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 Table of Contents  
LETTER TO EDITOR
Year : 2019  |  Volume : 5  |  Issue : 1  |  Page : 59-62

Potassium iodide: A prodigy in the treatment of subcutaneous zygomycosis


Department of Skin and STD, Vinayaka Mission's Kirupananda Variyar Medical College and Hospitals, Vinayaka Mission's Research Foundation (Deemed to be University), Salem, Tamil Nadu, India

Date of Web Publication22-Jul-2019

Correspondence Address:
Dr. Seethalakshmi Ganga Vellaisamy
No: 11, Mullai Nagar, Near Chandra Mahal, Seelanaickenpatti, Salem - 636 201, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_10_19

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How to cite this article:
Nalini P, Vellaisamy SG, Manickam N, Gopalan K. Potassium iodide: A prodigy in the treatment of subcutaneous zygomycosis. Indian J Drugs Dermatol 2019;5:59-62

How to cite this URL:
Nalini P, Vellaisamy SG, Manickam N, Gopalan K. Potassium iodide: A prodigy in the treatment of subcutaneous zygomycosis. Indian J Drugs Dermatol [serial online] 2019 [cited 2019 Sep 18];5:59-62. Available from: http://www.ijdd.in/text.asp?2019/5/1/59/263087



Sir,

Subcutaneous zygomycosis (subcutaneous phycomycosis) is one of the deep fungal infections caused by a member of fungi belonging to the class zygomycetes, order Entomophthorales, genera Basidiobolus, and Conidiobolus. It is also caused by species of Absidia, Rhizopus, Mortierella, and Hypomyces destruens.[1] It is a granulomatous infection of the skin and subcutaneous tissues characterized by the formation of firm, nontender swelling on the extremities and trunk.[1] Usually, it is seen in early childhood.[2] Oral potassium iodide (KI) is considered as gold standard in the treatment of subcutaneous zygomycosis. In India, so far, only a few cases have been reported. We present a rare case of subcutaneous zygomycosis in an adult male who showed dramatic response with oral KI alone.

A 75-year-old man presented with a diffuse asymptomatic swelling over left forearm and arm of 6 months' duration. It started as a small swelling in the left arm, gradually increasing in size and extending to forearm. There was no history of trauma or surgery before the onset of swelling. Dermatological examination showed well-demarcated, indurated, firm, painless swelling of size 12 cm × 11.5 cm involving extensor aspect of the left forearm and arm [Figure 1]. The margin was well-defined, and finger insinuation test was positive [Figure 2]. The skin was hyperpigmented and nonpinchable. There was no associated lymphadenopathy.
Figure 1: Well-demarcated swelling over extensor aspect of the left forearm and arm

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Figure 2: Positive finger insinuation test

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General and systemic examination was within normal limits. We considered a differential diagnosis of soft-tissue tumor. Routine laboratory tests were within normal limits. X-ray of the left arm showed soft-tissue shadow without any bony involvement. Punch specimen was taken from the swelling; the tissue was cut into slices, crushed, and then examined under 10% potassium hydroxide which revealed fungal elements with broad aseptate hyphae [Figure 3]. Culture on Sabouraud's dextrose agar did not reveal any fungal colonies. Histopathology from the skin lesion showed a normal epidermis, numerous deep dermal, and subcutaneous foci of perivascular foam aggregates and few nonbranching, broad thin-walled hyphae. These hyphae stained positively with periodic acid–Schiff stain [Figure 4].
Figure 3: Potassium hydroxide mount showing fungal elements with broad aseptate hyphae

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Figure 4: Photomicrograph showing numerous deep and subcutaneous foam cell aggregates and few fungal hyphae (H and E, ×100)

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Based on the clinical, microbiological, and histopathological findings, a diagnosis of subcutaneous phycomycosis was made. All the baseline investigations, including thyroid function test, were found to be within normal limits, and the patient was started on freshly prepared saturated solution of KI (SSKI). It was prepared by adding 10 g of KI to 10 ml of distilled water in a tight, light-resistant container, which contains approximately 65 mg per drop of SSKI. He was started with five drops of KI three times a day according to the weight of the patient, in a glass of water. Both size and induration of the swelling gradually decreased in size after 2 months of treatment [Figure 5]. The dose of KI was tapered to three drops three times a day for 1 month. There was a complete resolution of the lesion at the end the 3rd month, so we tapered the dose of KI to one drop three times a day for 1 month, and we stopped the drug after that. Thyroid function test was done at the end of the 3rd month, and it was found to be normal. The patient is still on our follow-up, and he did not show any signs and symptoms of recurrence even after 1 year of stopping KI.
Figure 5: Complete resolution after 3 months of treatment

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Subcutaneous phycomycosis was first described in Indonesia in the year 1956.[1] The class zygomycetes include two fungal orders, Mucorales and Entomophthorales, with extremely different pathogenic potentials. Mucorales affect only the immunocompromised patient causing mortality in excess of 60% in those affected, while Entomophthorales, which include Basidiobolus and Conidiobolus genera, affect the immune-competent individual, causing principally chronic infection of the subcutaneous tissue.[2]Basidiobolus ranarum is a saprophytic fungus which is present in the soil, decaying fruit, vegetable matter, and also in the gut of amphibians and reptiles. It can cause a variety of clinical manifestations including subcutaneous zygomycosis, gastrointestinal zygomycosis, and occasionally an acute systemic illness. Subcutaneous zygomycosis is the most common clinical form of basidiobolomycosis and is endemic in South India.

Implantation after trauma is probably the mode of entry like in other subcutaneous mycoses. In the past, clinical isolates of Basidiobolus were classified as B. ranarum, B. meristosporus, and B. haptosporus. However, recent taxonomic studies indicate that all human pathogens belong to B. ranarum.[3] It is a granulomatous infection of the skin and subcutaneous tissues characterized by firm and nontender swellings, commonly on the extremities, trunk, and rarely other parts of the body.[4] The disease usually occurs in children, less often in adolescents and rarely in adults.[4] However, in our patient, zygomycosis was seen in an elderly male in contrast to previous studies which has been rarely reported so far. Males are more commonly affected than females.[4] Entomophthoromycosis is a potentially curable disease which can masquerade as a neoplasm. In our case also, the duration and the clinical presentation of the swelling, misguided the clinician to diagnose it as a soft-tissue tumor. Always a high index of suspicion is needed to diagnose such cases, thereby avoiding unnecessary excision which may hasten the spread of infection as observed by Prasad et al.[5]

KI is considered as the gold standard in cases of entomophthoromycosis and supposed to get localized at the sites where the organisms are present. It is said to enhance the proteolytic activity of myeloperoxidase enzyme system of the neutrophils.[6] 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. 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.[7] The response to KI is dramatic and complete as evidenced in our case.

KI is medicinally supplied in 130 mg tablets for emergency purposes. KI may also be administered as a “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 United States Pharmacopeia formulation. SSKI should be stored in tight, light-resistant containers at a temperature of 15°C–30°C. Crystallization may occur following exposure to cold. Crystals dissolve with warming and shaking of solution.[7]

KI is well-absorbed orally and distributed selectively into the thyroid gland. It also distributes to a minor extent into the salivary glands, breast, choroid plexus, and gastric mucosa. It is not concentrated in the thyroid gland and is excreted mainly in urine.[7] It has been successfully used in cases of sporotrichosis, human pythiosis, Nocardia brasiliensis, cutaneous cryptococcosis, rhinophycomycosis, panniculitis, neutrophilic dermatoses, Wegener's granulomatosis, erythema multiforme, Behcet's syndrome, and disseminated granuloma annulare. Contraindications include known hypersensitivity to KI, hypocomplementemic vasculitis, dermatitis herpetiformis, nodular thyroid diseases (e.g., multinodular goiter), and active tuberculosis.[7]

Common side effects include stomach upset, diarrhea, nausea, vomiting, and 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. 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 the drug. Abundant fluid and salt intake may help eliminate iodide.[7]

Hypersensitivity reactions – angioedema, cutaneous and mucosal hemorrhage, signs and symptoms resembling serum sickness (e.g., fever, arthralgias, lymph node enlargement, and eosinophilia) – may occur. Urticaria, thrombotic thrombocytopenic purpura, and fatal periarteritis may occur. Patients with hypocomplementemic vasculitis associated with chronic urticaria or systemic lupus erythematosus are at an increased risk of developing a severe systemic illness. If hypersensitivity occurs, discontinue therapy. Cutaneous side effects – these include (a) acneiform eruption; (b) iododermas – erythematous, vesicular, bullous, urticarial, nodular, or vegetating lesions on face, shoulder, and extremities; (c) aggravation of dermatitis herpetiformis; (d) periarteritis nodosa; (e) pustular psoriasis; and (f) granulomatous vasculitis.[7]

KI is given in the dose of 40–60 mg/kg body weight. A total dose of up to 3 g/day can be given. It has to be given for months to years or 1 month following complete resolution of the lesion. Other drugs found to be useful are azole antifungals such as ketoconazole 4 mg/kg, fluconazole or itraconazole 3–6 mg/kg. Itraconazole seems to have a high concentration in subcutaneous tissue. In widespread infection, injection amphotericin B is the drug of choice.[6]

Many Indian case reports[5],[8],[9] have suggested that most of the patients of subcutaneous zygomycosis respond excellently to potassium iodide alone as monotherapy which is well evidenced in our patient also.

We are presenting this case of subcutaneous phycomycosis for its excellent response to potassium iodide alone which is a cheap treatment modality. A high index of suspicion and awareness about this condition is necessary to avoid misdiagnosis and unnecessary surgical intervention. Timely diagnosis is important to avoid the disfigurement caused by advanced disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Burkitt DP, Wilson AM, Jelliffe DB. Subcutaneous Phycomycosis: A review of 31 cases seen in Uganda. Br Med J 1964;1:1669-72.  Back to cited text no. 1
    
2.
Prabhu RM, Patel R. Mucormycosis and entomophthoramycosis: A review of the clinical manifestations, diagnosis and treatment. Clin Microbiol Infect 2004;10 Suppl 1:31-47.  Back to cited text no. 2
    
3.
Sujatha S, Sheeladevi C, Khyriem AB, Parija SC, Thappa DM. Subcutaneous zygomycosis caused by Basidiobolus ranarum – A case report. Indian J Med Microbiol 2003;21:205-6.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Gugnani HC. A review of zygomycosis due to Basidiobolus ranarum. Eur J Epidemiol 1999;15:923-9.  Back to cited text no. 4
    
5.
Prasad PV, Paul EK, George RV, Ambujam S, Viswanthan P. Subcutaneous phycomycosis in a child. Indian J Dermatol Venereol Leprol 2002;68:303-4.  Back to cited text no. 5
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6.
Krishnan SG, Sentamilselvi G, Kamalam A, Das KA, Janaki C. Entomophthoromycosis in India – A 4-year study. Mycoses 1998;41:55-8.  Back to cited text no. 6
    
7.
Hassan I, Keen A. Potassium iodide in dermatology. Indian J Dermatol Venereol Leprol 2012;78:390-3.  Back to cited text no. 7
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8.
Anaparthy UR, Deepika G. A case of subcutaneous zygomycosis. Indian Dermatol Online J 2014;5:51-4.  Back to cited text no. 8
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9.
Mondal AK, Saha A, Seth J, Mukherjee S. Subcutaneous zygomycosis: A Report of one case responding excellently to potassium iodide. Indian J Dermatol 2015;60:500-2.  Back to cited text no. 9
[PUBMED]  [Full text]  


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