Intractable Diffuse Alopecia Caused by Multifactorial Side‐Effects in Treatment of Acute Lymphocytic Leukemia: Connection to Iatrogenic Failure of Estrogen Secretion

Abstract: Treatment of infantile acute lymphocytic leukemia (ALL) may cause failure to thrive and hypogonadism due to hypopituitarism induced by chemotherapy and whole‐brain radiotherapy. We report the case of a 22‐year‐old girl with a genetic predisposition to pattern hair loss who developed inveterate diffuse alopecia. The patient had onset of ALL at 8 years old and underwent bone marrow transplantation (BMT). Diffuse alopecia gradually advanced over her whole body. Her vellus scalp hair gradually came out, and hair loss progressed again at 8 years, after BMT. She later developed iatrogenic failure of secretion of estrogen and was treated with estrogen substitution therapy for 14 months from the age of 20. There was a small increase in the volume of hair during therapy, but alopecia returned to the former level after the therapy was suspended. Histopathologic examinations of the scalp performed during estrogen substitution therapy and 2 years after suspension of the therapy showed a 60% decrease in the number of hair follicles and prominent development of vellus hair. We conclude that estrogen influenced hair growth in the context of a genetic predisposition for pattern hair loss in this case.     

胰岛素强化治疗对重症胰腺炎的临床疗效研究

目的探讨胰岛素强化治疗对于急性重症胰腺炎（SAP）的疗效。方法2004年6月-2010年6月134例SAP患者随机分为对照组,胰岛素强化治疗组。对照组给予常规治疗,治疗组在常规治疗基础上给予胰岛素持续泵入。观察两组治疗前、后白细胞计数、血淀粉酶、血清白蛋白、动脉血氧分压以及肠道功能恢复时间、住院时间及病死率。结果与对照组比较采用胰岛素强化治疗后,可显著降低第3、5、7、14天自细胞计数（P〈0．05）、血淀粉酶（P〈0．01）;显著提高治疗后3、5、7、14天的血清白蛋白水平（P〈0．01）,显著提高第3、5、7天动脉血氧分压（P〈0．01）;显著缩短肠道功能恢复时间、减少住院时间、降低病死率（P〈0．01）。结论胰岛素强化治疗可显著改善急性重症胰腺炎的疗效,缩短住院时间,降低病死率。     

胰岛素抵抗黑棘皮病伴增殖性皮炎样表现一例

报告1例具有胰岛素抵抗黑棘皮病伴增殖性皮炎样表现.患者女,11岁,4岁开始肥胖,表现为双手足背、腹股沟境界清楚的肥厚性红斑,上有增殖性损害,颈、腋窝、腹股沟等处灰黑色色素沉着,长期以湿疹治疗无效.入院后内分泌检查提示高胰岛素血症和胰岛素抵抗,考虑为伴胰岛素抵抗的黑棘皮病的特殊皮损表现.经饮食、运动治疗后无效,给予二甲双胍治疗后症状好转.     

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.     

Post‐erysipela panniculitis ossificans of the lower leg treated with pentoxifylline

We report the case of a female patient who developed a firm, wooden‐like, nonpitting edema of the left lower leg after a dermo‐hypodermitis. The clinical picture was accompanied by intense pain, strongly impacting the patient's quality of life. A soft‐tissue ultrasound demonstrated several millimetric hyperechoic linear lesions whose histopathological examination was conclusive for panniculitis ossificans. A conservative medical management with compression stockings associated with pentoxifylline 800 mg/day was prescribed with improvement of the edema and, in particular, a good pain control. To date, after a 2‐year therapy with pentoxifylline, the leg wooden‐like edema has substantially improved, despite the persistence of the well‐known foci of ossification, and the pain has resolved, conditioning a substantial improvement of the patient's quality of life. No side effect has been observed during the routine follow up. Although there is no unanimous opinion in the literature about the effect of pentoxifylline on bone formation and osteogenic differentiation, pentoxifylline treatment proved to be beneficial in our patient both for the heterotopic ossification process and the pain control. We collected some of the data in literature about pentoxifylline effects and advanced some hypotheses to explain our results. Finally, we suggest that an anti‐inflammatory and vasodilators drug such as pentoxifylline could be a possible alternative in heterotopic ossification disorders.     

Cutaneous allergic accidents caused by insulin. Current aspects apropos of 2 cases

Current data concerning cutaneous allergy to insulin may be illustrated by the two cases reported here. One was a woman with gestational diabetes; she was treated with bovine insulin and developed generalized urticaria which subsided after switching to human insulin. The other was a woman who had pruritus localized to the site of injection with every type of insulin and in whom laboratory examinations showed an increase of specific IgE. Immunological reactions have been described since the time when exogenous insulin was introduced as a treatment of diabetes. The wide use of purified human insulin has considerably reduced their incidence but benign local and immediate systemic reactions are still being reported, their estimated frequency varying from 10 p. 100 to 50 p. 100 of the patients treated. In reality, allergy to insulin itself is extremely rare compared with allergic reactions to preservatives, such as metacresol, additives (protamine and zinc and contaminants present in insulin preparations: desamido-insulin. True allergic reactions to insulin may be localized or generalized and biphasic, and in most cases they are IgE-mediated. Some late local reactions, as well as atrophy, can be ascribed to delayed hypersensitivity. Treatment includes: (i) change in the type of insulin used; (ii) systemic or topical corticosteroid therapy; (iii) antihistamines and aspirin, and (iv) desensitization. The allergic complications of insulin therapy are benign; they usually do not require any particular treatment and often spontaneously regress.     

Immediate and delayed complications of dexamethasone cyclophosphamide pulse (DCP) therapy

Dexamethasone-cyclophosphamide pulse (DCP) is the prefered mode of therapy in pemphigus in India because it is relatively free from the side effects seen with heavy doses of daily oral steroids. One hundred forty-six pemphigus patients treated with DCP were observed for side effects of this regimen. One hundred forty mg of dexamethasone was administered IV in 200 ml of 5% dextrose over a period of 60-90 minutes on 3 consecutive days. Five hundred mg of cyclophosphamide was added on first day of the pulse and 50 mg given orally daily in the intervening period. DCP was repeated every 4 weeks and continued for 6 months after subsidence of the disease (no new lesions). Flushing over the face was the most common event recorded during the adiministration in 78 subjects followed by palpitations in 11, hiccups in 9, and numbness of feet in 6. Fourteen patients had polyurea, and 3 developed skin rash. Shivering, shooting pains along thighs, breathlessness, seizure and unilateral limb edema were observed in one patient each. Generalized weakness/malaise was the most troublesome delayed side effect in 81 (55.4%) patients; it lasted for 8-15 days after the pulse. Thirty-six (24.6%) had inadequate sleep syndrome, 23 (15.7%) had headache, 21 (14.3%) complained of arthralgias, 19 (13%) experienced alteration in taste, and 13 (9%) had diffuse hair loss. 28 females developed menstrual disturbances, and 14 (9.5%) had blurring of vision (glaucoma in 3 and posterior subcapsular cataract in 1). Thirteen of eighteen diabetics had an increase in blood sugar requiring higher doses of insulin. Five NIDDM patients needed insulin. Four (2.7%) developed hypertension. Pulse therapy is not absolutely free from side effects. Hypertension and diabetes occur less frequently as compared to conventional steroid therapy. Generalized weakness, flushing, headache and taste alteration occur exclusively with pulse therapy.     

Large B-cell lymphoma of the leg: clinical and pathologic characteristics in a North American series

BACKGROUND: Large B-cell lymphoma (LBCL) of the leg is an uncommon subset of primary cutaneous B-cell lymphoma that has been described in a series of European patients. OBJECTIVE: Our purpose was to evaluate the clinical manifestation, diagnostic histopathology, immunophenotype, clinical course, and response to treatment of LBCL of the leg. METHODS: We conducted a retrospective case series of 3 patients with primary LBCL of the leg. RESULTS: The 3 elderly patients presented with progressive erythematous nodules on bilateral or unilateral lower extremities. All 3 patients had pre-existing peripheral edema or peripheral vascular disease. Histopathologic examination of the nodules showed dense lymphocytic infiltrates composed predominantly of large dysplastic lymphocytes that marked as B cells (CD20(+)). In 2 cases, the neoplastic cells were BCL-2 positive. All patients responded to initial therapy with localized electron beam radiation and chemotherapy but had disease progression. One patient had a complete and durable second response to anti-CD20 monoclonal antibody (rituximab). CONCLUSIONS: The patients described have similar clinical and histopathologic features to those previously described. There may be an association between LBCL and pre-existing lower-extremity vascular disease. Treatment of LBCL is difficult, but 1 patient responded well to systemic anti-CD20 monoclonal antibody.     

Glucose and insulin responses are improved in patients with psoriasis during therapy with etretinate

Since lipemia is commonly induced by retinoid therapy, we investigated the effects of etretinate administration on glucose metabolism by obtaining five-hour oral glucose tolerance tests in 23 patients before and after 20 weeks of etretinate therapy for psoriasis. Compared with pretreatment values, peak and aggregate levels for serum glucose and aggregate levels for serum insulin were significantly lower during therapy. The changes were not associated with obesity, weight loss during treatment, or pretherapy glucose tolerance or insulin secretion level. Of 11 patients with impaired or diabetic glucose tolerance prior to therapy, eight patients had improved glucose tolerance after 20 weeks of etretinate treatment. Despite inducing hypertriglyceridemia in most patients, etretinate therapy is associated with a reduction in glucose levels in response to a glucose load.     

Aggressive, extensive, vasculitic leg ulceration associated with hydroxyurea therapy and a fatal outcome

The association of lower leg ulcer development and hydroxyurea therapy in patients with myeloproliferative disorders has been reported previously. In most of these cases the ulcers healed with cessation of the hydroxyurea together with meticulous attention to wound care. We report a patient who developed painful vasculitic ulcers secondary to hydroxyurea on both lower legs whilst on long-term hydroxyurea therapy for idiopathic thrombocytosis. The ulcers extended relentlessly despite stopping hydroxyurea, maximizing topical therapies and starting intensive systemic treatment. We discuss the association of hydroxyurea therapy with the development of painful ulceration.     

Steroid atrophy scarring treated with fat grafting in a patient with complex regional pain syndrome: A case report

Subcutaneous atrophy is a known complication of steroid injections. Excellent results with fat grafting for the treatment of steroid atrophy have been documented. However, the benefit of treating steroid-induced subcutaneous atrophy in an extremity diagnosed with complex regional pain syndrome (CRPS) has not been described. CRPS, known formerly as reflex sympathetic dystrophy or RSD, causalgia, or reflex neurovascular dystrophy, is a severe, progressive musculoskeletal pain syndrome characterized by pain which is disproportionate to the severity of the inciting event, edema, or skin changes. Common treatment modalities include pharmacotherapy, physical therapy, and nerve blocks—each therapy producing varying results. We present a literature review of CRPS and the case of a 15-year-old female who developed CRPS of the left lower leg after arthroscopic debridement with retrograde drilling of an osteochondral lesion. Steroid atrophy of the involved area following a saphenous nerve block complicated the patient's treatment course. The area of atrophy was treated with autologous fat grafting. Following the adipose injection procedure, the patient experienced almost complete resolution of her CPRS-associated pain symptoms, along with improved cosmetic appearance of the area.     

Graft-versus-host reaction affecting lesional skin but not normal skin in a patient with piebaldism

Summary A case of graft-vs.-host disease (GVHD) arising solely within an area affected by piebaldism is described. The patient, a 35-year-old woman with a single hypopigmented patch on the right leg present since birth, had received an allogeneic bone marrow transplant (BMT) from an HLA-identical sibling donor, for treatment of a myelodysplastic syndrome (MDS). Beginning on day + 38 post-BMT, the patch developed changes which were histologically consistent with GVHD. Syngeneic mixed epidermal cell-lymphocyte reaction (MECLR) testing of tissue from the patch, and from adjacent normal skin, showed differences which suggest that piebaldism-affected skin is immunologically different from normal skin. These findings may offer new insight into the pathophysiology of this disorder.     

Transfer of vitiligo after allogeneic bone marrow transplantation

Adoptive transfer of donor immunity has been demonstrated in animals after bone marrow transplantation (BMT). In humans, several autoimmune diseases have been similarly transferred. Although BMT may, per se, be associated with a modulation of the recipient's immune system, which could trigger or even cause autoimmune diseases, both animal experiments and experience with humans show the likeliness of adoptive transfer of donor immunity to the recipient. We describe a patient with multiple myeloma in whom generalized vitiligo developed within 3 months after allogeneic BMT from his HLA-matched sister with vitiligo. We believe that a form of adoptive transfer of donor immunity to the recipient might play a role in the development of vitiligo. In spite of this, neither de novo development of vitiligo in a genetically predisposed patient nor autoimmune phenomena associated with graft-versus-host disease can be completely excluded as a contributing factor for development of vitiligo in our patient. To our knowledge, this is the first case report of transfer of vitiligo after BMT from a donor with vitiligo.     

Graft Versus Host Disease with Mixed Chimerism

We report a patient with graft versus host disease (GVHD) with mixed chimerism (MC). The patient had chronic myelogenous leukemia and received bone marrow transplantation (BMT) from his elder sister. Eighty days after BMT, erythematous lesions appeared on his chest. Histological examination from the skin lesion revealed lymphocytic infiltration into the upper dermis. Eosinophilic necrotic keratinocytes were scattered through the epidermis. Liquefaction degeneration was also recognized. Sicca syndrome appeared from 110 days after BMT. Detection of host origin Y-chromosome-specific DNA by polymerase chain reaction (PCR) method in bone marrow and peripheral blood showed that all bone marrow samples obtained 6 months from BMT were positive for Y-specific DNA, while peripheral blood became positive in the 60th month after BMT. The host origin normal karyotype (46,XY) in the bone marrow samples was identified for the first time in the 60th month after BMT. These results indicate that host-origin hematopoietic cells survived after BMT.     

Clinical significance of skin biopsies in the diagnosis and management of graft-vs-host disease in early postallogeneic bone marrow transplantation

OBJECTIVE: To determine the value of skin biopsies in the management of suspected graft-vs-host disease (GVHD) within 30 days of allogeneic bone marrow transplantation (BMT). DESIGN: Retrospective study based on review of a BMT database. SETTING: Leukemia/BMT ward of a tertiary care, university teaching hospital. PATIENTS: One hundred and eighty-seven consecutive patients who received allogeneic BMT between January 1, 1994, and June 30, 1997, at Vancouver General Hospital, Vancouver, British Columbia. MAIN OUTCOME MEASURES: (1) Skin biopsy frequency for patients with rashes suggestive of acute GVHD; (2) clinical significance of skin biopsy in the management of patients with suspected acute GVHD after BMT; (3) relationship between severity of clinical GVHD and the likelihood to receive GVHD therapy; and (4) relationship between biopsy status or biopsy result and outcome of BMT (acute and chronic GVHD, transplant-related mortality, and overall and event-free survival). RESULTS: During the early post-BMT period (<30 days after BMT), 88 patients had rashes suggestive of acute GVHD; of these, 51 (58%) underwent skin biopsy to confirm the diagnosis. Skin biopsies were performed more often for higher clinical stages of cutaneous GVHD. There was no significant difference between the patients with positive biopsy findings and those with negative findings, either in the clinical severity of acute GVHD or in likelihood to receive treatment for GVHD. Most (85%) of the patients who underwent biopsies and received GVHD therapy had treatment initiated before skin biopsies were performed or before the results were available. The higher the clinical grade of overall acute GVHD, the more likely it was that the patients were treated for GVHD (P<.001). The outcome of BMT was not influenced by the skin biopsy status or biopsy result. CONCLUSIONS: The biopsy findings correlated poorly with the clinical severity of skin rash suggestive of acute GVHD soon after BMT. The decision to treat suspected acute GVHD depended not on skin biopsy findings but rather on clinical severity of acute GVHD. In this regard, skin biopsy has a limited role in the management of patients early after allogeneic BMT.     

A case of human insulin allergy induced by short-acting and intermediate-acting insulin but not by long-acting insulin

A 66-year-old woman suffering from pollinosis developed generalized urticaria after injection of intermediate-acting insulin for diabetes mellitus. She had human insulin-specific IgE, and in skin tests was positive for human recombinant insulin and negative for additives. Uniquely, she reacted to fast-acting and slow-acting insulin but not to long-acting insulin. We further confirmed that human insulin preparations could stimulate her peripheral basophils to release a significant amount of histamine. Genetically generated human insulin analogs, aspart and lispro, induced positive skin tests and histamine release from basophils. She was recommended to use a long-acting insulin preparation and was free from symptoms thereafter.     

Primary cutaneous anaplastic large cell lymphoma with subsequent leg involvement

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is regarded as an indolent type of cutaneous T-cell lymphoma. However, a few recent publications revealed that C-ALCL patients with initial leg involvement had significantly worse survival than those without initial leg involvement. Herein, we report a case of C-ALCL with subsequent leg involvement, which led to death after chemoradiation therapy. A 75 years old Japanese man presented with multiple erythematous nodules in his left arm and the side of his left chest. Histopathological and immunohistochemical studies led to the diagnosis of primary C-ALCL. At the initial diagnosis, no leg lesion was found. One year after the initial diagnosis, C-ALCL appeared in his right lower thigh and left hip. Radiation therapy, low-dose etoposide and CHOP therapy were performed; however, the patient died of malignant lymphoma 4 years after the initial diagnosis. We speculated that the occurrence of subsequent leg involvement may also be indicative of a worse prognosis, as in the case with initial leg involvement in C-ALCL. Therefore, we propose that C-ALCL patients with initial or subsequent leg involvement should be classified as a distinct clinicopathological variant of C-ALCL (“leg-type” involvement) and that they may require intense therapy.     

Microcirculatory changes in travelers to a tropical country

BACKGROUND: Travelers to tropical areas seem to be affected by nonhealing leg ulcers more frequently. One of the factors that can affect wound healing in a negative manner is leg edema. This study was performed to determine whether there is increased leg edema in travelers to tropical areas. METHOD: In this study, we measured the capillary filtration rate (CFR) of the lower leg by strain gauge plethysmography, as a measure of leg edema, on location in Surinam. Three groups were included: A, travelers in the first few weeks after arrival; B, travelers who had stayed in the tropics for a minimum of 2 months; C, native inhabitants. RESULTS: The mean CFR (mL/100 mL tissue/min) was significantly higher in group A than in groups B and C; the difference between groups B and C was not significant (group A 0.05 mL/100 mL tissue/min (standard deviation (SD), 0.03) vs. group B 0.02 mL/100 mL tissue/min (SD, 0.02), P = 0.01, and vs. group C 0.02 mL/100 mL tissue/min (SD, 0.02), P = 0.01). CONCLUSIONS: Travelers to tropical areas are affected by increased CFR in the first few weeks after arrival. A prolonged stay leads to the normalization of the CFR. Compression therapy is recommended for travelers to the tropics.     

Toxic Epidermal Necrolysis Possibly Linked to Hyperacute Graft-versus-Host Disease after Allogeneic Bone Marrow Transplantation

Toxic epidermal necrolysis (TEN) is a severe blistering skin disease of high mortality. TEN may occur after bone marrow transplantation (BMT). In such cases, TEN have been attributed to graft-versus-host disease (GVHD) or an adverse drug reaction. It is very difficult to distinguish the causes of TEN after BMT. We report a 21-year-old Japanese man who developed TEN eight days after BMT, evaluate the differential diagnosis of hyperacute GVHD and an adverse drug reaction, and deduce that hyperacute GVHD was the more likely pathogenesis of TEN in this patient.     

Kompressionstherapie des Ulcus cruris

Compression therapy is well-tried treatment with only few side effects for most patients with leg ulcers and/or edema. Despite the very long tradition in German-speaking countries and good evidence for compression therapy in different indications, recent scientific findings indicate that the current situation in Germany is unsatisfactory. Today, compression therapy can be performed with very different materials and systems. In addition to the traditional bandaging with Unna Boot, short-stretch, long-stretch, or multicomponent bandage systems, medical compression ulcer stockings are available. Other very effective but far less common alternatives are velcro wrap systems. When planning compression therapy, it is also important to consider donning devices with the patient. In addition to compression therapy, intermittent pneumatic compression therapy can be used. Through these various treatment options, it is now possible to develop an individually accepted, geared to the needs of the patients, and functional therapy strategy for nearly all patients with leg ulcers.