PHARMACOLOGY AND THERAPEUTICS

RECESSIVE DYSTROPHIC EPIDERMOLYSIS BULLOSA TREATED WITH PHENYTOIN ABDULAZiZ A. ABAHUSSEIN, M,D,, AHMAD A, AL-ZAYIR, M.D,, MPEDAD Z. MOSTAFA, M.D., AND A N E Z I N . O K O R O , M.B,, F.R.C.P, (EDIN)

Abstract Three patients with severe recessive dystrophic epidermolysis bullosa were treated with oral phenytoin and palliative and supportive measures for variable periods. Their progress was compared with that of three milder cases managed only with palliative and supportive measures. The phenytointreated group showed marked decrease in blister count, increase in trauma tolerance, a rise in hemoglobin level, and considerable weight gain. The results support earlier reports that collagenase inhibitors are useful in controlling blister formation in recessive dystrophic epidermolysis bullosa, IntJ Dermatol 1992; 31:730-732 Recent trials of oral phenytoin for the control of blister formation in recessive dystrophic epidermolysis bullosa (RDEB)^"^ encouraged us to conduct an evaluation of oral phenytoin in three of our patients who had a confirmed diagnosis of severe RDEB. We report our findings in these patients and in three milder cases of RDEB managed with only palliative and supportive measures. Materials and Methods From our studies on 16 cases of epidermolysis bullosa (EB), we selected three patients whose diagnosis of recessive dystrophic epidermolysis bullosa (RDEB) was based on family history and the presence of consanguinity, clinical pictures consistent with RDEB (Fig, 1), and histologic studies (Fig, 2), We treated them with oral phenytoin and palliative and supportive measures. Three milder cases of RDEB given only palliative and supportive measures were also followed-up. The initial count and long axes of blisters and erosions wete made for each patient on phenytoin, and repeated on subsequent follow-up visits. The initial trauma tolerance was determined by rubbing an area of intact skin with sterile gauze for 30 seconds to raise a blister. The trauma tolerance was reassessed on subsequent follow-up visits. The initial dose of phenytoin was 5 mg/kg/day orally in two divided doses. The dose was increased monthly until a

From the Department of Dermatology, College of Medicine and Medical Sciences, King Faisal University, Dammam, Saudi Arabia. Address for correspondence: Abdulaziz A, Abahussein, M.D,, Department of Dermatology, King Fahd Hospital of the University, P.O, Box 2208, Al-Khobar 31952, Saudi Arabia.

Figure 1.

Two-month-old infant boy with RDEB.

satisfactory clinical response was obtained. Serum phenytoin levels were measured every 2 weeks. Laboratory investigations carried out regularly were erythrocyte sedimentation rate (ESR), complete blood count (CBC), liver function tests (LFTS), blood urea, creatinine, urinalysis, stool for occult blood and microscopy, and culture and antibiotic sensitivity tests on swabs taken from erosions and ulcers.

RESULTS

The clinical features in six patients with recessive dystrophic epidermolysis bullosa, three of whom were selected for the drug evaluation, are shown in Table 1. All six patients had skin and mucosal blisters, erosions, and ulcers. All, except the patient who died in infancy, developed scars and milia. All had varying degrees of nail dystrophy. Two patients had patchy alopecia from ulceration of blisters on the scalp. Three had dysplastic

Recessive Dystrophic Epidermolysis Bullosa Abahussein et al.

Figure 2. Subepidermal bulla in RDEU. teeth, two had normal teeth, and one died before dentition appeared. The three patients selected for treatment with phenytoin had signs of internal bleeding, iron deficiency anemia, and recurrent respiratory infections. Two weeks after the start of oral phenytoin, all three patients showed significant reduction in blister count, average 53% (Table 2). The two patients who were followed up for over 1 year showed further reduction in

Figure 3.

Seven-year-old boy with RDEB.

blister count, and increased trauma tolerance. The blister count was increased in two of the untreated cases. In all three patients treated with phenytoin, there was a steady increase in hemoglobin level, and a less impressive increase in the untreated group (Table 3). A steady weight gain was recorded in all treated cases including the female infant, who later died.

Table 1. Clinical Features of Six Patients with RDEB Case No.

Sex

1

M

2

F

3

M

4

M'

5 6

M M

Age of Onset

Skin

Lesions Mucosa

Nails Some All All All Some Some

2 days 3 days 7 days 1 month 2 days 2 days

Involve,ne,tt Hair Teeth Alop

Some

— Alop

All All

Scars and Milia

Phe,iytoin Trial Yes Yes Yes No No No

Alop, scarring alopecia.

Table 2. Changes in Blister Count in Treated and Untreated RDEB Case No.

1 2 3 4 5 6

Sex M

F M M M M

Age at Diag,!osis

btitial

2 weeks

2 months 3 days 25 years 1 month 2 days 2 days

40 18 33 31 17 36

19 7 18 — — —

*Died in infancy.

731

Blister Count Fall (%) 52.5 61,1 45.5 — — —

>1 year

Fall (%)

15

62.5 *

14 42 23 27

57.5 Increase Increase 25

Phe,iytoin Yes Yes Yes No No No

International Journal of Dermatology Vol, 31, No, 10, October 1992

Table 3. Hemoglobin Levels in Treated and Untreated Cases Hemoglobin Level (g/dL)

Weight gain in the untreated group was less impressive (Table 4). No undesirable side effects were reported by patients or detected clinically or by laboratory investigations. Our prize patient was a 2-month-old male infant (Fig. 1), now aged 7 years (Fig. 3), who is a picture of good health, and is proud to demonstrate his markedly increased trauma tolerance.

Case No.

Sex

1

M F M M M M

2 3 4

5 CONCLUSIONS

6

8,5 9,5

11,5 10,2 9,2 9,3

10.8 10.5 12.3 t t t

6 months

3 year

11.8 —'-^

12,9

13.7

13,7

1

t

9,8 9.B

t

9,8

i;-

in infancy, +Not treated.

Our evaluation of phenytoin in severe cases of RDEB has confirmed the efficacy of this drug, a collagenase inhibitor"* in controlling the blistering process for a long time. The rise in hemoglobin level was a result of the elimination or control of alimentary tract bleeding. The control of buccal and esophageal mucosal erosions resulted in easier feeding and steady weight gain. In our study, it was essential to continue with the local treatment of blistered and scarred skin and mucosa, the control of recurrent infections, and the use of blended foods and vitamin and protein supplements. This study suggests that phenytoin has a definite place in the control of blister formation and its complications in recessive dystrophic epidermolysis bullosa. It should be combined with other essential modalities of treatment in order to achieve greater control of the blistering process and its complications, and to prolong useful life and minimize the disability of patients suffering from this disorder.

Table 4. Weight of Patients Following Treatment with Phenytoin Weight (kg) Case No.

Sex 1

2

3 4 5 6

Before Treatment 3 months

M F M M M M

2,0

3,4

6 mo,iths 6,3

1 year 8,7

-A-

1,4

2.0

50,3 4.3 2,6

55,2 t —t

57.5 t t

7,8

1

1'

58,5 11,9 9,2 11,8

""Died in infancy, 'Not treated.

2,

Guill MF, Junctional epidermolysis bullosa, Treatmetit with phenytoin. Am J Dis Child 1983; \37:992-995.

3,

Cooper WT, Bauer EA. Therapeutic efficacy of phenytoin in recessive dystrophic epidermolysis bullosa. A comparison of short- and long-term treatment. Arch Dermatol 1984; 120:490-495,

4,

Bauer EA, Cooper TW, Tucker DR, Esterly NB, Phenytoin therapy of recessive dystrophic epidermolysis bullosa. Clinical trial and proposed mechanism of action on collagenase, N Engl J Med 1980; 303:776-781.

DRUG NAME

phenytoin: Dilantin REFERENCES 1.

Before Phenytoin 3 months

Eisenberg M, Epidermolysis bullosa. New therapeutic approaches, Australas J Dermatol 1973; 19:1-4,

COMP. LICORICE POWDER DOSE.—Teaspoonful in a wineglass of water a t bed time.

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From the collection of "La Pharmacie Fran^aise," New Orleans, Louisiana, Mr. Ben Bavly, Curator. 732