Management of advanced foot deformities in dystrophic epidermolysis bullosa

Treatment for the characteristic hand deformities of dystrophic epidermolysis bullosa has been well described in the literature. We present our first experience delineating the surgical treatment for advanced foot deformities in this disease. This case emphasizes the need for release of contractures, the use of split-thickness skin grafts, and the need for rigid fixation to maintain surgical correction until healing is complete.     

Prenatal diagnosis of genodermatoses by ultrastructural diagnostic markers in extra-embryonic tissues: defective hemidesmosomes in amnion epithelium of fetuses affected with epidermolysis bullosa Herlitz type (an alternative prenatal diagnosis in certain cases)

Summary We report the first use of amnion epithelium for prenatal diagnosis. Prenatal diagnosis of recessive epidermolysis bullosa atrophicans generalisata gravis Herlitz type can at present be achieved with safety by detailed ultrastructural analysis of fetal skin. Because of the close developmental origin of amnion and skin, which has been elucidated by the recent development of antiamnion antibodies against dermo-epidermal junction antigens and by their abnormal binding in epidermolysis bullosa skin, there is presumably some morphological relationship between amnion epithelium and skin. In a comparative study of extra-embryonic tissues, we found ultrastructurally complete hemidesmosomes in all 24 investigated normal amnion samples from gestational weeks 15–27, but not in 7 reflected chorion samples from weeks 16–22. The results of placental chorion samples were not reliable. Amnion of 5 fetuses affected with epidermolysis bullosa atrophicans generalisata gravis revealed only hypoplastic hemidesmosomes, the same defect as in the respective skin. In a recent case where unfortunately only non-skin material was available, a positive prenatal diagnosis of epidermolysis bullosa atrophicans gravis Herlitz was performed from the amnion material. The diagnosis was confirmed by investigation of the fetal skin after termination. Investigation of amnion membranes is therefore an alternative for prenatal diagnosis of epidermolysis bullosa atrophicans gravis Herlitz in certain cases. The possibility and limitations of the general use of amnion for prenatal diagnosis are discussed.     

Calcium carbonate gel therapy for hydrofluoric acid burns of the hand

Hydrofluoric acid is used extensively as an industrial cleaning agent for metals and glass. Many workers are injured by cutaneous contact of the acid with exposed skin surfaces, particularly hands. Hydrofluoric acid burns are characterized by delayed onset of symptomatology with skin ulceration, and severe pain may be of extended duration. Treatment of hydrofluoric acid burns traditionally has consisted of local infiltration or intraarterial injections of calcium solutions. These injections are painful and frequently require retreatment. A new treatment utilizing a topical gel of calcium carbonate is described. Nine patients have been treated for hydrofluoric acid burns of the hand with calcium carbonate gel applied topically and covered with occlusive glove dressings. A gel slurry is compounded from calcium carbonate tablets and K-Y Jelly. Fingernails of the affected fingers are removed if a subungual burn is obvious. The gel is put into a surgeon's glove and placed over the burned hand. The patient replaces the glove and slurry every 4 hours for 24 hours. After the first day, the glove is discontinued unless there is resumption of painful symptoms. Full range of motion is encouraged during this interval. The calcium carbonate gel technique was successfully utilized in nine patients with no further need for injection therapy. In these patients, pain relief was obtained within 4 hours of treatment, with no further progression of skin ulceration. No reconstructive procedures were required in any patient, and only one patient did not return to full-duty work within 1 week. There were no long-term sequelae from burns treated with this topical therapy, except one patient, who presenting 24 hours after the burn, developed a digital tip neuroma that was excised.     

Genetische Ursachen für epidermale Fragilität

Genetic disorders with epidermal fragility are characterized by mechanically induced blistering of the skin and mucous membranes. The causative mechanisms are based on mutations in genes for structural proteins of the dermal-epidermal junction zone. Most of the diseases belong to the epidermolysis bullosa group and are both genetically and clinically heterogeneous. Based on the clinical phenotype alone, the diagnosis is difficult in newborns and toddlers, and sometimes in adults as well. A precise diagnosis is possible only with laboratory tests such as immunofluorescence mapping, electron microscopy, and mutation analysis. Specialized centers exist for molecular diagnostics. The treatment is symptomatic and based on the principles of good wound management and, for severe cases, multidisciplinary care. New data on the pathogenetic mechanisms of epidermolysis bullosa provide perspectives for the development of novel molecular therapies.     

Cost analysis of the Kozak protocol as used in an Ontario hospital in the treatment of children with epidermolysis bullosa.

Conventional treatment of epidermolysis bullosa is often unsuccessful. The Kozak protocol is an alternative that has been given considerable public support in Ontario. The incremental cost of this treatment program at the Hospital for Sick Children, Toronto, was examined. The departments of nursing, pharmacy and food services each kept records of salaries and supply costs applicable to the care of nine patients with epidermolysis bullosa who were treated in the fiscal year 1982-83. The selected direct costs to the hospital were compared with the projected costs if these patients had been treated in Dr. Kozak''s clinic in West Germany or under the financial arrangements offered to Dr. Kozak by the Ontario minister of health. At a total incremental cost of +255.92 per patient-day, care at the Hospital for Sick Children may not currently be the least expensive means of offering the Kozak protocol to Ontario children. However, the major expense of the program, the nurses'' salaries, could be reduced if the patients'' parents were to assume many of the nursing tasks; this would make the hospital''s program the most cost-effective method of treating children with epidermolysis bullosa.     

Combined second and third toe transfer

Historically, restoration of hand function following multiple digital amputation has been unsatisfactory. The evolution of digital reconstruction with toe transfer has enabled surgeons to reestablish prehension in these severely injured hands. A 4-year experience with 26 consecutive combined second and third toe transfers to replace missing adjacent fingers was reviewed in order to delineate the indications and technical considerations and to emphasize prevention of donor-site complications. Combined second and third toe transfer is reserved for adjacent finger amputations proximal to the digital web space with remaining fingers no longer than the small finger. Radial amputations are replaced with contralateral combined toe units, while ipsilateral toes are more ideal for ulnar amputations. Limited dorsal and plantar skin flaps extending only to the midpoint of the first and third digital web spaces allow for direct donor-site closure and uncomplicated healing. Maintenance of the plantar metatarsal arch by avoiding metatarsal shaft osteotomies or bone grafting-shortened metatarsals eliminates potential gait disturbances. When properly applied in selected patients, this single-stage microsurgical procedure can restore prehensile function, improve the appearance of the hand with multiple digital amputations, and preserve near-normal donor-foot function.     

Epidermolysis bullosa: current concepts and management of the advanced hand deformity.

A current classification of the types of epidermolysis bullosa is reviewed, in conjunction with some etiological concepts. The pathomechanics of the advanced hand deformity are discussed, and applied to a sequential plan of reconstructive surgery. The objective is the restoration of elementary hand function. Two illustrative cases are presented.     

Distal, dorsal superior extremity plasty

Multiple deep wrinkles and redundant skin over the dorsal hand, wrist, and forearm develop and become of cosmetic importance to some patients as they age. Distal, dorsal superior extremity plasty was performed in selected patients by excising redundant skin and wrinkles from the dorsal hands, wrists, and forearms. The area of skin to be excised is elliptical, with the long axis of the ellipse centered over the wrinkles on the dorsal wrist. The amount of skin to be excised (i.e., the short axis of the ellipse) is determined by grasping the dorsal wrist skin, hence advancing the dorsal forearm and hand skin, while the patient flexes the wrist. This maneuver is performed to avoid excessive excision of dorsal wrist skin, which would cause decreased wrist flexion. The surgical procedure is performed with use of magnification to avoid sensory nerve injury. A relatively large volume of lidocaine is injected subcutaneously to increase the distance between the skin and nerves and therefore decrease the risk of nerve injury. The skin edges are undermined for 1 to 1(1/2) cm, and the wound is closed in two layers. The wrist is splinted in 30 to 45 degrees of extension to decrease wound tension. The procedure produces long-lasting, good to excellent cosmetic improvement and patient satisfaction. The dorsal wrist, hand, and forearm appear smoother and more youthful, and scars are relatively inconspicuous. Potential significant complications include injury to the superficial branch of the radial nerve and dorsal branch of the ulnar nerve, wound dehiscence, and decreased range of motion of the wrist. Use of magnification, a bloodless field, injection of a relatively large volume of local anesthetic (10 to 12 cc), knowledge of regional anatomy, and careful surgical technique decrease the risk of nerve injury. Avoidance of injury to the superficial sensory branches of the radial and ulnar nerves is absolutely necessary for patient satisfaction. Avoidance of injury to the wound edges with good surgical technique, postoperative immobilization with the wrist in an extended position, and subsequent advancement of the wrist to a neutral position for several weeks decrease the risk of wound dehiscence. Avoidance of excessive skin excision and prolonged wrist immobilization lowers the risk of decreasing range of motion. There have been no complications in patients who underwent this procedure.     

A demonstration of validity of 3-D video motion analysis method for measuring finger flexion and extension

This study demonstrates the validity of using 3-D video motion analysis to measure hand motion. Several researchers have devised ingenious methods to study normal and abnormal hand movements. Although very helpful, these earlier studies are static representations of a dynamic phenomenon. Despite the many studies of hand motion using scientifically impeccable techniques, little is known about digital motion, and there are still few researchers investigating dynamic three-dimensional motion of the hand. Results from a three-camera video motion analysis system were compared to those from the "gold standard", 2-D lateral view fluoroscopy. We used these two methods to record hand motion simultaneously during unrestricted flexion and extension of the index finger of the dominant hand in 6 neurologically normal, healthy volunteers. After collection and post-processing, the waveforms of the PIP, DIP and MCP joint angles were compared using the adjusted coefficient of multiple determination (R2(a), or CMD). The mean CMD values for the MCP, PIP and DIP joint angle waveforms were 0.96, 0.98 and 0.94, respectively, suggesting a close similarity between motion of comparable joints analyzed by the 2-D and 3-D methods. This shows that the method of 3-D motion analysis is capable of accurately quantifying digital joint motion. It is anticipated that 3-D motion analysis, in addition to being used as a research tool, will also have clinical applications such as surgical planning in neuromuscular disorders and the documentation of abnormal motion in many other pathological hand conditions.     

Ex vivo gene therapy cures a blistering skin disease

A recent publication that describes gene therapy treatment of a patient with an inherited blistering skin disease, epidermolysis bullosa, demonstrates for the first time that gene therapy can cure a disease of solid tissue. The treatment relies on ex vivo transduction of autologous epidermal stem cells with a normal copy of the defective gene, followed by reconstitution of the patient's skin with epithelial sheets that are grown from these genetically corrected cells. This approach holds promise for treatment not only of inherited disorders of the skin but also of other solid tissues that are becoming amenable to tissue engineering.     

A demonstration of the validity of a 3-D video motion analysis method for measuring finger flexion and extension

This study demonstrates the validity of using 3-D video motion analysis to measure hand motion. Several researchers have devised ingenious methods to study normal and abnormal hand movements. Although very helpful, these earlier studies are static representations of a dynamic phenomenon. Despite the many studies of hand motion using scientifically impeccable techniques, little is known about digital motion, and there are still few researchers investigating dynamic three-dimensional motion of the hand. Results from a three-camera video motion analysis system were compared to those from the “gold standard”, 2-D lateral view fluoroscopy. We used these two methods to record hand motion simultaneously during unrestricted flexion and extension of the index finger of the dominant hand in 6 neurologically normal, healthy volunteers. After collection and post-processing, the waveforms of the PIP, DIP and MCP joint angles were compared using the adjusted coefficient of multiple determination (R²_a, or CMD). The mean CMD values for the MCP, PIP and DIP joint angle waveforms were 0.96, 0.98 and 0.94, respectively, suggesting a close similarity between motion of comparable joints analyzed by the 2-D and 3-D methods. This shows that the method of 3-D motion analysis is capable of accurately quantifying digital joint motion.

It is anticipated that 3-D motion analysis, in addition to being used as a research tool, will also have clinical applications such as surgical planning in neuromuscular disorders and the documentation of abnormal motion in many other pathological hand conditions.     

Generation of 3D Skin Equivalents Fully Reconstituted from Human Induced Pluripotent Stem Cells (iPSCs)

Recent generation of patient-specific induced pluripotent stem cells (PS-iPSCs) provides significant advantages for cell- and gene-based therapy. Establishment of iPSC-based therapy for skin diseases requires efficient methodology for differentiating iPSCs into both keratinocytes and fibroblasts, the major cellular components of the skin, as well as the reconstruction of skin structures using these iPSC-derived skin components. We previously reported generation of keratinocytes from human iPSCs for use in the treatment of recessive dystrophic epidermolysis bullosa (RDEB) caused by mutations in the COL7A1 gene. Here, we developed a protocol for differentiating iPSCs into dermal fibroblasts, which also produce type VII collagen and therefore also have the potential to treat RDEB. Moreover, we generated in vitro 3D skin equivalents composed exclusively human iPSC-derived keratinocytes and fibroblasts for disease models and regenerative therapies for skin diseases, first demonstrating that iPSCs can provide the basis for modeling a human organ derived entirely from two different types of iPSC-derived cells.     

Fist position for skin grafting on the dorsal hand: II. Clinical use in deep burns and burn scar contractures

The fundamental problem in all types of hand burns is a loss of skin and subsequent deformities. The goal of skin grafting on the dorsal hand is to graft a sufficient amount of skin, as much as the original amount, and to restore normal hand function without secondary deformities. The safe, or Michigan, position commonly has been used for immobilizing the hand. However, this position is to protect hand function rather than to provide for adequate skin grafting. This institution has developed a new hand position (the fist position) for grafting the greatest amount of skin on the dorsal side of the hand. In the fist position, the hand is positioned flexing all joints of the wrist and the fingers and maximally stretching the dorsal surface of the hand before skin grafting. Ten hands with deep second- or third-degree burn (n = 6) and burn scar contracture (n = 4) of the dorsal hand in eight patients were treated with split-thickness skin grafting after immobilizing in the fist position. The burns and contractures involved nearly the total area of the dorsal hand. The hand was kept in the fist position for 7 to 9 days after skin grafting. Excellent functional and cosmetic results were observed in all cases during the follow-up period of 6 months to 2 years. Complications resulting from hand immobilization for a short period did not occur. The fist position may be a proper hand position for skin grafting to reconstruct the dorsal hand.     

Effects of rehabilitative interventions on pain, function and physical impairments in people with hand osteoarthritis: a systematic review

Introduction

Hand osteoarthritis (OA) is associated with pain, reduced grip strength, loss of range of motion and joint stiffness leading to impaired hand function and difficulty with daily activities. The effectiveness of different rehabilitation interventions on specific treatment goals has not yet been fully explored. The objective of this systematic review is to provide evidence based knowledge on the treatment effects of different rehabilitation interventions for specific treatment goals for hand OA.

Methods

A computerized literature search of Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), ISI Web of Science, the Physiotherapy Evidence Database (PEDro) and SCOPUS was performed. Studies that had an evidence level of 2b or higher and that compared a rehabilitation intervention with a control group and assessed at least one of the following outcome measures - pain, physical hand function or other measures of hand impairment - were included. The eligibility and methodological quality of trials were systematically assessed by two independent reviewers using the PEDro scale. Treatment effects were calculated using standardized mean difference and 95% confidence intervals.

Results

Ten studies, of which six were of higher quality (PEDro score >6), were included. The rehabilitation techniques reviewed included three studies on exercise, two studies each on laser and heat, and one study each on splints, massage and acupuncture. One higher quality trial showed a large positive effect of 12-month use of a night splint on hand pain, function, strength and range of motion. Exercise had no effect on hand pain or function although it may be able to improve hand strength. Low level laser therapy may be useful for improving range of motion. No rehabilitation interventions were found to improve stiffness.

Conclusions

There is emerging high quality evidence to support that rehabilitation interventions can offer significant benefits to individuals with hand OA. A summary of the higher quality evidence is provided to assist with clinical decision making based on current evidence. Further high-quality research is needed concerning the effects of rehabilitation interventions on specific treatment goals for hand OA.     

Treatment of the painful neuroma by neuroma resection and muscle implantation

The successful treatment of the painful neuroma remains an elusive surgical goal. This report evaluates one approach to the management of this problem which entails neuroma excision and placement of the proximal end of the nerve away from denervated skin, away from tension, and into a well-vascularized environment: muscle. Seventy-eight neuromas in 60 patients with a mean follow-up of 31 months (range 18 to 43 months) were evaluated. Sixty-seven percent of these patients involved Workmen's Compensation and 57 percent had had at least one previous operation to treat their pain. The results demonstrated good to excellent results in 82 percent of the treated nerves in the entire group. Factors that were predictive of a poorer outcome were (1) digital neuroma (p less than 0.0005), (2) Workmen's Compensation (p less than 0.01), and (3) three or more previous operations for pain (p less than 0.01). Transposition of nerves into small superficial muscles or muscles with significant excursion resulted in treatment failures. The etiology and histopathology of treatment failures are reviewed. Treatment of radial sensory neuromas by transposition of the radial sensory nerve into the brachioradialis muscle when any associated injury to the lateral antebrachial cutaneous nerve was also treated, gave good to excellent relief of pain, and improved hand function in 88 percent of the patients.     

Three Novel Homozygous Point Mutations and a New Polymorphism in the COL17A1 Gene: Relation to Biological and Clinical Phenotypes of Junctional Epidermolysis Bullosa

Junctional epidermolysis bullosa (JEB) is a clinically and biologically heterogeneous genodermatosis, characterized by trauma-induced blistering and healing without scarring but sometimes with skin atrophy. We investigated three unrelated patients with different JEB phenotypes. Patients 1 and 2 had generalized atrophic benign epidermolysis bullosa (GABEB), with features including skin atrophy and alopecia. Patient 3 had the localisata variant of JEB, with predominantly acral blistering and normal hair. All patients carried novel homozygous point mutations (Q1016X, R1226X, and R1303Q) in the COL17A1 gene encoding collagen XVII, a hemidesmosomal transmembrane component; and, therefore, not only GABEB but also the localisata JEB can be a collagen XVII disorder. The nonsense mutations led to drastically reduced collagen XVII mRNA and protein levels. In contrast, the missense mutation allowed expression of abnormal collagen XVII, and epidermal extracts from that patient contained polypeptides of normal size, as well as larger aggregates. The homozygous nonsense mutations in the COL17A1 gene were consistent with the absence of the collagen from the skin and with the GABEB phenotype, whereas homozygosity for the missense mutation resulted in expression of aberrant collagen XVII and, clinically, in localisata JEB.     

马来酸桂哌齐特与腹部带蒂皮瓣对上肢烧伤组织缺损的修复效果

目的：探讨马来酸桂哌齐特联合腹部带蒂皮瓣治疗手及前臂皮肤软组织烧伤缺损的临床效果。方法：选取我院2011 年2 月 -2013 年2 月收治的68 例手及前臂皮肤软组织烧伤缺损患者作为观察组,行马来酸桂哌齐特结合腹部带蒂皮瓣治疗,另选择同 期接受股前外侧皮瓣修复治疗的50 例患者为对照组。观察并比较两组患者皮瓣修复效果以及神经功能烧伤缺损评分。结果：观 察组患者皮瓣存活率高于对照组,差异具有统计学意义(P<0.05);观察组皮瓣感染率低于对照组,差异具有统计学意义(P<0.05); 观察组皮瓣断蒂时间及神经功能烧伤缺损评分均低于对照组,差异具有统计学意义(P<0.05)。结论：马来酸桂哌齐特结合腹部带 蒂皮瓣治疗具有皮瓣存活率高、神经功能恢复良好,术后恢复快等特点,值得临床推广应用。     

The radial forearm skin graft-fascial flap

The radial forearm flap has become a versatile flap for upper extremity reconstruction. The use of the forearm flap for hand reconstruction in the patient with previously burned forearms has not been widely appreciated. In those patients whose forearms have been previously split-thickness skin-grafted on fascia, we have employed the reverse radial forearm flap as a skin graft-fascial flap for hand reconstruction and have obtained excellent functional results. Three patients at various intervals postburn are presented to demonstrate use of this flap for wrist contracture release, coverage of arthroplasties, first web space contracture release, and acute salvage of phalanges and tendons. Assessment of the hand's vascular anatomy and careful treatment of the donor area have contributed to no added morbidity and an excellent aesthetic result at the donor site.     

Management of squamous cell carcinoma in a patient with dominant-type epidermolysis bullosa dystrophica: a surgical challenge

Epidermolysis bullosa dystrophica is a rare congenital skin disease inherited either as a recessive or dominant form, the latter form being less common and much less severe. Squamous cell carcinoma is a rare complication in the dominant form of the disease, only three such cases being reported before, making this case the fourth known case. Although the squamous cell carcinoma is well-differentiated by histopathology, it has a poor prognosis owing to its invasiveness, distant metastases, and multicentricity. Its management also poses a great challenge to the surgeon and personnel involved in patient care. A complete outline of the total management of such a case is described with some interesting observations not mentioned previously in the literature. All the previous three patients are deceased, and this is the only known surviving patient.     

Revertant mosaicism in skin: natural gene therapy

Revertant mosaicism is a naturally occurring phenomenon involving spontaneous correction of a pathogenic mutation in a somatic cell. Recent studies suggest that it is not a rare event and that it could be clinically relevant to phenotypic expression and patient treatment. Indeed, revertant cell therapy represents a potential 'natural gene therapy' because in vivo reversion obviates the need for further genetic correction. Revertant mosaicism has been observed in several inherited conditions, including epidermolysis bullosa, a heterogeneous group of blistering skin disorders. These diseases provide a useful model for studying revertant mosaicism because of the visual and accessible nature of skin. This overview highlights the latest developments in revertant mosaicism and the translational implications germane to heritable skin disorders.