Erfolgreiche Therapie eines Ulcus cruris rheumaticum mit systemischen Immunglobulinen

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. Leg ulcers in rheumatoid arthritis may be caused by vasculitis and are an interdisciplinary therapeutic challenge. A 69 year old women with rheumatoid arthritis and many other medical problems presented with widespread vasculitis-induced therapy-resistant ulceration on her right lower leg. Since previous therapeutic efforts had a negative effect on wound healing, we administered intravenous immunoglobulins which led to complete healing of the ulcer was achieved. Both the serological and rheumatologic features of her rheumatoid arthritis also improved. Intravenous immunoglobulins represented an effective therapeutic option with fewer side effects in the therapy of vasculitis-induced leg ulceration in this patient with rheumatoid arthritis.     

Basic fibroblast growth factor treatment for skin ulcerations in scleroderma

We report the use of topical application of recombinant human basic fibroblast growth factor (rhbFGF) to successfully treat therapy-resistant, chronic leg ulcers in scleroderma. Endothelial cell FGF receptors are directly stimulated by bFGF; also, bFGF promotes the regeneration of capillary-rich granulation tissue. We conclude that topical bFGF may be a powerful new pharmacologic tool for treating severe skin ulcers.     

Prolidase deficiency: the use of topical proline for treatment of leg ulcers

A 41-year-old man with prolidase deficiency has had chronic leg ulcers and recurrent cellulitis for most of his life. Until recently he had been hospitalized at least annually for this and suffered significant morbidity as a result. Since commencing topical 5% proline in white soft paraffin ointment to treat the leg ulcers, there has been marked improvement in the ulcers and decreased frequency of hospitalizations for cellulitis. This lends further support to the use of topical proline in the treatment of patients with skin ulcers secondary to prolidase deficiency.     

Resolution of a leg ulcer after hysterectomy for huge uterine myoma

Venous ulcers are the most common type of leg ulcers, accounting for 80% to 90% of cases. We report a large, therapy-resistant ulcer present for three months on the right leg of a 44-year-old woman who also had a huge uterine myoma. Without any other treatment, the leg ulcer regressed spontaneously three months after a hysterectomy for the uterine myoma that had been demonstrated in a CT image to be compressing the right common iliac vein in the pelvis. Uterine myoma can become the cause of venous insufficiency of the leg, when it is big enough to disturb the blood circulation in the pelvis in individuals who have incompetent perforating veins.     

The role of vascular surgery in chronic leg ulcers: report from a specialized ulcer clinic

Experience gained from cooperation between dermatologists and vascular surgeons in 177 patients evaluated at a joint leg ulcer clinic is reported. Patients were divided into two subgroups: (i) 86 patients with healed ulcers and (ii) 91 patients with ongoing therapy-resistant ulcers. Venous insufficiency was the most common etiology in both subgroups (87% and 55%, respectively). Of previous therapy-resistant ulcers, 71% were healed after the combined effort. The pattern of venous incompetence differed between the two subgroups; patients with isolated superficial disease constituting 68% and 26% of patients, respectively. In patients with therapy-resistant ulcers, those with isolated superficial venous insufficiency were found to have a better prognosis than those with deep venous insufficiency. Cooperation between the dermatologist and vascular surgeon is a mainstay in order to take advantage of the possibilities offered by modern vascular surgery.     

Squamous Cell Carcinoma Developing in Epidermolysis Bullosa Dystrophica

Two patients with epidermolysis bullosa dystrophica recessiva who had squamous cell carcinoma are presented. Case 1 is a 40-year-old woman who had ulcers on her left lower leg. Case 2 is a 42-year-old man who had a tumor on his left first toe. Wide surgical excision with skin coverage by autograft was performed in case 1. Amputation of the toe in case 2 was performed. A review of the cases of epidermolysis bullosa dystrophica associated with cancer reported in Japan is also presented.     

A retrospective review of 20 hypertensive leg ulcers treated with mesh skin grafts

BACKGROUND: Few articles have been published about hypertensive leg ulcers and their surgical treatment. Since mid of the year 2000, it has been our policy to treat all hypertensive leg ulcers very early with mesh split-thickness skin grafts. The present series consists of 15 patients whose hypertensive leg ulcers, including five bilateral cases, were treated with 20 mesh grafts from 2000 to 2002. SUBJECTS AND METHODS: All patients, nine women and six men, had a long history of hypertension. The same surgical procedure was applied to all 15 patients: a complete mechanical debridement of all necrotic tissues, immediately followed by mesh skin grafting. RESULTS: Patients were discharged from the hospital after an average post-operative period of 16 days. Upon leaving the hospital, the patients had lesions completely healed in 14 of 20 cases. The graft take had been complete after an average period of 14 days. In six cases, one or two very small patches of skin graft had necrosed and complete healing required an additional period of 1 to 3 months. In all 20 cases, pain had disappeared within 1 week from surgery. DISCUSSION: All patients were on opioid therapy before surgery. With medical treatment only, hypertensive leg ulcers used to heal after a mean period of 15 months. After surgery, the average healing period was 2 weeks and opioids were stopped within 1 month after surgery. CONCLUSION: The review of the present series shows that early mesh grafting of hypertensive leg ulcers is beneficial, because healing is very quick and the pain will disappear quasi-instantly.     

Reactions to Penicillamine: A Case of Cutis Laxa,Elastosis Perforans Serpiginosa and “Pseudo” Pseudoxanthoma

This patient was a 61‐year‐old white female who received several years of penicillamine therapy for the treatment of cystinuria. She subsequently developed penicillamine induced cutis laxa, elastosis perforans serpiginosa, and pseudoxanthoma elasticum like skin lesions. In addition, she suffered from numerous chronic bilateral lower extremity skin ulcerations. Her past medical history was also significant for end stage renal disease requiring hemodialysis and pulmonary fibrosis. She presented to the University of Miami Wound Care Center in 1/04 for treatment of her chronic ulcerations. On physical examination, the patient had multiple large hyperpigmented plaques with central ulcerations on her lower extremities. Some of the ulcers had overlying crust and others were covered with yellow fibrinous tissue. She also had generalized thickened, lax skin with multiple folds. On her neck, thighs, back and arms were violaceous, atrophic, serpiginous plaques with peripheral crusted erosions. A biopsy taken from the patients left thigh revealed dermal elastosis and the features of pseudo‐pseudoxanthoma. Two additional biopsies taken from the left thigh demonstrated elastosis perforans serpiginosa. This case highlights multiple skin manifestations of penicillamine therapy.     

Erythroderma as a paraneoplastic cutaneous disorder in systemic anaplastic large cell lymphoma

Background Paraneoplastic cutaneous disorders (PCDs) or dermadromes are skin conditions that have an association with internal malignancies but are not themselves malignant. We report the first two cases of systemic anaplastic large cell lymphoma (s‐ALCL) accompanied by erythroderma and multiple leg ulcers as PCDs. Case 1. A 52‐year‐old Japanese man presented with disseminated itchy papular erythemas which he had over his entire body for the preceding 5 years that later exacerbated to erythroderma. Multiple punched‐out ulcers also developed on his lower legs. Superficial lymph nodes (LNs) were swollen, and a left axillary LN biopsy demonstrated dense CD30⁺ atypical large cell (ALC) infiltration. By contrast, lymphocytes infiltrating into the erythroderma and leg ulcers were CD30^?, and T‐cell receptor β (TCRβ) chain gene rearrangement was negative in skin biopsy specimens. Thus, he was diagnosed with s‐ALCL. Not only his s‐ALCL but also his erythroderma and leg ulcers responded well to chemotherapy. Case 2. A 71‐year‐old Japanese woman presented with erythroderma that persisted for approximately 20 years after mastectomy. At her initial hospital visit, she was diagnosed with s‐ALCL by biopsy of swollen left inguinal LNs. Similar to Case 1, CD30⁺ ALCs were negative in skin samples with normal TCRβ chain gene rearrangement. As the erythrodermic skin lesion responded well to chemotherapy for s‐ALCL, it was considered a PCD. Conclusion s‐ALCL development may be predicted by the precedence and concurrence of intractable paraneoplastic erythrodermic and ulcerative skin lesions, as reported in our two cases.     

Tissue-engineered skin in the healing of wound stumps from limb amputations secondary to purpura fulminans

Currently wound treatment options of amputation stumps due to purpura fulminans include healing by secondary intention from wound debridement, split-thickness skin grafting, tissue and muscle flaps, plantar skin free transfer, skin expansion, artificial skin, and hyperbaric oxygen therapy. We saw a 6-month-old girl with purpura fulminans as a complication of meningococcemia. She developed necrosis of the distal extremities resulting in bilateral amputation of the lower limbs. Shortly thereafter the leg stumps also became necrosed and she underwent unsuccessful split-thickness grafts of lower limb ulcers. The patient's difficult-to-heal wounds made her an excellent candidate for treatment with tissue-engineered skin. At 10 months of age, this was applied to her previously nonhealing wounds. The tissue-engineered skin induced rapid healing of the patient's chronic amputation stump ulcers and provided her with substantial pain relief. In conclusion, tissue-engineered skin appears to be a potential beneficial treatment for chronic wounds in children with nonhealing amputation stumps.     

Successful treatment of chronic venous leg ulcers with lyophilized cultured epidermal allografts

The case of a 67-year-old woman with chronic venous leg ulcers and severe gonarthrosis is described. In spite of intensive therapy, the leg ulcers had persisted for 4 years and made the intended orthopaedic operation of the right knee impossible. The patient was treated with lyophilized cultured epidermal allografts and her leg ulcers healed within 40 days. Lyophilized cultured epidermal allografts represent a modern type of active wound dressing that leads to rapid healing of chronic venous leg ulcers and enables patients to undergo surgical intervention.     

A Hydroxyurea-induced Leg Ulcer

Hydroxyurea is a cytostatic agent that has recently become the drug of choice in the treatment of various myeloproliferative diseases. The cutaneous side effects of hydroxyurea include xerosis, hyperpigmentation, nail discoloration, and scaling. Leg ulcers have only rarely been reported in association with hydroxyurea treatment. A 75-year-old woman presented with leg ulcers, nail discoloration, and xerosis. The leg ulcers were refractory to conventional treatment. She had been taking oral hydroxyurea since being diagnosed with essential thrombocytosis in 2002. Hence, we suspected hydroxyurea-induced leg ulcers and discontinued her hydroxyurea treatment; the ulcers gradually healed thereafter. We present a rare case of hydroxyurea-induced leg ulcers in Korea.     

Leg ulcers and hydroxyurea: report of three cases with essential thrombocythemia

CASE 1: A 65-year-old woman with essential thrombocythemia (ET) had been taking oral hydroxyurea (HU), 1,000 mg daily, for 7 years. Six months ago, she developed an ulcer on the outer part of her left ankle, which healed spontaneously within 2 months. She presented with a new, tender, shallow ulcer, 2 cm x 2 cm in size, at the same site. Doppler examination revealed thrombosis of the left common femoral vein and a calcified atheroma plaque of the left common femoral artery. The dosage of HU was decreased to 500 mg daily when the platelet counts were found to be within normal levels. The ulcer completely healed within 2 months with occlusive wound dressings, and has not recurred within the follow-up period of 1 year. CASE 2: A 56-year-old women presented with multiple, painful, leg ulcers of 1 year duration. She had been diagnosed as having ET and had been on HU therapy, 1,500 mg/day, for the past 5 years. Interferon-alpha-2b was started 3 months ago, in addition to HU, which was tapered to 1,000 mg daily. She had suffered from hypertension for 20 years treated with nifedipine and enalapril, and had recently been diagnosed with diabetes mellitus which was controlled by diet. Examination revealed three ulcers located on the lateral aspects of both ankles and right distal toe. Arterial and venous Doppler examinations were within normal limits. Histopathology of the ulcer revealed nonspecific changes with a mixed inflammatory cell infiltrate around dermal vessels. The ulcers completely healed within 10 weeks with topical hydrocolloid dressings. After healing, she was lost to follow-up. A year later, it was learned that she had developed a new ulcer at her right heel, 3 months after her last visit (by phone call). This ulcer persisted for 8 months until HU was withdrawn. CASE 3: A 64-year-old woman with ET presented with a painful leg ulcer of 6 months' duration. She had been taking oral HU for 5 years. She had a 20-year history of hypertension treated with lisinopril. Examination revealed a punched-out ulcer of 2 cm x 2 cm over the right lateral malleolus. Doppler examination of the veins revealed insufficiency of the right greater saphenous and femoral veins. Angiography showed multiple stenoses of the right popliteal and femoral arteries. As her platelet count remained high, HU was continued. During the follow-up period of 13 months, the ulcer showed only partial improvement with local wound care.     

High sensitization rate to emulsifiers in patients with chronic leg ulcers

Emulsifiers are common constituents of most topical preparations. To study the sensitization rate in a population with frequent use of these agents, we selected 47 patients with chronic or recurrent (> 1 year) inflammatory skin disease (leg ulcers, contact dermatitis, atopic dermatitis, psoriasis) for patch testing with the following emulsifiers: Tween 40 (polyoxyethylene sorbitan monopalmitate), Tween 80 (polyoxyethylene sorbitan monooleate), Span 60 (sorbitan monostearate), Span 80 (sorbitan monooelate), Ariacel 83 (sorbitan sesquioleate), Atlas G 2162 (polyoxyethylene oxypropylene stearate), Atlas G 1441 (polyoxyethylene sorbitol lanolin derivative), triethanolamine, Lanette O (cetylstearyl alcohol), Lanette N. 12 patients had at least 1 positive reaction (25.5%) at 3 or 4 days. Among them, 10 had leg ulcers (43.4% of the leg ulcer group), and 2 had contact dermatitis (13.3% of the contact dermatitis group). No positive reaction was observed in the other patients. When the patients were tested with their own topical preparations or wound dressings, 6 of them, all with leg ulcers, had positive reactions. These results show a surprisingly high prevalence of sensitization to emulsifiers in patients with chronic leg ulcers, in contrast to patients with other inflammatory skin diseases.     

Genital pyoderma gangrenosum: Report of two cases and published work review of Japanese cases

Pyoderma gangrenosum is an ulcerative skin disorder showing characteristic non‐infectious ulcers and affects the lower extremities in approximately 70% of cases. Pyoderma gangrenosum is commonly associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis and hematological malignancies. Herein, we report two cases of Japanese patients diagnosed with genital pyoderma gangrenosum. Case 1 was a 74‐year‐old woman without associated systemic complications, whose skin lesion resembled a squamous cell carcinoma and was limited to the vulva. Case 2 is an 89‐year‐old man, who suffered from myelodysplastic syndrome and acute myeloid leukemia, and presented with penile and leg ulcers mimicking pressure sores. Both cases responded well to systemic steroids. We review 13 genital pyoderma gangrenosum cases (76.9% male; aged 30–89 years) from 1996 to 2012 in Japan, including 11 previously reported cases and the present study's two cases. Four of the 13 genital pyoderma gangrenosum cases had associated systemic diseases and their skin lesions spread to the extragenital areas. Eight of the remaining nine genitalia‐localized pyoderma gangrenosum cases had no associated systemic diseases. In conclusion, genital pyoderma gangrenosum is rare and may be misdiagnosed. It should therefore be considered in cases of refractory genital ulcers. In addition, genitalia‐localized pyoderma gangrenosum tends to be without systemic complications.     

Elevated expression of extracellular matrix metalloproteinase inducer (CD147) and membrane-type matrix metalloproteinases in venous leg ulcers

BACKGROUND: Matrix metalloproteinases (MMPs) contribute to matrix remodelling in venous leg ulcers. Extracellular MMP inducer (EMMPRIN; CD147) has been reported to increase MMP expression, and membrane type 1 MMP (MT1-MMP) has been implicated in the activation of MMPs. OBJECTIVES: To examine whether and to what degree EMMPRIN, MMP-2, MT1-MMP and membrane type 2 MMP (MT2-MMP) are expressed in venous leg ulcers as well as the association with MMP activity. METHODS: EMMPRIN, MMP-2, MT1-MMP and MT2-MMP were analysed by zymography and immunohistochemistry in biopsies from healthy skin and lesional tissue from venous leg ulcers. RESULTS: Zymography provided direct evidence of increased proteolytic activity of MMP-2 in lesional skin in comparison with healthy controls. Immunostaining showed intense expression of EMMPRIN, MMP-2, MT1-MMP and MT2-MMP in dermal structures of venous leg ulcers, whereas only EMMPRIN and MMP-2 showed elevated expression in perivascular regions. Our findings indicate that venous leg ulcers are characterized by elevated expression of EMMPRIN, MMP-2, MT1-MMP and MT2-MMP. The immunohistological findings of skin alterations reflect the dynamic process of activation of soluble and membrane-bound MMPs, which may be highly induced by EMMPRIN. CONCLUSIONS: These data suggest for the first time that membrane-bound MMPs may favour enhanced turnover of the extracellular matrix and support unrestrained MMP activity in venous leg ulcers.     

Cultured allogeneic skin cells are effective in the treatment of chronic diabetic leg and foot ulcers.

Diabetic ulcers on the lower extremities present a difficult treatment problem, and some ulcers respond poorly to conventional topical and cast treatment. The purpose of this study was to assess the effect of cultured allogeneic keratinocyte epithelium and fibroblast-gelatin sponge on the healing of chronic, refractory diabetic leg and foot ulcers. Non-diabetic chronic leg ulcers were treated for comparison. This open study comprised 22 patients with type I or type II diabetes and 16 patients with leg or ankle ulcers of different aetiologies. A total of 26 diabetic and 25 non-diabetic ulcers were treated mainly with keratinocyte epithelium and/or fibroblast-gelatin sponge once weekly until complete healing or until no further healing could be observed despite several repeated treatments. The duration of diabetic ulcers was 10.3+/-15.8 (mean+/-SD) months and the size 3.1+/-6.6 cm2. The diabetic ulcers were located in the heel (7), toe (7), sole (5), leg (6) and Achilles (1). The mean duration of non-diabetic ulcers was 6.8+/-6.0 months and the size 10.5+/-11.8 cm2. A total of 12+/-11 skin cell transplantations were performed for the diabetic ulcers. All but 1 diabetic ulcer healed during the study. The time for 50% reduction in ulcer area was 32+/-32 days, but 99+/-110 days were needed for complete ulcer closure. The longer the ulcer had existed the longer was the healing time. Heel ulcers showed significantly slower healing response than leg, sole and toe ulcers. Preliminary results suggest that both keratinocytes and fibroblasts are equally effective in the healing process. The time required for healing of the diabetic ulcers did not differ markedly from that of the non-diabetic ulcers. The results suggest that cultured allogeneic skin cells used once weekly are effective in the treatment of recalcitrant diabetic ulcers.     

The longevity of a bilayered skin substitute after application to venous ulcers

BACKGROUND: A bilayered skin substitute composed of allogeneic keratinocytes and fibroblasts in a collagen gel has been approved by the US Food and Drug Administration for the treatment of venous and diabetic ulcers. Its mechanism of action has not been fully determined. OBJECTIVE: To determine the longevity of allogeneic fibroblasts and keratinocytes in a bilayered skin substitute in patients with venous leg ulcers. METHODS: Ten patients with venous leg ulcers were treated with a bilayered skin substitute on day 0, days 3 to 5, and weeks 1 through 3. Biopsy specimens of the grafted wound were taken. We used polymerase chain reaction analysis to determine whether allogeneic DNA was present in the biopsy specimens. RESULTS: We detected allogeneic DNA in 2 of 8 specimens at 1 month after initial grafting. Neither of the 2 patients showed persistence of allogeneic DNA at 2 months after initial grafting. CONCLUSIONS: Allogeneic cells from a bilayered skin substitute do not appear to survive permanently after grafting for treatment of venous leg ulcers. Other mechanisms of action might include cytokine release, structural support, or provision of a moist wound environment.     

Neonatal lupus erythematosus in identical twins, showing transient bullous lesions

Abstract: One of identical twin girls was born with ulcers on her leg, and shortly after birth developed a flaccid blister on the leg. Subepidermal blister with vacuolar degeneration of basal cell layer and the heavy infiltration of mononuclear cells in the upper dermis were observed in the blister lesion. She also had generalized livedo. Her identical twin sister did not exhibit ulcers or blisters, but was born with milia on her limbs. Their mother was found to have lupus erythematosus with positive anti‐Ro/SSA antibodies and developed Sjögren syndrome. We emphasize neonatal blistering and congenital milia unique manifestations of neonatal lupus erythematosus.