Potassium iodide in dermatology

Iffat Hassan, Abid Keen

 Department of Dermatology, STD and Leprosy, Government Medical College and Associated SMHS Hospital, Srinagar, Jammu and Kashmir, India

Correspondence Address:
Iffat Hassan
House No: 35, Mominabad, Hyderpora, Srinagar, Jammu and Kashmir - 190 014
India

Introduction

"Because the newer methods of treatment are good, it does not follow that the old ones are bad: For if our honorable and worshipful ancestors had not recovered from their ailments, you and I would not be here today" . [Confucius]

Iodine was first discovered in seaweeds about two centuries ago and was used medically for a variety of conditions such as thyroid disorders, syphilis, psoriasis and atopic dermatitis. It is most conventionally used as a saturated solution of potassium iodide (KI).

KI has been primarily used in the treatment of endemic goiter and is usually given for this purpose as iodized salt. Other indications include treatment of hyperthyroidism, radiation protectant of thyroid gland and preoperative preparation of patients with Grave′s disease. It is also used for the treatment of some dermatological conditions such as cutaneous sporotrichosis and various inflammatory dermatoses.

Pharmacology

KI is medicinally supplied in 130 mg tablets for emergency purposes. KI may also be administered as a "saturated solution of potassium iodide " (SSKI) which contains 1000 mg of KI per ml of solution. Each drop of SSKI is assumed to contain about 50 mg iodine as iodide. In order to prepare SSKI, KI is added to hot purified water, using sodium thiosulphate as a preservative. Since the solubility of KI in water at room temperature is about 1.40-1.48 g/ml pure water, and the resulting solution has a density of about 1.72 g/ml, this process also results in a final concentration of KI of about 1000 mg KI/ml of saturated KI solution, and also contains essentially the same concentration of iodide per drop as does the U.S.P. formulation. KI solution is usually added to water, fruit juice or milk before drinking in order to prevent gastrointestinal irritation. SSKI should be stored in tight, light-resistant containers at a temperature of 15-30°C. Crystallization may occur following exposure to cold. Crystals dissolve with warming and shaking of solution. The color of KI solution in water is bright yellow. If the solution turns brownish yellow, it should be discarded.

KI is well absorbed orally and distributed selectively into thyroid gland. It also distributes to a minor extent into the salivary glands, breast, choroid plexus and gastric mucosa. It readily crosses the placenta and is distributed into milk. It is not concentrated in the thyroid gland and is excreted mainly in urine.

Mechanism of Action

The exact mechanism of action of KI in dermatological diseases is not known. Since KI appears to be particularly effective in those conditions where neutrophils predominate, it was speculated that it acts because of its effects on neutrophils. In 1982, Miyachi and Niwa noted that KI suppresses the ability of the neutrophils to generate the toxic oxygen intermediates hydrogen peroxide and hydroxyl radicals in vitro. ^[1] Honna et al., in 1990 found that KI has an inhibitory effect on neutrophilic chemotaxis. ^[2]

The mode of action of KI on various fungi has not yet been established. The direct action of KI on the fungus has been denied and the activation of macrophages by iodine has now been assumed to be responsible for the healing effect. KI apparently does not have a direct action on Sporothrix Schenckii. The spontaneous healing and the variability of the clinical presentation in the disease have strengthened the idea that KI rather interacts with the immune response of the host.

Indications

Sporotrichosis

KI was first used in early 20 ^th century for this condition and continues to be used even today because of its effectiveness and low cost. It has shown good results in the treatment of fixed cutaneous sporotrichosis and lymphocutaneous sporotrichosis. ^[3],[4],[5]

For adults, initially, 250 mg (approximately 5 drops of a 1-g/ml solution) is administered three times a day. ^[6] Gradually the dosage is increased as tolerated to a maximum of 2-2.5 g (approximately 40-50 drops of a 1 g/ml solution) three times daily for 6-10 weeks. ^[7]

Treatment with KI should be stopped if signs of iodism appear or a hypersensitivity develops to KI. In children, a maximum of 1.25-2 g (approximately 25-50 drops of a 1-g/ml solution) is administered thrice a day. ^[8],[9] Once daily dose is as efficacious as three times dosing and has an improved compliance, especially in children for the treatment of sporotrichosis. ^[10]

However, where available, Itraconazole has replaced KI use for the treatment of sporotrichosis. ^[11],[12] KI is considered as an alternative therapy because of the problems with long-term compliance (i.e, numerous side effects, lack of solid oral dosage form). KI has not been found to be effective for the treatment of extracutaneous (pulmonary, extraarticular, meningeal) sporotrichosis or disseminated sporotrichosis. Amphotericin B or Itraconazole are considered the drugs of choice for these forms of sporotrichosis.

Other varieties of subcutaneous mycosis

KI has been successfully used in cases of subcutaneous phycomycosis, ^{[13],[14],[15]} human pythiosis, ^[16] nocardia brasiliensis, ^[17] cutaneous cryptococcosis ^[18] and rhinoentomophthoromycosis ^[19] (rhinophycomycosis).

Panniculitis

KI has been found to be effective in erythema nodosum and nodular vasculitis. ^{[20],[21],[22]} The adult dosage of KI in these disorders is 300-900 mg per day. Relief of symptoms such as local tenderness, fever and arthralgias occurs within 24-48 hrs while as the clearing of lesions occurs within a period of 10-14 days.

A rapid response to KI has also been reported in cases of subacute nodular migratory panniculitis (erythema nodosum migrans). ^[23],[24]

Neutrophilic dermatoses

KI has also been tried in Sweet′s syndrome ^[25] and pyoderma gangrenosum. Sanburg and Benzie described a patient with Crohn′s disease and pyoderma gangrenosum whose skin lesions healed after KI treatment. ^[26] Richardson and Callen also showed its effectiveness for the treatment of recalcitrant pyoderma gangrenosum. ^[27] In these conditions, KI has been found to be effective in a dose of 300 mg three times a day. KI should be used as an alternate choice for the treatment of neutrophilic dermatoses when other treatments fail, are contraindicated, or cause intolerable side effects.

Wegener′s granulomatosis

Corticosteroids when used in combination with KI (800 mg per day) cause a rapid resolution and clearing of lesions within 3 months. ^[28]

Miscellaneous uses

Other dermatological conditions where KI has been found to be useful include erythema multiforme, Behcet′s syndrome, disseminated granuloma annulare. ^[29]

Side Effects

1. Common side effects include stomach upset, diarrhea, nausea, vomiting, stomach pain. These acute side effects go away during treatment as the body adjusts to the medicine or can be lessened by avoiding rapid dosage increases. Other less common side effects include urticaria and angioedema.
2. Iodism:- Iodism (chronic iodine poisoning) may occur following long - term therapy or with the use of high dosages. Manifestations include burning in the mouth or throat, severe headache, metallic taste, soreness of teeth and gums, coryza, sneezing, eye irritation with eyelid swelling, unusual increase in salivation, confusion, arrhythmias, numbness and weakness. If manifestations of iodism occur, discontinue KI and initiate appropriate supportive therapy. Symptoms usually resolve soon after the discontinuation of drug. Abundant fluid and salt intake may help eliminate iodide.
3. Productive cough, pulmonary edema, swelling/tenderness of parotid and submaxillary glands, inflammation of pharynx/larynx/tonsil may occur. ^[30]
4. Hypersensitivity reactions:- Angioedema, cutaneous and mucosal hemorrhage, signs and symptoms resembling serum sickness (e.g, fever, arthralgias, lymph node enlargement, eosinophilia) may occur. Urticaria, thrombotic thrombocytopenic purpura and fatal periarteritis may occur. Patients with hypocomplementemic vasculitis associated with chronic urticaria or SLE are at an increased risk of developing severe systemic illness. ^[31] If hypersensitivity occurs, discontinue therapy.
5. Cutaneous side effects:- These include: a) Acneiform eruption b) Iododermas ^[32] - erythematous, vesicular, bullous, urticarial, nodular or vegetating lesions on face, shoulder and extremities c) Aggravation of dermatitis herpetiformis. ^[33]
6. Rare side effects:- a) Periarteritis nodosa ^[34] e) Pustular psoriasis ^[35] and f) Granulomatous vasculitis. ^[36]

Drug Interactions

ACE inhibitors :- Hyperkalemias, cardiac arrhythmias, cardiac arrest.

Antithyroid drugs:- Possible potentiation of hypothyroid and goitrogenic effects of antithyroid drugs.

Potassium sparing diuretics:- Hyperkalemia, cardiac arrhythmias, cardiac arrest.

Lithium:- Possible additive or synergistic hypothyroid effects.

Amiodarone and sulphonamides:- Potentiation of hypothyroidism.

Special Situations

1. Pregnancy:- KI is a pregnancy category D drug. Short-term therapy is used by some clinicians without any evidence of adverse fetal effects. Long-term therapy is considered by most clinicians to be contraindicated. ^[37]
2. Lactation:- Since KI is distributed into milk, a possible rash and thyroid suppression in infants can occur. AAP considers KI to be compatible with breast feeding. ^[38]
3. Patients with alteration in thyroid function:- Long-term use with KI may induce hyperthyroidism or hypothyroidism. ^[39],[40] So caution is warranted while administrating KI in patients with pre-existing thyroid disorders (multinodular goiter, Grave′s disease, autoimmune thyroiditis).
4. Concomitant illness:- KI should be used with caution in patients with Addison′s disease, cardiac disease, myotonia congenita or renal impairment.

Contraindications

1. Known hypersensitivity to KI.
2. Hypocomplementemic vasculitis. ^[31]
3. Dermatitis herpetiformis. ^[33]
4. Nodular thyroid diseases (e.g, multinodular goiter) ^[39]
5. Active tuberculosis.

1.	Miyachi Y, Niwa Y. Effect of potassium iodide, colchicines and Dapsone on the generation of polymorphonuclear leukocyte- derived oxygen intermediates. Br J Dermatol 1982;107:209-14. [Google Scholar]
2.	Honna K, Saga K, Onodera H, Takahashi M. Potassium iodide inhibits neutrophil chemotaxis. Acta Derm Venereol 1990;70:247-9. [Google Scholar]
3.	Sterling JB, Heymann WR. Potassium iodide in dermatology: A 19 th century drug for the 21 st century- Uses, pharmacology, adverse effects, and contraindications. J Am Acad Dermatol 2000;43:691-7. [Google Scholar]
4.	Agarwal S, Gopal K, Umesh, Kumar B. Sporotrichosis in Uttarak hand (India): A report of nine cases. Int J Dermatol 2008;47:367-71. [Google Scholar]
5.	Mahajan VK, Sharma NL, Sharma RC, Gupta ML, Garg G, Kanga AK. Cutaneous sporotrichosis in Himachal Pradesh, India. Mycosis 2005;48:25-31. [Google Scholar]
6.	Kauffman CA. Sporotrichosis. Clin Infect Dis 1999;29:231-7. [Google Scholar]
7.	Kauffman CA, Hajjeh R, Chapman SW. Practice guidelines for the management of of patients with sporotrichosis. For the Mycosis Study Group. Infectious Diseases Society of America. Clin Infect Dis 2000;30:684-7. [Google Scholar]
8.	Restrepo A. Treatment of tropical mycosis. J Am Acad Dermatol 1994;31:59-102. [Google Scholar]
9.	Bonifaz A, Saul A, Paredes-Solis V, Fierro L, Rosales A, Palacios C, et al. Sporotrichosis in childhood: Clinical and therapeutic experience in 25 patients. Pediatr Dermatol 2007;24:369-72. [Google Scholar]
10.	Cabezas C, Bustamante B, Holgado W, Begue RE. Treatment of cutaneous sporotrichosis with one daily dose of potassium iodide. Pediatr Infect Dis J 1996;15:352-4. [Google Scholar]
11.	Morris-Jones R. Sporotrichosis. Clin Exp Dermatol 2002;27:427-31. [Google Scholar]
12.	Houh W, Chung SR, Ro BI. Itraconazole in the treatment of sporotrichosis: A Korean experience. Trop Doct 1995;25:107-9. [Google Scholar]
13.	Burkitt DP, Wilson AM, Jelliffe DB. Subcutaneous phycomycosis. A review of 31 cases seen in Uganda. BMJ 1964;1:1669-72. [Google Scholar]
14.	Prasad PV, Paul EK, George RV, Ambujan S, Viswanthan P. Subcutaneous phycomycosis in a child. Indian J Dermatol Venereol Leprol 2002;68:303-4. [Google Scholar]
15.	Goyal A, Gupta N, Das S, Jain S. Basidiobolomycosis of the nose and face: A case report and a mini-review of unusual cases of basidiobolomycosis. Mycopathologia 2010;170:165-8. [Google Scholar]
16.	Imwidthaya P. Human pythiosis in Thailand. Postgrad Med J 1994;70:558-60. [Google Scholar]
17.	Mitchell G, Wells GM, Goodman JS. Sporotrichoid Nocardia brasiliensis infection: Response to potassium iodide. Am Rev Respir Dis 1975;112:721-3. [Google Scholar]
18.	Carrick L. Cutaneous cryptococcosis. AMA Arch Dermatol 1957;76:777-8. [Google Scholar]
19.	Bhatia N, Singh C, Kawatra R, Alam S, Dhawan R. Rhinoentomophthoromycosis: Rarity revisited. Ear Nose Throat J 2010;89:268-71. [Google Scholar]
20.	Horio T, Danno K, Okamoto H, Miyachi Y, Imamura S. Potassium iodide in erythema nodosum and other erythematous dermatosis. J Am Acad Dermatol 1983;9:77-81. [Google Scholar]
21.	Schultz EJ, Whiting DA. Treatment of erythema nodosum and nodular vasculitis with potassium iodide. Br J Dermatol 1976;94:75-8. [Google Scholar]
22.	Horio T, Imamura S, Danno K, Ofuji S. Potassium iodide in the treatment of erythema nodosum and nodular vasculitis. Arch Dermatol 1981;117:29-31. [Google Scholar]
23.	Rotas A, Lowe D, Smout M. Erythema nodosum migrans in a young woman. Arch Dermatol 1980;116:325-6. [Google Scholar]
24.	Vilanova X, Aguade JP. Subacute nodular migratory panniculitis. Br J Dermatol 1959;71:45-50. [Google Scholar]
25.	Myatt AE, Baker DJ, Byfield DM. Sweet's syndrome: A report on the use of potassium iodide. Clin Exp Dermatol 1987;12:345-9. [Google Scholar]
26.	Sanburg AL, Benzie JL. An unusual use of an old drug. Potassium iodide in pyoderma gangrenosum. Aust J Hosp Pharm 1987;17:187-8. [Google Scholar]
27.	Richardson JB, Callen JP. Pyoderma gangrenosum treated successfully with potassium iodide. J Am Acad Dermatol 1993;28:1005-7. [Google Scholar]
28.	Torinuki W. Wegener's granulomatosis successfully treated with prednisolone and potassium iodide. J Dermatol 1994;21:693-5. [Google Scholar]
29.	Smith JB, Hansen CD, Zone JJ. Potassium iodide in the treatment of disseminated granuloma annulare. J Am Acad Dermatol 1994;30:791-2. [Google Scholar]
30.	Munoz FJ, Bellido J, Moyano JC, Alvarez MJ, Juan JL. Adverse reactions to potassium iodide from cough syrup. Allergy 1997;52:1112-2. [Google Scholar]
31.	Curd JG, Milgrom H, Stevenson DD, Mathinson DA, Vaughan JH. Potassium iodide sensitivity in four people with hypocomplementemic vasculitis. Ann Intern Med 1979;91:853-7. [Google Scholar]
32.	Alpay K, Kurkcuoglu N. Iododerma: An unusual side effect of iodide ingestion. Pediatr Dermatol 1996;13:51-3. [Google Scholar]
33.	Reunala T. The role of diet in dermatitis herpetiformis. Curr Probl Dermatol 1991;20:168-75. [Google Scholar]
34.	Rasmussen H. Iodide hypersensitivity in the etiology of periarteritis nodosa. J Allergy 1995;26:394-407. [Google Scholar]
35.	Shelley WB. Generalized pustular psoriasis induced by potassium iodide: A postulated role for dihydrofolatec reductase. JAMA 1967;201:1009-14. [Google Scholar]
36.	Eeckhout E, Willemsen M, Deconinck A, Somers G. Granulomatous vasculitis as a complication of potassium iodide treatment for sweet's syndrome. Acta Derm Venereol 1987;67:362-4. [Google Scholar]
37.	Galina MP, Avnet NL, Einhorn A. Iodides during pregnancy: An apparent cause of neonatal death. N Engl J Med 1962;267:1124-7. [Google Scholar]
38.	Briggs GG, Freeman RK, Yaffe SJ. Potassium iodide. In: Briggs GG, Freeman RK, Yaffe SJ, editors. A reference guide to fetal and neonatal risk. Drugs in pregnancy and lactation. 7 th ed. Philadelphia: Lippincott Williams and Wilkins; 2005. p. 1326-7. [Google Scholar]
39.	Woeber KA. Iodine and thyroid disease. Med Clin North Am 1991;75:169-78. [Google Scholar]
40.	Heymann W. Potassium iodide and the wolff-chaikoff effect: Relevance for the dermatologist. J Am Acad Dermatol 2000;42:490-2. [Google Scholar]