Mal de meleda with lip involvement: a report of two cases.

Mal de Meleda is a rare autosomal recessive transgradient palmoplantar keratoderma characterized by transgradient keratoderma with associated scleroatrophy, nail changes, pseudoainhum around digits and perioral erythema, without a tendency for spontaneous resolution. Involvement of the lip by keratoderma has not been reported in the English literature. Here we present two cases of Mal de Meleda with unusual lip involvement. The first case was a 15-year-old girl, born of second-degree consanguineous marriage, who presented with transgradient palmoplantar keratoderma from 6 months of age, with lichenoid papules and plaques on the elbows and knees, conical tapering of the distal digits, flexion deformity of several fingers, digital constriction, knuckle pads and lip involvement. The second case was a 24-year-old male with transgradient palmoplantar keratoderma since birth. He also had scaly plaques on the extensors of bilateral knees and elbows, knuckle pads, pseudosclerodermatous fingers with conical tapering, digital constrictions at various places with mild flexion deformity and lip involvement. Both patients were otherwise normal without any family history.

Introduction

Mal de Meleda (also known as keratoderma palmoplantaris transgrediens, acroerythrokeratoderma, keratosis extremitatum hereditaria progrediens)[1] is a rare autosomal recessive transgradient keratoderma named after the Croatian island of Meleda (Mljet).[2] This keratoderma begins between the time of birth and 3 years of age, and is characterized by transgradient keratoderma with sharp demarcation, erythema with associated scleroatrophy, nail changes, pseudoainhum around digits and perioral erythema without a tendency for spontaneous resolution. Although perioral erythema is well known in Mal de Meleda, involvement of the lip by keratoderma has not been reported in the English literature. Here we present two unrelated cases of Mal de Meleda who had typical features of the syndrome with unusual lip involvement.

Case Reports

Case 1

A 15-year-old girl presented with thickening of the skin on palms and soles from 6 months of age. There was progressive worsening with slow involvement of the dorsal aspects of the palms and soles with increasing age. She also had pigmented, rough, raised grouped lesions on the elbows and knees from 5 years of age. There was redness of lips since childhood, which developed into mild thickening and dryness recently. She was born of second-degree consanguineous marriage. Developmental milestones were normal and performance in school was above average. There was no history of hearing impairment, eye problem or dental caries. Two other siblings, parents and relatives, did not have similar complaints. On examination, there was diffuse palmoplantar keratoderma involving bilateral palms and soles and extending proximally up to the wrists and the dorsa of hands and feet with well-defined margins [Figures 1 and 2]. The skin on the palms and soles was thick, waxy and yellow with loss of dermatoglyphics. There were a few areas of erosions in the web spaces. There was conical tapering of the distal digits. Flexion deformity due to contractures was noted in several fingers. Mild digital constriction was seen in the little finger of the left hand. Hyperkeratotic plaques mimicking knuckle pads were seen on the proximal interphalangeal joints. Multiple well-defined lichenoid papules were present on the extensor aspects of the elbows. Well-defined plaques were seen on the extensor aspects of the knee joints [Figure 3]. Nails were thickened with longitudinal ridges and prominent lunulae. The great toenail of the left foot was dystrophic. Soles had pitted keratolysis and fissuring. Lips were erythematous, dry with mild hyperkeratosis [Figure 4]. There were a few erythematous plaques around the mouth and in both cubital fossae. Histopathology of palmar skin showed hyperkeratosis, hypergranulosis, and acanthosis. There was no feature of epidermolytic hyperkeratosis. A diagnosis of Mal de Meleda was made based on the above-mentioned features.

Figure 1

Transgradient palmoplantar keratoderma with sharp margins, conical tapering of the fingers, flexion deformity, and digital constriction of the little finger of the left hand

Figure 2

Transgradient palmoplantar keratoderma with sharp margins, conical tapering of the fingers, flexion deformity, and digital constriction of the little finger of the left hand

Figure 3

Scaly plaques on the extensor aspect of the left knee

Figure 4

Lip involvement with perioral lesions

Case 2

A 24-year-old male presented to our dermatology OPD with thickening of skin of palms and soles since birth and with progressive involvement of the dorsa of hands and feet for last 5 years. There was history of repeated blistering and painful fissuring of palms. He also had hyperpigmented, raised, scaly plaques on the extensors of bilateral knees and elbows for last 6 months. He also had redness of lower lip with mildly painful fissuring of bilateral angles of mouth of 6 months duration. He was otherwise normal without any systemic abnormalities. No family member was affected by similar illness. On examination, there was diffuse transgradient palmoplantar keratoderma involving bilateral palms and soles extending up to the dorsa of hands and feet with ill-defined irregular margins and prominent knuckle pads [Figure 5]. Skin on the palms and soles was thick, waxy, yellowish, malodorous, with loss of dermatoglyphics. There were multiple erosions and fissuring of varying sizes on both the palms, and pitted keratolysis on the soles. Fingers had pseudosclerodermatous appearance with few showing conical tapering and digital constrictions at various places with mild flexion deformity. Nails showed thickening and hypercurvature with dystrophic changes of bilateral great toenails. The patient had multiple hyperkeratotic, scaly, irregular, ill-defined plaques on extensors of bilateral elbows and knees. Along with these features the patient also had a dry, erythematous, thickened lower lip with angular cheilitis [Figure 6]. Histopathology of palmar skin showed lining of stratified squamous epithelium with hyperkeratosis, hypergranulosis, and acanthosis. Superficial dermis shows mild perivascular lymphocytic infiltrates. A diagnosis of Mal de Meleda was made. For logistic reasons, genetic analysis for Slurp1 could not be done in both cases.

Figure 5

Transgradient palmoplantar keratoderma with ill-defined margins, conical tapering of the fingers, flexion deformity, and digital constriction of the little finger of the right hand

Figure 6

Involvement of the lower lip with angular cheilitis

Discussion

The obligatory clinical features of Mal de Meleda are[3] (1) autosomal recessive inheritance, (2) onset of diffuse keratoderma palmoplantaris soon after birth (or up to 3 years of life),[1] (3) transgressive and progressive nature of the keratoderma which tends to involve the dorsa of hands and fingers, feet and toes, flexor aspect of the wrist (“glove and stocking keratoderma”) with sharp margin.[1] Hyperkeratotic plaques resembling knuckle pads may be seen on the interphalangeal joints.[1] The facultative clinical features are[3] (1) palmoplantar hyperhidrosis, (2) pitting in the keratoderma palmoplantaris, (3) lichenoid polycyclic plaques on the elbows, knees, and groins, (4) subungual keratosis, koilonychia, dystrophy of the great toenail, (5) progressive conical tapering of the fingertips which may lead to contractures of the fingers, (6) perioral erythema, (7) high arched palate, (8) corneal lesions. Digital constrictions (pseudoainhum) and angular cheilitis[2] are also common. Other rare features include lingua plicata, syndactyly, left handedness and hair on palms and soles.[1] The involvement of the lips as was seen in both our cases is unique and hitherto unreported in the English literature.

There is a great interindividual variation in the clinical manifestations of Mal de Meleda which should be differentiated from other similar palmoplantar keratoderma syndromes.[3] Greither's disease has several clinical similarities with Mal de Meleda syndrome, but can be differentiated based on the following features. Greither's disease is autosomal dominant, starts during 8-10 years of age with a gradual onset and a tendency to improve with age.[2] Mal de Meleda is autosomal recessive, appears early after birth and slowly progresses without any tendency for spontaneous involution.[4] Both have transgradient keratoderma and hyperkeratotic plaques on the extensor aspects of the knees and elbows. However, perioral erythema is seen in Mal de Meleda syndrome.[3] In contrast to Mal de Meleda syndrome, the palms and soles may be spared in Greither's disease.[4] Conical tapering of the fingertips seen in Mal de Meleda syndrome is not seen in Greither's disease.[3] Constrictive bands and nail changes are frequent with Mal de Meleda, but unusual in Greither disease.[5] Mal de Meleda syndrome also has typical nail changes.

Huriez syndrome (also referred to as “sclerotylosis”) is an autosomal dominant genodermatosis, characterized by the triad of congenital diffuse scleroatrophy of the distal extremities, mild or lamellar keratoderma of the palms and to a lesser extent the soles, presence from birth and ridging or hypoplastic nail changes.[67] There is also an absence of dermatoglyphics.[2] Atrophic parchment-like skin is present on the dorsal surface of the hands. Dense hyperkeratosis gives a pseudosclerodermatous appearance with nail atrophy.[2] Nail changes include hypercurvature, longitudinal ridging, onychorrhexis, and koilonychia.[2] Another prominent feature of Huriez syndrome is almost invariable family history.[8]

Olmsted's syndrome is a severe, cicatrizing transgradient palmoplantar keratoderma with keratotic plaques around the mouth, nose and anus. Onset is in the first year of life, with symmetrical, sharply defined palmar and plantar keratoderma surrounded by erythema, flexion deformities, constriction or spontaneous amputation of the digits, onychodystrophy, follicular keratosis, congenital universal alopecia, hyperextensibility of the joints, absence of premolar teeth and keratosis of the oral mucosa.[29]

Vohwinkel's syndrome is an autosomal dominant palmoplantar keratoderma characterized by honeycomb-like keratoderma beginning early in life associated with stellate or “starfish” keratoses on the dorsa of hands and feet, and the formation of circumferential bands around digits (“pseudo-ainhum”) and sensorineural deafness.[210] Vohwinkel's syndrome was ruled out in our case by the absence of honey-comb keratoderma and sensorineural hearing loss. Camisa's syndrome is a variant of Vohwinkel's syndrome where sensorineural hearing impairment is absent, but these patients have mild ichthyosis[11] which was not seen in our case.

Papillon Lefevre syndrome (PLS) is characterized by palmoplantar hyperkeratosis, severe periodontitis and premature loss of teeth. It manifests by 1-4 years of life and patients become edentulous by early teens.[12] PLS was easily ruled out in our case by the presence of normal teeth and the absence of periodontitis.