Buschke-Fischer-Brauer Keratoderma: Linear Variety Associated with Hodgkin's Lymphoma.

Palmo-plantar keratodermas (PPKD) are a diverse group of acquired and hereditary disorders, characterized by excessive thickening of the skin of palms and soles. Here, we report a case of Type I or Buschke-Fischer-Brauer variant of punctate palmo-plantar keratoderma, in a 66-year-old gentleman. The association of our case with Hodgkin's lymphoma along with linear configuration of lesions on the palms evoked the current report.

What was known?

Buschke-Fischer-Brauer keratoderma is a variant of punctate palmo-plantar keratoderma

It is known to occur in association with certain malignancies.

Introduction

The Palmo-plantar keratodermas (PPKDs) are a heterogeneous group of disorders chiefly characterized by the deposition of excessive keratin in the horny layers of palms and soles. They can be either hereditary or acquired or exist as a part of a plethora of skin disorders like psoriasis, hyperkeratotic eczema etc., Clinically, the PPKDs are of four types: Diffuse, focal, punctuate and striate.[1] Hereditary punctate palmo-plantar keratoderma (PPKD) is a rare autosomal dominant disorder, with variable penetrance. Type 1 hereditary punctate PPK is an uncommon variant of this genodermatosis. In 1910, Brauer and Fischer described it as “keratoderma maculosa disseminata palmaris et plantaris.” Brauer demonstrated its hereditary nature with a similar presentation, two 2 years later, in 1912.[2] Later, this condition came to be known as Brauer-Buschke-Fischer keratoderma.

Case Report

A 66-year-old, non-smoker, non-alcoholic gentleman, who was an agriculturist by profession was admitted with complaints of night sweats, unexplained weight loss of >10% over the preceding 2 months and anorexia. He was found to have cervical lymphadenopathy and hepatosplenomegaly. After routine investigations, urine and stool examination, X-ray chest, knee, lumbar spine and USG whole abdomen; he was diagnosed with Stage II Hodgkin Lymphoma as per Ann Arbor classification system. He was referred to us with multiple hyperkeratotic plaques and papules on both palms and soles. On enquiry, he revealed that these lesions have been present since 17 years of age. Initially, they started as small, hard papules on the lateral aspect of his palms, which coalesced at certain areas to give a warty appearance. Gradually, over the course of years, the lesions increased in number and size, and involved both palms and soles. The lesions were mostly asymptomatic in nature; however, there was complaint of pain at the pressure points. The patient denied any history of itching, bleeding or any change associated with climatic change. He occasionally tried to remove the hard papules, but they spontaneously reformed within a fortnight. There was no history of hyperhidrosis, visual or oral problems, or joint pain. There was no evidence of any exposure to arsenic, and no other person in his locality presented with similar complaints. However, he revealed that similar skin lesions were present in five of his family members who lived at separate places–father, brother, nephew and two of his sons thus hinting towards a possible autosomal dominant mode of inheritance, involving three generations. Strikingly, the male members have been affected, sparing the females [Pedigree chart 1].

Chart 1

Pedigree chart showing the occurrence of the disease among the family members

On cutaneous examination, both his palms and soles were studded with small, 1-3 mm, discrete yellow-brown pearly hyperkeratotic papules with a central depression (crateriform). At certain places, these papules had coalesced to form bizarre shaped, verrucous plaques about 1-2 cm in diameter. Tenderness was elicited at the pressure points. Another interesting finding in our case was the linear configuration of the lesions over the palms [Figures 1 and 2]. Hairs, nails, mucosae and teeth were absolutely normal. Examination of other systems was within normal limits. A Skin biopsy from the hyperkeratotic lesion revealed massive orthokeratotic hyperkeratosis, hypergranulosis and acanthosis. However, cornoid lamellae were absent [Figures 3 and 4]. Besides, there wasn’t any feature suggestive of acrokeratoelastoidosis. The dermis was slightly compressed below the epidermis level by the keratotic plugs and relatively free of inflammatory infiltrate. The histopathological findings were consistent with Type I hereditary punctate palmo-plantar keratoderma (PPKD) (Buschke-Fischer-Brauer keratoderma) associated with Hodgkin's lymphoma. The patient was prescribed treatment with 5% salicylic acid and 20% urea, apart from regular emollients to soften the lesions. The patient has been suggested to follow up at regular intervals.

Figure 1

Clinical photograph showing punctate palmoplantar keratoderma of the palms. Note the linear configuration of the lesions

Figure 2

Clinical photograph showing punctate palmoplantar keratoderma of the soles

Figure 3

Photomicrograph showing massive orthokeratotic hyperkeratosis. Note the absence of coronoid lamellae (H and E, ×10)

Figure 4

Photomicrograph showing hypergranulosis and acanthosis (H and E, ×40)

Discussion

Punctate keratoderma also called keratoma dissipatum; keratoderma punctate; papulosa; disseminated clavus (Davies-Colley 1879) is one of the clinical variants of PPKD. Acquired forms of punctate PPKD may be associated with Lynch type II malignancies,[1] chronic arsenicosis, angiosarcoma of liver, bronchial adenocarcinoma.[3] Afro- Caribbeans with atopic diathesis, sometimes exhibit a distinct variety–acquired punctate keratoderma of the palmar creases.[4]

The hereditary varieties of punctate keratoderma can be classified into 3 types:[3]

Type 1 (Brauer-Buschke-Fischer keratoderma): Autosomal dominant condition with onset in the later half of second decade, punctate, keratotic papules and plaques in an irregular distribution, possible association with malignant conditions

Type 2 (porokeratosis punctata palmaris et plantaris): Numerous, tiny, pruritic keratotic spines resembling the spines of a music box. On histology, columnar parakeratosis is seen simulating cornoid lamella

Type 3 (acrokeratoelastoidosis lichenoides): Polygonal or crateriform discrete papules on the lateral aspect of palms and soles.

Recently, a unilateral linear variety of punctate PPK has been described.[5] In our case as well, the linearity of the lesions could be well appreciated on the palms. Features that support the diagnosis of Type I hereditary punctate PPK in our patient include a family history suggestive of a possible autosomal dominant mode of inheritance spanning over three generations, clinical findings of multiple hyperkeratotic, crateriform papules and plaques involving the palms and soles, and absence of cornoid lamella on histopathological examination.

The mode of inheritance is autosomal dominant. Steffen Emmert et al., have studied 47 patients in 14 families with Brauer-Buschke-Fischer keratoderma and calculated a frequency of 45.4% affected children from known-affected individuals.[6] Recent advances have shown defects in keratins, loricin, desmosomes, connexins and cathepsins.[7]

Brauer-Buschke-Fischer PPKD may be associated with Lynch type II malignancies,[1] liver, bronchus, squamous cell carcinoma of chest wall, ethmoidal carcinoma.[3] Hodgkin's lymphoma, malignancies of the colon, pancreas, kidney, breast,[8] prostatic carcinoma and atypical fibroxanthoma,[9] Various studies which have corroborated the association of this PPKD with different types of malignancies has have been tabulated [Table 1]. The malignancies are not a chance occurrence and can be explained as both the keratoderma and malignancies may be caused by a defect in a gene which has a role in epithelial development and regulation of keratin expression.

Table 1

Association of Buschke-Brauer-Fischer PPKD with different malignancies at a glance

Calluses (occur mainly over the pressure points) and viral warts could be excluded clinically and histologically (no parakeratosis or cell vacuolization). The other important differential considered was arsenical keratosis, however it was ruled out by history (absence of similar skin lesions in the locality which share a common water source) as well as examination of hair, nails and drinking water sample. Thus, the characteristic morphological and histological findings, along with a positive family history and the absence of similar skin lesions in the neighborhood, reaffirmed the diagnosis of Brauer-Buschke-Fischer variety of hereditary punctate PPKD in our case. The association of this entity with Hodgkin's lymphoma in our case, has made it even more unique.

What is new?

Linear configuration of palmar lesions in a case of Brauer-Buschke-Fischer variety of hereditary punctate palmoplantar keratoderma is an extremely rare incidence

To the best of our knowledge, association of Brauer-Buschke-Fischer keratoderma with Hodgkin's lymphoma is not yet reported from India.