Phenylketonuria

I report a patient with phenylketonuria who presented with pemphigus foliaceus or tinea amiantacea. The rash resolved with treatment with tetracycline and niacinamide. This article outlines the uses and mechanisms of this therapy with particular attention to its use in pemphigus, treatments, and scalp findings of pemphigus foliaceus and the dermatological manifestations of PKU.

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Case Report

A 38 year old white female presented with a six-month history of body and scalp rash. She had phenylketonuria (PKU) which had not been recognized in the neonatal period and her diet had not been modified, resulting in mental handicap. Physical examination revealed crusted red erosions with scale on her body (Figures 1, 2, 3) and pityriasis amiantacea (Figure 4) in her scalp. Potassium hydroxide preparations of her body and scalp did not reveal hypae. A biopsy of a body erosion showed acantholysis and intraepidermal clefting with an infiltrate of eosinophils suggesting a diagnosis of pemphigus. A subsequent biopsy for direct imnunofluorescence highlighted desmoglein (1) antibodies confirming a diagnosis of pemphigus foliaceus.

[FIGURE 1-4 OMITTED]

She was treated with tetracycline 500 mg three times a day and niacinamide 500 mg four times a day due to logistical complications of other therapies. In addition, fluocinolone acetonide oil (Dermasmoothe FS) was applied to her scalp at night under a shower cap and washed out in the morning with fluocinolone acetonide solution 0.01%.

The scalp rash resolved over several months and her treatment was discontinued. Her body rash resolved over the course of several months and her tetracycline and niacinamide were tapered by 500 mg each over a six-month period with no recurrence of her skin rash.

Discussion

The patient's scalp rash, PKU, and therapeutic course make this case notable. No report has noted coincident PKU and pemphigus foliaceus or tinea amiantacea. Tetracycline and niacinamide is rarely used in this condition. This article outlines the uses and mechanisms of this therapy with particular attention to its use in pemphigus, treatments, and scalp findings of pemphigus foliaceus and the dermatological manifestations of PKU.

Tetracyclines and niacinamide are used to treat various skin conditions1. Nicotinamide inhibits polymorphonuclear cell and eosinophil chemotaxis and blocks IgE-mediated histamine release and mast cell degranulation leukocyte protease release. Both agents inhibit lymphocyte blast transformation in vitroz.

For bullous pemphigoid, tetracycline and niacinamide is widely used, similar in effect to prednisone and mostly side effect free (3). They have been used to treat cicatricial pemphigoid (4), linear IgA dermatosis (5), ocular cicatricial pemphigoid (6), erythema elevatum diutinum (7), dermatitis herpetiformis (8) (sometimes with heparin (9)), and lichen planus pemphigoides (10).

Minocycline is also used. Minocycline and nicotinamide have treated pemphigoid gestationis (11), pemphigus vegetans with esophageal involvement (12), bullous pemphigoid (13), and oral pemphigus vulgaris (14). Minocycline can induce side effects. Severe drug-induced pneumonitis occurred with minocycline and nicotinamide therapy of a bullous pemphigoid (15).

Various treatments exist for pemphigus foliaceus. Mild pemphigus vulgaris and pemphigus foliaceus can be treated with topical corticosteroids (16). Oral corticosteroids, dapsone, cyclophosphamide, and azathioprine are often used. Severe cases can be treated with extracorporeal photochemotherapy (17), mycophenolate mofetil (18), and intravenous immunoglobulins (19). Hydroxychloroquine is another option (20) especially in children with photodistributed lesions (21).

Tetracycline alone (22) or with niacinamide can treat pemphigus. They have effectively treated pemphigus foliaceus alone (23) and associated with bullous impetigo (24). They might help long-term treatment of pemphigus vulgaris (23). One study has questioned its effectiveness as monotherapy for pemphigus variants (26). This combination is not the standard therapy for pemphigus, as it is for bullous pemphigoid.

Pemphigus variants commonly involve the scalp (27). Childhood pemphigus foliaceus typically causes scalp erythema and scaling; sometimes, blisters and oozing are present, commonly misdiagnosed as impetigo or seborrheic dermatitis (28). While this patient's scalp was not biopsied, the crusts on erythematous plaques were consistent with pemphigus foliaceus. After resolution of the body and the completion of oral treatment concluded the scalp rash did not recur. Even if her tinea amiantacea was a manifestation of seborrheic dermatitis, it would be of note because it occurred with PKU and pemphigus foliaceus of the body.

Classical PKU is caused by a deficiency of phenylalanine hydroxylase, resulting in increased levels of phenylalanine and derangements in aromatic amino acid metabolism. PKU has been linked to seborrheic dermatitis (29). This link might relate to the increased sebum excretion rate in female PKU patients, an increase that may be related to a depletion of midbrain dopamine and release of the sebotrophic hormone (30). It might also relate to and its concomitant problems in biotin metabolism. PKU is also linked to pseudoscleroderma (31), hypopigmentation (32), reticulosarcoma-like skin lesions (33), dysgammaglobulinemia (34), and iatrogenic skin lesions (35). Macular anetoderma, secondary to lichen sclerosus et atrophicus, acanthosis nigricans with apocrine hydrocystoma (36), and infantile acrodermatitis enteropathica (37) have occurred with PKU.

This case underlines an interesting (if chance) association of skin diseases and the need to be flexible in dermatological therapy. Due to their mild side effects, tetracycline and niacinamide merit a trial in patients with mild pemphigus foliaceus in whom topical medications and strong oral medications are difficult to deploy.

References

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NOAH SCHEINFELD MD DEPARTMENT OF DERMATOLOGY, ST. LUKE'S ROOSEVELT HOSPITAL CENTER NEW YORK, NY

ADDRESS FOR CORRESPONDENCE:

Noah Scheinfeld, MD

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