Success treatment of post-irradiation morphoea with acitretin and narrowband UVB

Post-irradiation morphoea is a rare but under-recognised complication of radiotherapy treatment for breast cancer. Management of this condition is difficult, and many cases are recalcitrant to therapy. A 43-year-old woman with breast cancer received radiotherapy following a mastectomy and partial axillary lymph node dissection, shortly after which she developed a hot, tender, erythematous and indurated plaque at the mastectomy site. Subsequently the skin became retracted, depressed and hyperpigmented. The clinical features, along with histological findings, were consistent with post-irradiation morphoea. Treatment with narrowband ultraviolet B and acitretin 10 mg daily was commenced 5 years following radiotherapy. After 2 months of therapy the patient reported significant improvement in tenderness and range of left arm movement. Objectively the plaque was less indurated and softer to palpation. We propose that this treatment regimen is an option in the management of post-irradiation morphoea.     

Genital lichen sclerosus associated with morphoea or systemic sclerosis: clinical and HLA characteristics

Although patients with both morphoea and lichen sclerosus have been reported previously, in the majority of these reports the lichen sclerosus has been extragenital. We report nine patients in whom genital lichen sclerosus coexisted with scleroderma spectrum disorders including seven with morphoea, one with morphoea and lichen planus, and one with systemic sclerosis. The clinical features, associated autoimmune disease, autoantibodies and HLA type are reported. Antibodies to Borrelia burgdorferi were not detected in any of the patients. The coexistence of these diseases raises a number of intriguing questions about the relationship between them.     

UVA1 phototherapy is effective in darker skin: a review of 101 patients of Fitzpatrick skin types I-V

Background  Studies suggest ultraviolet (UV) A1 phototherapy is efficacious and safe in treating a variety of skin disorders. However, most reports evaluating the benefits of UVA1 phototherapy have been from Europe, focusing on a predominantly Caucasian population. Darker skin types have been evaluated only sparingly; none the less, it is widely held that these patients respond poorly to UVA1 phototherapy due to increased pigmentation.
Objectives  We aim to compare efficacy (clinical improvement scores) of UVA1 phototherapy among Fitzpatrick skin types.
Methods  A retrospective analysis of 101 patients receiving UVA1 treatment at the University of Texas Southwestern Medical Center in Dallas, TX was performed. Data on Fitzpatrick skin type and cumulative UVA1 doses were collected. Clinical improvement scores based on body surface area, erythema, induration, sclerosis, pigmentation, and symptoms of pain or pruritus were obtained.
Results  In the population studied, with morphoea and scleroderma being the most frequent diagnoses, improvement scores from UVA1 phototherapy and mean cumulative UVA1 doses were not significantly different among the Fitzpatrick skin types evaluated. Furthermore, little or no correlation was found between improvement score and skin type.
Conclusions  Data indicate skin pigmentation as graded by Fitzpatrick skin type does not significantly influence the efficacy of UVA1 phototherapy. Thus, UVA1 should be considered as a therapeutic option in more darkly pigmented patients.     

Thirteen-megahertz ultrasound probe: its role in diagnosing localized scleroderma

BACKGROUND: Ultrasound imaging has been shown to be useful for the evaluation of systemic and localized scleroderma (LS). However, its specificity and sensitivity have not been studied. OBJECTIVES: To define morphological ultrasound diagnostic criteria in LS and to test their sensitivity and specificity with a 13-MHz ultrasound probe. METHODS: Forty plaques in 26 consecutive patients with LS were examined and compared blindly with 17 control plaques in 16 patients with skin diseases where LS was in the differential diagnosis. Data were also compared with a normal control group. Five patients were re-evaluated 12-18 months after the first examination. RESULTS: Ultrasound examination disclosed a characteristic dense image resembling a flattened 'yo-yo'. Undulations of the dermis, disorganization, loss of thickness and thickened hyperechoic bands in the hypodermis, and the 'yo-yo' image had a high sensitivity and a high specificity for LS. A 92% sensitivity and a 100% specificity for LS were found when at least four of these five signs were present. CONCLUSIONS: Thirteen-megahertz ultrasound is a valuable tool for diagnosing LS. Morphological ultrasound diagnostic criteria had a high specificity and a high sensitivity.     

Localized scleroderma in breast cancer patients treated with supervoltage external beam radiation: Radiation port scleroderma

Background: An association between systemic scleroderma, radiation, and breast cancer has been recognized. However, localized scleroderma in the radiation port of breast cancer patients has been rarely described.Objective: Our purpose was to describe the concurrence of localized scleroderma, supervoltage radiation, and breast carcinoma.Methods: Patients were prospectively evaluated in a tertiary care cancer center, and the literature was reviewed.Results: We describe six patients with breast cancer in whom localized scleroderma developed within their radiation port.Conclusion: Radiation port localized scleroderma can be a sequela of supervoltage radiation therapy in patients with breast cancer. Recognition is important because localized scleroderma can clinically mimic recurrent breast carcinoma.     

Linear morphoea follows Blaschko's lines

Background  The aetiology of morphoea (or localized scleroderma) remains unknown. It has previously been suggested that lesions of linear morphoea may follow Blaschko's lines and thus reflect an embryological development. However, the distribution of linear morphoea has never been accurately evaluated.
Objectives  We aimed to identify common patterns of clinical presentation in children with linear morphoea and to establish whether linear morphoea follows the lines of Blaschko.
Methods  A retrospective chart review of 65 children with linear morphoea was performed. According to clinical photographs the skin lesions of these patients were plotted on to standardized head and body charts. With the aid of Adobe Illustrator a final figure was produced including an overlay of all individual lesions which was used for comparison with the published lines of Blaschko.
Results  Thirty-four (53%) patients had the en coup de sabre subtype, 27 (41%) presented with linear morphoea on the trunk and/or limbs and four (6%) children had a combination of the two. In 55 (85%) children the skin lesions were confined to one side of the body, showing no preference for either left or right side. On comparing the overlays of all body and head lesions with the original lines of Blaschko there was an excellent correlation.
Conclusions  Our data indicate that linear morphoea follows the lines of Blaschko. We hypothesize that in patients with linear morphoea susceptible cells are present in a mosaic state and that exposure to some trigger factor may result in the development of this condition.     

Morphoea in three siblings

Atrophoderma of Pasini and Pierini (APP) is an uncommon form of localized morphoea that occurs as superficial, hyperpigmented plaques distributed mainly on the trunk and proximal part of the limbs. There is little information about the influence of genetic and environmental factors on disease susceptibility and expression for localized scleroderma, although APP familial cases have been reported. We report three siblings without a family history of autoimmune disease presenting cutaneous lesions suggesting morphoea (APP variant).     

Taxane-induced scleroderma

We report five women who presented with scleroderma due to taxanes, mimicking systemic sclerosis. All five patients had received taxane chemotherapy for the treatment of metastatic breast cancer. Marked oedema began first, followed by skin sclerosis occurring mainly at the distal ends of the extremities 6-12 months after the administration of taxane in all patients. Skin biopsies showed full-layer dermal fibrosis with thickened collagen bundles, and perivascular monocytic cell infiltration. These cases resemble systemic sclerosis in terms of their clinical course and histological findings. However, clinical findings including Raynaud's phenomenon and pulmonary fibrosis as well as immunological abnormalities associated with systemic sclerosis were not detected in any of the patients. Although the mechanisms have not been clarified, it should be noted that taxane is causally involved in the formation of scleroderma-like skin conditions.     

Successful Treatment of Scleroderma with PUVA Therapy

PUVA therapy was carried out on four patients with scleroderma; three of them had cutaneous manifestations of progressive systemic sclerosis and one other exhibited generalized morphea. PUVA therapy was given with daily doses of 0.25 J/cm² or 0.4 J/cm² for 3–8 weeks, resulting in total doses between 3.5 J/cm² and 9.6 J/cm². All four patients responded well to this treatment; improvements of hand closure, skin sclerosis index, and flexion of fingers or knee joints were obtained. Thus, PUVA appeared to be beneficial for treating scleroderma.     

系统性硬皮病肢端型与弥漫型73例临床特点分析

目的探讨系统性硬皮病(SSc)肢端型与弥漫型的临床特点及差异。方法回顾性分析47例肢端型和26例弥漫型SSc患者的临床资料,并比较两型差异。结果肢端型∶弥漫型≈1.81∶1;指趾骨吸收/溃疡、关节畸形/固定、趾雷诺现象、ACA(+)等发生率肢端型高于弥漫型(P<0.05~0.01);关节炎、肌炎、间质性肺炎、二/三尖瓣返流、肾脏受损等弥漫型高于肢端型(P<0.05~0.01);2例分别死于心衰和尿毒症,均属弥漫型。结论两型除皮肤变硬部位不同外,肢端型SSc以指、趾骨吸收、溃疡、关节畸形、固定功能障碍为显著临床特点;弥漫型SSc则以关节炎、肌炎、肺、心脏受累为显著临床特点。心肾受损可能是SSc致死的主要因素。     

Expression analysis of multiple microRNAs in each patient with scleroderma

In this study, we compared expression pattern of multiple microRNAs in individual patient with scleroderma with that in normal subject. Serum levels of six microRNAs (miR‐7 g, miR‐21, miR‐29b, miR‐125, miR‐145 and miR‐206) were evaluated using real‐time PCR in 15 patients with scleroderma and 15 normal subjects. While levels of the six microRNAs were similar between the two groups, we found significant difference in the ranks between miRNAs in patients with scleroderma. Additionally, levels of let‐7 g and miR‐125b showed strong and significant correlation in normal subjects, but not in patients with scleroderma. Thus, miRNA expression pattern may be different in patients with scleroderma. We also found the combination of serum levels of miR‐206 and miR‐21 was more useful in distinguishing patients with scleroderma from normal subjects than either miR‐206 or miR‐21 alone. Our study is the first to demonstrate different expression profiles of multiple microRNAs in each patient with scleroderma and examine its clinical significance.     

Morphoea: a manifestation of infection with Borrelia species?

BACKGROUND: Morphoea or localized scleroderma is a cutaneous inflammatory disease with still unknown aetiology. Borrelia burgdorferi as causative agent has been discussed controversially. OBJECTIVES: To assess the evidence for infection with B. burgdorferi in patients with morphoea by focus-floating microscopy (FFM). METHODS: Using standard histological equipment, tissue sections stained with a polyclonal B. burgdorferi antibody were simultaneously scanned through in two planes: horizontally as in routine cytology, and vertically by focusing through the thickness of the section, i.e. FFM. Part of the material was also investigated with a Borrelia-specific polymerase chain reaction (PCR). RESULTS: One hundred and twenty-two cases of morphoea and 68 controls (58 negative and 10 positive by PCR) were investigated for the presence of Borrelia within tissue specimens. Using FFM Borrelia was detected in 84 cases (68.9%) of morphoea and in all positive controls, but was absent in all negative controls. Borrelia was significantly more frequent in early inflammatory-rich (75%) than late inflammatory-poor (53%) cases (P = 0.018). What seemed to be vital microorganisms were mostly found close to the active border, while degenerated forms were more common in fibrosclerotic parts. The presence of B lymphocytes determined by CD20 staining proved to be a good positive predictor of the microorganism (correlation 0.85, P < 0.001). Borrelia-specific DNA was detected in only one of 30 cases of morphoea analysed by PCR. CONCLUSIONS: FFM is a reliable and highly sensitive method to detect Borrelia in tissue sections. The frequent detection of this microorganism in morphoea points to a specific involvement of B. burgdorferi or other similar strains in the development of or as a trigger of this disease.     

Expression of insulin-like growth factor-I in lesional and non-lesional skin of patients with morphoea

Background  Morphoea (scleroderma) is a chronic disorder characterized by circumscribed sclerotic plaques with the hallmark of increased fibroblast activation and fibrosis. Through its effect on connective tissue cells and immune cells, insulin-like growth factor (IGF)-I has been found to play a role in some autoimmune connective tissue diseases and has been implicated in the pathogenesis of several fibrotic disorders.
Objectives  To evaluate the role of IGF-I in the pathogenesis of morphoea.
Methods  The study was carried out on 15 patients with morphoea and nine healthy controls. Two 5-mm punch skin biopsies were taken from every patient (one from lesional and one from non-lesional skin) and a single biopsy was taken from the normal skin of each control. A 10-mL blood sample was also taken from each patient and control. Quantitative detection of tissue and serum levels of IGF-I was done using an enzyme-linked immunosorbent assay technique.
Results  IGF-I in lesional skin was significantly higher than in non-lesional and control skin ( P  =   0·001 and P  =   0·021, respectively). Moreover, a significantly higher level of IGF-I was detected in patient serum when compared with control serum ( P  <   0·001). A direct significant correlation existed between lesional and non-lesional skin level ( r  =   0·618, P  =   0·014), and between lesional skin level and Rodnan score ( r  =   0·538, P  =   0·039).
Conclusions  Despite the small sample size, this study suggests that IGF-I plays an important role in the pathogenesis of fibrosis, characteristic of morphoea. Studies on a larger number of patients with morphoea as well as on patients with systemic sclerosis are recommended. Furthermore, therapeutic trials using IGF-I antagonist (octreotide) are highly recommended in patients with morphoea.     

Ciprofloxacin utility as antifibrotic in the skin of patients with scleroderma

Scleroderma is an autoimmune connective tissue disorder that is characterized by microvascular injury, excessive fibrosis of the skin, and distinctive visceral changes that can involve the lungs, heart, kidneys and gastrointestinal tract. To date, although several drugs have been used to reduce fibrosis in scleroderma, there exists no effective pharmacological treatment. To determine if oral ciprofloxacin reduces the severity of scleroderma, a controlled, double‐blind randomized clinical trial, with placebo, was conducted on 32 patients with diffuse and limited scleroderma, who received oral ciprofloxacin (250 mg) or placebo every 12 h. Skin induration and thickness of the patients were clinically evaluated using the modified Rodnan skin score at the beginning and once per month during 6 months of treatment with ciprofloxacin. To monitor progression of the disease, a monthly hematological exam and clinical evaluation was done to explore renal and hepatic function for each patient. Thirty patients completed the study; one from the treatment group was excluded when presenting a skin reaction and another from the placebo group abandoned the study due to an exacerbation of disease. At the sixth month of the study, the ciprofloxacin group of patients showed a diminution in the modified Rodnan skin score (58% vs 18%, P = 0.003), showing no significant alterations in the laboratory assays in either groups of patients. Our results suggest that oral administration of ciprofloxacin for 6 months reduces the severity of symptoms affecting the skin of patients with systemic scleroderma, and does so without important secondary effects.     

Lower limb linear morphoea in a pregnant woman with known Graves' disease and cytomegalovirus immunoglobulin M positivity

We report a case of linear morphoea in a 21‐year‐old woman with known Graves' disease who was also cytomegalovirus (CMV) IgM‐positive and in her early first trimester of pregnancy. The histopathology showed hyalinisation of the dermis with perivascular superficial and deep lymphocytic infiltrates extending into the septae of the subcutis and impinging on adjacent lobules; there was also fibrosis of the subcutis. Magnetic resonance imaging showed T2 high intensity of the subcutaneous tissue and intermuscular planes of the thigh and leg. It is well known that morphoea can follow pregnancy and thyroid disease and that CMV is postulated to contribute in some patients. This case highlights a combination of risk factors for this disease that have not been reported collectively in the literature to our knowledge.     

A case of linear scleroderma and myasthenia gravis

We report a case of a 28-year-old woman with myasthenia gravis who developed linear scleroderma seven years later. Myasthenia gravis and scleroderma are rarely found in direct association with each other; there are only five such reported cases, all of which were systemic scleroderma patients. Although localized and systemic scleroderma are distinct entities, autoimmunity is believed to be involved in the pathogenesis of both. Myasthenia gravis and scleroderma may occur coincidentally, but an autoimmune predisposition seems to be the more likely underlying cause, as evidenced by an increased incidence of autoantibodies and autoimmune diseases.     

复方泽桑汤联合胸腺肽 治疗系统性硬皮病的临床疗效观察

目的回顾性分析复方泽桑汤联合胸腺肽治疗系统性硬皮病66例的临床疗效。方法评估复方泽桑汤联合胸腺肽治疗系统性硬皮病66例半年后的疗效。结果痊愈18例(27.3%),显效24例(36.4%),好转20例(30.3%),无效4例(6.1%),有效率为63.64%(42/66)。结论复方泽桑汤联合胸腺肽治疗系统性硬皮病疗效显著。     

结节性硬皮病

报告1例结节性硬皮病,患者在诊断为系统性硬皮病4年后,胸、背部出现瘢痕疙瘩样皮损,根据病史和组织病理学改变诊断为结节性硬皮病。该型硬皮病多继发于系统性硬皮病,治疗困难。     

Autoantibodies in Scleroderma

Autoantibodies directed against nuclear, nucleolar, and a number of cytoplasmic components are described in the sera of scleroderma patients. Early studies of autoantibodies that relied on cryopreserved sections of rodent organ substrates showed that approximately 50% of scleroderma patients had anti-nuclear antibodies (ANA). More recent studies that have used tissue culture cell substrates have shown that up to 98% of scleroderma patients have a positive ANA. In all of these studies, the presence of different patterns of staining have suggested that scleroderma sera reacted with a variety of intracellular antigens. The use of molecular and immunochemical techniques has now shown that over 20 intracellular autoantigens are targets of autoantibodies in scleroderma sera. Clinical studies have shown that these autoantibodies are important diagnostic and prognostic markers in scleroderma. In the future, autoantibody testing may be used to monitor the patient's response to immunological therapies.     

硬皮病皮损中巨噬细胞游走抑制因子的表达

目的:检测巨噬细胞游走抑制因子在硬皮病中的表达.方法:免疫组化方法检测巨噬细胞游走抑制因子在20例硬皮病患者皮损中的表达,以10名正常人皮肤组织为对照.结果:硬皮病皮损中巨噬细胞游走抑制因子表达明显高于正常对照组.结论:巨噬细胞游走抑制因子表达增强可能与硬皮病的发病有关.