Increased risk of squamous cell carcinoma in junctional epidermolysis bullosa.

Non-Herlitz junctional epidermolysis bullosa (JEB) is an autosomal recessive genodermatosis characterized by skin fragility and blistering. It is usually caused by mutations in the genes encoding the basement membrane proteins laminin 5 or type XVII collagen. Clinically, impaired wound healing and chronic erosions cause major morbidity in affected patients. Previously it was thought that these individuals, unlike patients with dystrophic EB, did not have an increased risk of developing skin cancer. However, we describe three patients with non-Herlitz JEB (aged 42, 56 and 75 years) who developed cutaneous squamous cell carcinomas (SCCs). The tumours were well-differentiated in two cases, but one patient had multiple primary SCCs that were either well- or moderately differentiated. Most cases of SCC in non-Herlitz JEB described have occurred in those with laminin 5 defects and on the lower limbs. These clinicopathological observations have important implications for the management of patients with this mechanobullous disorder as well as providing further insight into the biology of skin cancer associated with chronic inflammation and scarring.

Groin dissections in epidermolysis bullosa: a report of groin dissection for the control of metastatic squamous carcinoma in patients with epidermolysis bullosa.

Epidermolysis bullosa predisposes to the development of squamous cell carcinoma. Despite regular surveillance, the majority of severely affected epidermolysis bullosa patients die from metastatic spread. There are no reports on regional control of metastatic spread. We describe our experience with two cases of groin dissection in epidermolysis bullosa. By anticipating the pitfalls in the perioperative care of patients with epidermolysis bullosa, we feel confident that they should make a full recovery.

Recurrent molecular abnormalities in type VII collagen in Southern Italian patients with recessive dystrophic epidermolysis bullosa.

In this study we searched for mutations in the type VII collagen gene (COL7A1) in 10 families from Southern Italy with severe generalised recessive dystrophic epidermolysis bullosa using PCR amplification of genomic DNA, heteroduplex analysis and direct nucleotide sequencing. Our principal aim was to identify any recurrent mutations in COL7A1 that might facilitate future mutation detection strategies in this population. Three recurrent COL7A1 mutations were delineated in six of the 10 families: a frameshift mutation in exon 4, 497insA, was detected in three affected individuals from three families, a deletion mutation at the acceptor splice site of intron 114/exon 115, 8441-14del21, was found in five patients in three of the families, and an intron 49 acceptor splice site mutation, 4783-1 G-to-A, was identified in three subjects in two families (GenBank accession no, L02870). Haplotype analyses showed evidence for propagation of common ancestral mutant COL7A1 alleles for each of these recurrent mutations. These results contribute significantly to understanding the nature of COL7A1 pathology in patients from Southern Italy and in designing future approaches to mutation detection.

The 'Pinocchio' nasal deformity due to cavernous lymphangioma.

The 'Pinocchio' or 'Cyrano' nose is a rare condition in which deformity of the nasal tip is produced by an underlying soft tissue tumour. Previously reported cases have been due to either capillary or cavernous haemangiomas (angiolipomas). The deformity is the cause of much teasing in children. There has been debate as to whether surgical intervention is indicated, as a proportion of cases will regress spontaneously. We report a case of 'Pinocchio' nose with a lymphangioma of the nasal tip which is previously undescribed and review the options for management.

The clinical spectrum of lipoatrophic panniculitis encompasses connective tissue panniculitis.

Two patients with widespread, chronic, relapsing panniculitis resulting in disfiguring lipoatrophy are reported. Histology in both cases showed a mixed septal and lobular panniculitis, with lipophagia. The clinical appearance and histology suggested a diagnosis of lipoatrophic panniculitis. Both cases had features of connective tissue panniculitis, which is likely to be a subtype of this condition. Treatment of lipoatrophic panniculitis can be difficult. Our first patient initially responded well to antimalarial therapy, allowing plastic surgical repair of the defects to be carried out.

The anaesthetic management of patients with dystrophic epidermolysis bullosa. A review of 44 patients over a 10 year period.

The case notes and anaesthetic charts of 44 patients with dystrophic epidermolysis bullosa were reviewed retrospectively. A total of 390 general anaesthetics were performed for 469 surgical procedures over a 10-year period. Procedures included repair of syndactyly, dilatation of oesophageal strictures, extraction of teeth, excision of skin tumours and other procedures related to dystrophic epidermolysis bullosa. Anaemia, thrombocytosis and hypoalbuminaemia was found in many patients pre-operatively. Damage to skin or mucosa occurred peri-operatively. Four patients developed bullae around the head and neck, two patients developed oral or pharyngeal bullae and three patients developed conjunctival abrasions including one with a new corneal ulcer. There were no reports of laryngeal bullae and no bullae associated with intramuscular injections or the use of limb tourniquets. Thirty-one patients (70%) had evidence of oesophageal strictures and six regurgitated peri-operatively. In all cases there was a history of oesophageal disease. In 10 patients (23%) intubation of the trachea was difficult. It was carried out by various methods including blind nasal and fibreoptic intubation or by using the laryngeal mask airway. One patient requiring a series of general anaesthetics had a tracheostomy formed after fibreoptic intubation. Previous reports have suggested problems with the use of suxamethonium, nondepolarising muscle relaxants and thiopentone. These agents were all used in many of our patients without any adverse effects. There was one intra-operative death in a 35-year-old woman having an oesophageal dilatation which was complicated by oesophageal rupture.

Cultured keratinocyte allografts and wound healing in severe recessive dystrophic epidermolysis bullosa.

BACKGROUND: Patients with recessive dystrophic epidermolysis bullosa (RDEB) frequently have painful erosions that are slow to heal. There is no definitive treatment; therefore any therapy that improves wound healing would be beneficial to these patients. OBJECTIVE: Our purpose was to assess the effects of cultured allogeneic keratinocytes on wound healing in RDEB. METHODS: Ten patients with RDEB and dermatome-induced superficial dermal wounds were studied. Cultured keratinocyte grafts were applied to part of the wound, with another part left ungrafted. Both sites were assessed clinically and microscopically, particularly with regard to basement membrane zone reconstitution. RESULTS: Apart from minor differences in keratinocyte differentiation and a moderate analgesic effect induced by the graft, there were no other distinguishing findings in wound healing in the grafted and nongrafted sites. CONCLUSION: There was little clinical benefit from cultured keratinocyte allografts in wound healing in RDEB. However, this study showed that RDEB keratinocytes have an inherent capacity to express some type VII collagen epitopes transiently during wound healing, although this was not associated with the detection of anchoring fibrils.

Mitten deformity in severe generalized recessive dystrophic epidermolysis bullosa: histological, immunofluorescence, and ultrastructural study.

Light and electron microscopy and indirect immunofluorescence techniques were used to study the nature of the mitten deformity in five adult patients with severe generalized recessive dystrophic epidermolysis bullosa undergoing release of hand and finger contractures. Although the mitten appeared largely to be clinically separated from the underlying fixed digits, histology showed mostly normal keratinocytes beneath a thickened stratum corneum. The lower margin of the mitten was formed just below the lamina densa of the basement membrane, at a level similar to that of the usual blister formation in this condition. No anchoring fibrils and only a few distinct dermal structures were noted. A substantial portion of the mitten, however, consisted of necrotic keratinocytes without an intact basement membrane. This finding suggests that the mitten is not suitable for use as an epidermal autograft and confirms the rationale for taking split thickness skin grafts to close skin defects in patients with recessive dystrophic epidermolysis bullosa undergoing plastic surgery.

Tissue expanded free flaps.

Over the last few years there have been various reports of the use of tissue expanders as an adjunct to microvascular free transfer of tissue. This study looks at the effect of expanding the actual flap prior to transfer. Two case reports are given and it is proposed that expanded free flaps are large and thin. They have a capsule which enables them to be safely sutured under tension. They are "delayed" by the expansion process and the donor deformity is minimal. It is suggested that tissue expansion is a useful technique prior to free flap transfer for the reconstruction of large defects.

The surgical management of dystrophic epidermolysis bullosa (excluding the hand).

Fifty patients with Dystrophic Epidermolysis Bullosa (DEB) underwent surgery including release of limb, oral, anal, eye and penile contractures and treatment of chronic skin ulceration or skin tumours. Correction of contractures involves extensive release of skin and underlying tissues, with split skin grafting of secondary defects. Specific regions are discussed. Recurrence is inevitable due to ongoing disease; however, functional improvement is obtained for several years. Management of chronic skin ulceration with split skin grafting has failed to produce long term healing, with local flaps successful but limited by the problem of donor site instability. Nine of the 17 patients over 20 years of age developed squamous cell carcinomas (29 lesions), benign hyperkeratosis (9) or malignant melanoma (1) requiring excision and skin grafting or amputation of digits. Local recurrence was infrequent (3 squamous cell carcinomas), with distant metastatic spread occurring in 1 patient.

Experience in the surgical management of the hand in dystrophic epidermolysis bullosa.

Between 1981 and 1990, 45 patients (80 hands) underwent 122 hand operations, involving extensive release of contractures and pseudosyndactyly, with split skin grafting of secondary defects. Other procedures included the use of Kirschner wires, tendon release and arthroplasty. A postoperative programme of long term night splintage was employed. Finger extension was significantly improved for up to 5 years postoperatively, with a mean extension deficit preoperatively of 139 degrees, at 1 year postoperatively 60 degrees (p < 0.0001) and 4 years 84 degrees (p < 0.05). Preoperatively, pseudosyndactyly was present in 64.3% of web spaces, in comparison to 13.3% at 1 year, 37% at 4 years (p < 0.01) and 66.6% at 5 years (N.S.) postoperatively. Adduction contracture of the thumb was significantly improved for 2 years postoperatively. Functional assessment of 18 hands showed significant improvement postoperatively.

Epidermolysis bullosa complicated by squamous cell carcinoma: report of 10 cases.

Epidermolysis bullosa (EB) refers to a group of hereditary mechano-bullous conditions, many of which are associated with chronic scarring. Several forms of the disease have been reported in association with cutaneous malignancy. We present a series of 10 EB patients (eight generalised recessive dystrophic EB, one dominant dystrophic EB, one non-lethal junctional EB) aged 24-55 years with a total of 29 squamous cell carcinomas (SCC). Three patients died from metastatic disease associated with invasive, poorly differentiated SCC. Six cases had multiple primary SCC, including three patients with simultaneous multifocal disease. Twenty-eight of the 29 SCC arose on the limbs. Histology revealed that most of the SCC were well or moderately differentiated (22/29). Unusual histological findings included two verrucous SCC, as well as a spindle cell (angiosarcoma-like) SCC. Most of the SCC developed in areas of chronic non-healing ulceration (10/29) or longstanding hyperkeratotic crusting (14/29). The dermis around or beneath the carcinomas was densely scarred, more so than in non-malignant areas. In some cases it was difficult to distinguish the clinical appearances of certain areas of chronic ulceration, scarring, and crusting typical of dystrophic EB from many of the SCC. This study underlines the need for constant vigilance for the development of carcinomas in this group of patients, the occasional diagnostic difficulty, and the potential for metastasis.

Pain and forehead expansion.

Tissue expansion of the forehead by intermittent bolus injection in three patients was noted to be extremely painful. This stimulated a prospective study in four patients whose discomfort was found to be related to a sharp rise in intraluminal pressure after bolus inflation. Tolerable infusion volumes were small (mean 6.25 cc) and associated with high pain scores (mean 7/10). Adequate expansion was protracted (mean 45 1/2 days) and was limited by pain. To eliminate the sharp rises in pressure associated with expansion by bolus injection, a syringe pump was used in two further inpatients. Adequate expansion was both quicker (mean 8.5 days) and less painful (mean pain score 2.6/10).

Metastatic squamous cell carcinoma resembling angiosarcoma complicating dystrophic epidermolysis bullosa.

We report a patient with generalized recessive dystrophic epidermolysis bullosa (RDEB) who developed 3 squamous cell carcinomas. The tumours appeared simultaneously at acral sites on both upper limbs and were poorly differentiated. Despite surgery and radiotherapy the patient died from metastatic disease within 6 months of presentation. This case highlights many of the typical features of this complication of RDEB, including the overall poor prognosis. Of particular interest was the histology of one of the tumours which caused diagnostic difficulties: haematoxylin and eosin staining suggested an angiosarcomatous pathology, but the use of immunocytochemistry proved that the tumour was a squamous cell carcinoma in origin.

The eye in dystrophic epidermolysis bullosa: clinical and immunopathological findings.

The ocular findings in a series of patients with dystrophic epidermolysis bullosa are presented. An immunopathological technique using monoclonal antibodies for examining components of the epithelial basement membrane of the conjunctiva is described and the results obtained on a conjunctival biopsy from a patient with dystrophic epidermolysis bullosa are presented.

Congenital divided naevus of the eyelids.

A newborn infant presenting with a divided congenital melanocytic naevus of the eyelid is described. Because of the severe disfigurement, risk of later malignant change in the lesion, and the possibility of deprivation amblyopia, early surgical treatment is recommended for all medium and large congenital melanocytic naevi of the eyelid. Surgery in the first few months of life gives the best cosmetic results.

The role of anaesthetic management in enhancing peripheral blood flow in patients undergoing free flap transfer.

An anaesthetic protocol is described that is designed to promote peripheral blood flow and prevent vascular spasm in patients undergoing free flap transfer. The technique has been used successfully over a period of 3 years at St Thomas' Hospital, London, and since its introduction vascular spasm has ceased to be a major intraoperative problem.