Dermatology Online Journal

The use of recombinant human epidermal growth factor (rhEGF) in a gentleman with drug-induced Steven Johnson syndrome
Man Wo Tsang¹, Ka Yan Tsang¹, and Wan Keung R Wong²
Dermatology Online Journal 10 (1): 25

1. Department of Medicine & Geriatrics, United Christian Hospital, Hong Kong SAR, China2. Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water bay, Kowloon, Hong Kong

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Abstract

A case of drug-induced Steven Johnson syndrome in a gentleman is reported. Its course of treatment with rhEGF was compared to conventional treatment in historical control.

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Steven-Johnson syndrome (SJS) is a mucocutaneous drug-induced or idiopathic reaction characterised by erythema of skin and mucosa, and skin tenderness. Extensive cutaneous and mucosal exfoliation follows and this condition is potentially life threatening due to multi-system involvement. We report a case of SJS after exposure to NSAID and a remarkable response to a local application of recombinant human epidermal growth factor (rhEGF).

Report of case

In early 2003 a 79-year-old man was admitted through the emergency department of our hospital. He enjoyed good health and did not have a history of previous drug allergy. A few days prior to admission he suffered painful toes on the right foot and was treated with mefenamic acid for gout by his family doctor. Over the next 2-3 days he experienced pain in the oral cavity with desquamation of the lips and serosanguinous oozing. He was unable to eat solid food or drink liquids. He also noted blurring of vision and photophobia with tearing; he could not read the clock. In addition, he complained of dysuria and noticed multiple eroded lesions with discharge over the scrotum and penile tip.

On physical examination, he remained afebrile and his blood pressure was 110/60 mm Hg with a regular pulse of 90 beats per minute. A morbilliform and erythema multiforme-like rash with cutaneous sloughing was noted over the left axillary region and perioral areas (Fig. 1, 2). Crust formed over all the denuded areas. An ulcer-like lesion appeared over his scrotum and the tip of the penis (Fig.3). Bilateral conjunctival hyperemia with tears persisted (Fig. 4).

Figure 1	Figure 2

Figure 3	Figure 4

Figure 5

A complete blood count was normal as was the clotting profile. Renal function tests showed mild impairment with urea (13.2 mmol/l) and creatinine (136 µmol/l). Liver function tests and cardiac enzymes were both normal. An electrocardiogram and chest radiography were unremarkable. Examination of mid-stream urine was negative.

A diagnosis of Stevens-Johnson syndrome was made and he was put on intravenous fluid, corticosteroids, and piriton. A full eye assessment was made and Hypromellose™ eye drops and Solcoseryl™ eye gel were prescribed. Epidermal growth factor (rhEGF 0.02 %) was applied locally to the exfoliated lesions on the penis and scrotum; the left axillary region was treated with saline dressings. The next day the patient reported that the pain in the area of the external genitalia had markedly decreased and the rash improved. The patient requested that the rhEGF cream be applied to the left axillary area as well. On day 3 he was discharged and the eruption completely subsided by day 10. The rhEGF cream used for the treatment of SJS was prepared by the pharmacy department in our hospital by mixing freeze-dried rhEGF powder (0.02 %) into a plain cream base. The E. coli JM101(pWKW2) excretion system [1, 2] was employed to express extracellular rhEGF, which was then purified to homogeneity according to a previously described protocol [3].

Discussion

We retrospectively analyzed all the SJS cases in our department over the past two years and the details are summarized in Table 1. We noticed that SJS cases in our series are drug-induced, similar to published data [5]. Drugs most frequently implicated in SJS induction include sulfonamides (sulfadoxine, sulfasalazine, cotrimazole), allopurinol, carbamazepine, phenylbutazone, piroxicam, aminopencillins, cephalosporins, fluoroquinolones, vancomycin, rifampicin, ethambutol, diclofenac, ibuprofen, naproxen and thiabendazole. The pathogenesis of SJS is unknown, but is consistent with an immunological mechanism, i.e., a cell-mediated cytotoxic reaction against epidermal cells. The drug metabolites may act as haptens binding to the keratinocytes in the skin and making them immunogenic [6]. The epidermis becomes infiltrated by activated lymphocytes, mainly CD8 cells and macrophages. Cytokines produced by activated mononuclear cells and keratinocytes probably contribute to local cell death, fever and malaise. The time from drug exposure to the onset of symptoms is usually a few days. Patients may experience fever and influenza-like symptoms 1-3 days prior to onset of the mucocutaneous lesions, involvement in the conjunctival, scrotal, oral cavity and perianal areas. The patient described here also demonstrated dysphagia, photophobia, painful micturition and defecation, and anxiety. Early diagnosis and withdrawal of suspected drugs are of utmost importance in the management of SJS. Replacement of IV fluids and electrolytes should be used similar to treating patients with third-degree thermal burns. In our series, all patients received systemic steroid. However, there is controversy concerning the routine use of systemic corticosteroids in the management of SJS. Some claim beneficial effects, particularly if corticosteroids are given in high doses early, while others discourage its use [6, 7].

High doses of IV immunoglobulins and pentoxiphyllin IV by continuous drip, early in the eruption, have been anecdotally reported to be beneficial. The eruption usually starts improving on day 4-5 with conventional treatment. Epithelization begins within a few days and is completed in a few weeks. Most of our patients required more than 14 days to have their eruption totally subside. The response demonstrated by this man is remarkable in comparison to our historical cases. His wounds healed much more quickly, he felt less pain, and he was discharged early from the hospital.

Both animal and human skin explant models have demonstrated an effect of EGF in stimulating epithelial regeneration from the wound edge [8, 9]. Recently, EGF has been demonstrated by our group to be useful in enhancing diabetic foot wound healing [10].

In summary, the optimal management of SJS should include immediate removal of the offending agent, early attention to fluid and electrolyte status, and the prevention of infection. Use of corticosteroid remains controversial. In addition, we have demonstrated the successful application of EGF in reducing pain and promoting wound healing in this case of drug-induced SJS.

Acknowledgements: We thank Dr. Jim Hackett for reading the manuscript and Bio-Click Technologies Ltd., Hong Kong, for the generous provision of rhEGF.

References

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