administered this way would usually be excreted by the kidneys within 24 hours of administration.
The amount of iodine required to cause an iododerma reaction is variable.
Accumulation of the halogen in the body seems to be required for this reaction so it usually occurs with:
- Prolonged or excessive use, and/or
- Acute or chronic kidney failure, as halogens are excreted from the body by the kidneys.
A possible association has been suggested between halogenoderma and polyarteritis nodosa or myeloproliferative disorders such as multiple myeloma.
Proposed mechanisms for halogenoderma
Several theories have been put forward to explain the development of halogenoderma.
- Delayed hypersensitivity reaction/allergic reaction. Iodine binds to protein in the bloodstream and it is believed that an allergic reaction develops against this complex. Lymphocyte transformation tests with iodinated human serum albumin have been positive in some cases.
- Excretion of halogen via sweat or oil glands may result in an inflammatory reaction in the skin.
- Halogens may make usually non-pathogenic or harmless skin microorganisms pathogenic.
Clinical features of halogenoderma
Generally, it takes months of continuous exposure to a halogen in order to develop a halogenoderma. However, in some cases it can be acute within days, particularly following administration of iodine-containing radiocontrast medium for x-rays in patients with kidney failure.
Lesions most commonly appear on the face and upper body, but involvement of the limbs and mucous membranes (mouth, conjunctiva of the eye) can also occur.
There are a number of clinical presentations of halogenodermas:
- Acne-like rash – pustules and small red lumps (acne medicamentosa)
- Vegetating/fungating nodules – raised firm lumps
- Exudative plaques – weepy, slightly raised, large areas
- Vegetating or necrotic ulcer with pustules
- Blisters – small or large; clear, pus- or blood-filled
- Tuberous bromoderma – occurs mainly in infants and starts as small red bumps or pustules that rapidly merge into a raised plaque, most commonly on face, scalp and legs
- Halogen panniculitis (inflammation of fat) – tender red swellings under the skin usually 1-2 cm in diameter, but can be up to 10 cm. Abscesses form that may ulcerate and scar. This is part of a systemic illness, initially with fever and diarrhoea, but with continued halogen exposure abdominal and muscle pain develop, as well as worsening of the initial symptoms.
More than one of these skin patterns may occur in an individual. Lesions such as ulcers and plaques may be solitary or multiple.
Swelling of the major salivary glands (parotid, submandibular) has been reported following iodine-containing contrast medium and has been called ‘iodine mumps’.
Rarely there may also be systemic symptoms and signs of halogen toxicity. Bromism includes muscle weakness, personality changes, abnormal walking gait and fits. Toxic effects of iodine include low blood pressure and slow heart rate, kidney failure, inflammation of small blood vessels (leukocytoclastic vasculitis), overactive thyroid and abnormal liver function.
How is the diagnosis of halogenoderma made?
A diagnosis of halogenoderma is usually made on the basis of:
- History of halogen exposure
- Clinical features
- Histopathology of a skin biopsy. Skin biopsy shows neutrophil white cells with eosinophils and lymphocytes in the epidermis forming small abscesses. There may also be some inflammation in the dermis and involving blood vessels. Bromoderma also tends to show thickening of the epidermis (pseudoepitheliomatous hyperplasia).
- Blood tests, which may confirm the high halogen level.
However none of these tests are diagnostic and it is the combination that makes the diagnosis.
Treatment of halogenoderma
Stopping the halogen will generally result in resolution over 4–6 weeks. Bromide has a long half-life in the body, about 12 days, so it takes some time for the blood level to fall. The clinical improvement parallels the falling blood level of halogen.
Wound care may be required for ulcers.
Sometimes active treatment may also be required, including fluid tablets (e.g. frusemide or ethacrynic acid) or intravenous fluids to increase excretion of the halogen by the kidneys, and/or anti-inflammatory medications, such as topical or oral corticosteroids or oral ciclosporin.
Mild postinflammatory pigmentation or scarring may persist after the skin lesions have healed. Very rarely, halogenoderma may be fatal.