RESUMEN
Cyclophosphamide (CYC) has been a gold standard of treatment for severe progressive Systemic Sclerosis (SSc), especially in patients with concomitant interstitial lung disease (ILD). This approach was based on results of several interventional studies, including randomized control trials, which mainly addressed SSc-ILD as a primary end point and skin involvement as a second one. The use of CYC is time-limited due to significant adverse events. More recently, other immunosuppressive and biological agents showed efficacy but better safety profile in patients with SSc and SSc-ILD. With regards to other end-points, post-hoc analyses, systematic reviews and metalysis showed that CYC had limited influence on patients' quality of life, event-free survival and mortality. Comprehensive patient's stratification according to a molecular, cellular and phenotypic pattern may help in choosing of personalized medicine with more ambitious treatment effect and should be the future direction. According to the above available data and even if scientific evidence may be missing, experts' opinion has changed the attitude to CYC as an anchor drug in the management of severe SSc. Indeed, CYC has been pushed to the second and even third treatment option after mycophenolate mofetil, tocilizumab or rituximab. This position became obvious during debate on this topic at CORA meeting 2023.
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Enfermedades Pulmonares Intersticiales , Esclerodermia Difusa , Esclerodermia Sistémica , Humanos , Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/complicaciones , Calidad de Vida , Esclerodermia Difusa/inducido químicamente , Esclerodermia Difusa/complicaciones , Esclerodermia Difusa/tratamiento farmacológico , Esclerodermia Sistémica/complicacionesAsunto(s)
Esclerodermia Difusa , Esclerodermia Sistémica , Humanos , Esclerodermia Difusa/inducido químicamente , Esclerodermia Difusa/tratamiento farmacológico , Piel , Pirimidinas/efectos adversos , Piperidinas , Esclerodermia Sistémica/inducido químicamente , Esclerodermia Sistémica/tratamiento farmacológicoRESUMEN
INTRODUCTION/OBJECTIVES: Scleroderma is a rare complication in taxanes therapy. Although individual cases of taxanes-induced scleroderma have been reported, the clinical manifestation and treatment outcomes were reviewed and summarized rarely. This study reported a patient who developed diffuse scleroderma and possible scleroderma renal crisis after paclitaxel therapy for ureter cancer. METHOD: A PubMed literature review on published cases of taxanes-induced scleroderma up until April 2022 was included for analysis. RESULTS: The search identified 27 patients with adequate information for analysis. Of the 28 patients, including the one presented here, 22 were female. Peripheral edema was the most common symptom in all but one patient, and often accompanied by erythema in 11. Symptoms usually occurred in half of the patients within the 4th course of treatment. Skin lesions gradually progressed to skin fibrosis, and extended proximally. Internal organ involvements were uncommon. Antinuclear antibody tests were positive occasionally, but anti-Scl70 and anti-centromere usually were negative. Taxanes therapy was discontinued, continued and unavailable in 21, 3, and 4 patients, respectively. Corticosteroids for skin lesions with or without immunosuppressive drugs were given to 15 patients. Of 25 patients with available skin outcomes, 19 improved. There was no significant skin improvement between those who did or did not receive skin treatment (62.5% vs. 75.0%, p = 0.37). Skin usually improved after discontinuing taxanes. CONCLUSION: Taxanes-induced scleroderma is different from idiopathic scleroderma. Physicians should be aware of this condition in order to provide early diagnosis and apply appropriate management in order to avoid serious complications from severe skin sclerosis. Key Points ⢠Scleroderma is a rare but unique and serious complication of taxanes therapy ⢠Skin manifestations and distribution are similar to idiopathic scleroderma, but vascular phenomenon, internal organ involvement and scleroderma-associated auto-antibodies are presented rarely. Skin improvement usually occurs shortly after discontinuing taxanes ⢠The role of immunosuppressive therapy in treating taxanes-induced scleroderma is not clear.
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Lesión Renal Aguda , Esclerodermia Difusa , Esclerodermia Localizada , Esclerodermia Sistémica , Humanos , Femenino , Masculino , Paclitaxel/efectos adversos , Esclerodermia Difusa/inducido químicamente , Esclerodermia Difusa/complicaciones , Esclerodermia Difusa/tratamiento farmacológico , Taxoides/efectos adversos , Esclerodermia Localizada/inducido químicamente , Esclerodermia Localizada/tratamiento farmacológico , Esclerodermia Localizada/complicaciones , Esclerodermia Sistémica/inducido químicamente , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , Lesión Renal Aguda/complicaciones , Eritema/complicacionesAsunto(s)
Depresores del Apetito/efectos adversos , Sobrepeso/tratamiento farmacológico , Fentermina/efectos adversos , Esclerodermia Difusa/inducido químicamente , Adulto , Amlodipino/uso terapéutico , Depresores del Apetito/administración & dosificación , Biopsia , Esquema de Medicación , Quimioterapia Combinada , Femenino , Mano , Humanos , Ácido Micofenólico/uso terapéutico , Fentermina/administración & dosificación , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/tratamiento farmacológico , Esclerodermia Difusa/patología , Piel/patología , Factores de TiempoAsunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/efectos adversos , Esclerodermia Difusa/inducido químicamente , Esclerodermia Difusa/patología , Adulto , Biopsia con Aguja , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Mastectomía/métodos , Paclitaxel/uso terapéutico , Medición de Riesgo , Privación de TratamientoRESUMEN
Immune checkpoint inhibitors are approved for select cancer treatment and have shown survival benefit in patients with advanced melanoma. Adverse events, including immune-related adverse events, are common and potentially life-threatening. We describe cases of 2 patients with scleroderma (patient 1 had diffuse scleroderma, and patient 2 had limited scleroderma) that developed while they were receiving pembrolizumab therapy for metastatic melanoma. Prompt recognition and treatment of immune-related adverse events may improve tolerance to immune checkpoint inhibitors and contribute to an understanding of the manifesting autoimmune disease.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Esclerodermia Difusa/inducido químicamente , Esclerodermia Limitada/inducido químicamente , Anciano , Humanos , Inmunoterapia/métodos , Masculino , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Esclerodermia Difusa/patología , Esclerodermia Limitada/patologíaAsunto(s)
Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Docetaxel/efectos adversos , Matriz Extracelular/efectos de los fármacos , Esclerodermia Difusa/inducido químicamente , Piel/efectos de los fármacos , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Células Cultivadas , Quimioterapia Adyuvante/efectos adversos , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Fibrosis , Humanos , Persona de Mediana Edad , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/tratamiento farmacológico , Esclerodermia Difusa/metabolismo , Piel/metabolismo , Piel/patologíaRESUMEN
The term autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) or Shoenfeld's syndrome refers to a wide group of immune-mediated diseases triggered by external agents. Several substances, such as vaccine adjuvants, squalene and silicone implants, are implied in the pathogenesis of ASIA syndrome. Treatment and prognosis of this complex condition are not completely known due to lack of good quality evidence. After a brief introductory literature review on ASIA, we report here two cases of patients that developed rapidly progressive systemic sclerosis clinical features after multiple intramuscular local injections of a substance recommended by a non-medical professional called ADE. ADE is an oily vitamin complex for veterinary use, and it was used in these cases for cosmetic muscular definition and enhancement purpose. To our knowledge, this is the first paper to describe the relation between injections of ADE and the development of ASIA with severe systemic sclerosis phenotype. Further investigation is needed to better understand the pathophysiology and to provide the basis for the treatment of this condition.
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Adyuvantes Farmacéuticos/efectos adversos , Esclerodermia Difusa/inducido químicamente , Adyuvantes Farmacéuticos/administración & dosificación , Adulto , Humanos , Inyecciones Intramusculares , Masculino , Rituximab/uso terapéutico , Esclerodermia Difusa/tratamiento farmacológico , Esclerodermia Difusa/patología , Síndrome , Vitamina A/administración & dosificación , Vitamina D/administración & dosificación , Vitamina E/administración & dosificación , Vitaminas/administración & dosificaciónRESUMEN
OBJECTIVE: Systemic sclerosis (SSc) is a rare intractable disease with unmet medical need and fibrosis-related mortality. Absence of efficient treatments has prompted the development of novel therapeutic strategies, among which mesenchymal stem cells/stromal cells (MSCs) or progenitor stromal cells appear to be one of the most attractive options. The purpose of this study was to use the murine model of hypochlorite-induced SSc to investigate the systemic effects of MSCs on the main features of the diffuse form of the disease: skin and lung fibrosis, autoimmunity, and oxidative status. METHODS: We compared the effects of different doses of MSCs (2.5 × 10(5) , 5 × 10(5) , and 10(6) ) infused at different time points. Skin thickness was assessed during the experiment. At the time of euthanasia, biologic parameters were quantified in blood and tissues (by enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, assessment of collagen content). Assessments of histology and immunostaining were also performed. RESULTS: A lower expression of markers of fibrosis (Col1, Col3, Tgfb1, and aSma) was observed in both skin and lung following MSC infusion, which was consistent with histologic improvement and was inversely proportional to the injected dose. Importantly, sera from treated mice exhibited lower levels of anti-Scl-70 autoantibodies and enhanced antioxidant capacity, confirming the systemic effect of MSCs. Of interest, MSC administration was efficient in both the preventive and the curative approach. We further provide evidence that MSCs exerted an antifibrotic role by normalizing extracellular matrix remodeling parameters as well as reducing proinflammatory cytokine levels and increasing antioxidant defenses. CONCLUSION: The results of this study demonstrate the beneficial and systemic effects of MSC administration in the HOCl murine model of diffuse SSc, which is a promising finding from a clinical perspective.
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Autoanticuerpos/inmunología , Pulmón/patología , Trasplante de Células Madre Mesenquimatosas , Fibrosis Pulmonar/terapia , Esclerodermia Difusa/terapia , Piel/patología , Actinas/genética , Animales , Colágeno Tipo I/genética , Colágeno Tipo III/genética , ADN-Topoisomerasas de Tipo I/inmunología , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Fibrosis , Ácido Hipocloroso/toxicidad , Pulmón/inmunología , Pulmón/metabolismo , Ratones , Oxidantes/toxicidad , Estrés Oxidativo/inmunología , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Esclerodermia Difusa/inducido químicamente , Esclerodermia Difusa/inmunología , Esclerodermia Difusa/patología , Piel/inmunología , Piel/metabolismo , Transcriptoma , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
BACKGROUND: Occupational exposure is reported as playing a substantial causative role in systemic sclerosis (SSc). OBJECTIVE: We sought to compare the characteristics of SSc in patients with and without occupational exposure to crystalline silica/solvents. METHODS: In all, 142 patients with SSc were enrolled in this prospective study. An expert committee performed blind evaluation of occupational exposure to crystalline silica/solvents. RESULTS: Patients exposed to crystalline silica more often exhibited: diffuse cutaneous SSc (P = .02), digital ulcers (P = .05), interstitial lung disease (P = .0004), myocardial dysfunction (P = .006), and cancer (P = .06). Patients exposed to solvents more frequently developed: diffuse cutaneous SSc (P = .001), digital ulcers (P = .01), interstitial lung disease (P = .02), myocardial dysfunction (P = .04), and cancer (P = .003); in addition, these patients were more frequently anti-Scl 70 positive and anticentromere negative. Under multivariate analysis, significant factors for SSc associated with exposure to silica/solvents were: male gender (odds ratio 19.31, 95% confidence interval 15.34-69.86), cancer (odds ratio 5.97, 95% confidence interval 1.55-23.01), and digital ulcers (odds ratio 2.42, 95% confidence interval 1.05-5.56). LIMITATIONS: The cohort originated from a single geographic region. CONCLUSION: Occupational exposure to crystalline silica/solvents is correlated with more severe forms of SSc characterized by: diffuse cutaneous involvement, interstitial lung disease, general microangiopathy (digital ulcers and myocardial dysfunction), and association with cancer. Occupational exposure should be systematically checked in all patients with SSc, as exposed patients seem to develop more severe forms of SSc.
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Dermatitis Profesional/etiología , Exposición Profesional/efectos adversos , Esclerodermia Sistémica/inducido químicamente , Dióxido de Silicio/efectos adversos , Solventes/efectos adversos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Esclerodermia Difusa/inducido químicamente , Esclerodermia Sistémica/diagnósticoRESUMEN
OBJECTIVES: Epigenetic modifications such as DNA methylation and histone acetylation have been implicated in the pathogenesis of systemic sclerosis. However, histone methylation has not been investigated so far. We therefore aimed to evaluate the role of the trimethylation of histone H3 on lysine 27 (H3K27me3) on fibroblast activation and fibrosis. METHODS: H3K27me3 was inhibited by 3-deazaneplanocin A (DZNep) in cultured fibroblasts and in two murine models of dermal fibrosis. Fibrosis was analysed by assessment of the dermal thickening, determination of the hydroxyproline content and by quantification of the numbers of myofibroblasts. The expression of fos-related antigen 2 (fra-2) was assessed by real-time PCR, western blot and immunohistochemistry and modulated by siRNA. RESULTS: Inhibition of H3K27me3 stimulated the release of collagen in cultured fibroblasts in a time and dose-dependent manner. Treatment with DZNep exacerbated fibrosis induced by bleomycin or by overexpression of a constitutively active transforming growth factor ß receptor type I. Moreover, treatment with DZNep alone was sufficient to induce fibrosis. Inhibition of H3K27me3 induced the expression of the profibrotic transcription factor fra-2 in vitro and in vivo. Knockdown of fra-2 completely prevented the profibrotic effects of DZNep. CONCLUSIONS: These data demonstrate a novel role of H3 Lys27 histone methylation in fibrosis. In contrast to other epigenetic modifications such as DNA methylation and histone acetylation, H3 Lys27 histone methylation acts as a negative regulator of fibroblast activation in vitro and in vivo by repressing the expression of fra-2.
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Fibroblastos/enzimología , Histonas/metabolismo , Histona Demetilasas con Dominio de Jumonji/metabolismo , Esclerodermia Difusa/metabolismo , Esclerodermia Difusa/patología , Adulto , Animales , Antibióticos Antineoplásicos/farmacología , Bleomicina/farmacología , Células Cultivadas , Colágeno/metabolismo , Metilación de ADN/efectos de los fármacos , Metilación de ADN/fisiología , Dermis/patología , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Epigénesis Genética/efectos de los fármacos , Epigénesis Genética/fisiología , Fibroblastos/patología , Fibrosis/inducido químicamente , Fibrosis/metabolismo , Fibrosis/patología , Antígeno 2 Relacionado con Fos/metabolismo , Humanos , Histona Demetilasas con Dominio de Jumonji/antagonistas & inhibidores , Masculino , Ratones , Ratones Endogámicos DBA , Persona de Mediana Edad , Esclerodermia Difusa/inducido químicamente , Adulto JovenAsunto(s)
Antineoplásicos/efectos adversos , Síndrome Mano-Pie/etiología , Indoles/efectos adversos , Pirroles/efectos adversos , Anciano , Artritis Reumatoide/inducido químicamente , Carcinoma de Células Renales/tratamiento farmacológico , Femenino , Síndrome Mano-Pie/patología , Humanos , Neoplasias Renales/tratamiento farmacológico , Esclerodermia Difusa/inducido químicamente , SunitinibAsunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Transicionales/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Desoxicitidina/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Esclerodermia Difusa/inducido químicamente , Humanos , MasculinoRESUMEN
We report the first case of scleroderma-like skin sclerosis induced by docetaxel chemotherapy for prostate cancer in Japan. A 67-year-old man underwent radical prostatectomy for cT3aN0M0 prostate cancer in 2003. Thereafter PSA recurrence developed and antiandrogen deprivation therapy was used. However, we diagnosed this case as hormone refractory prostate cancer and began docetaxel chemotherapy in October 2008. There were no nonhematological adverse events through two courses of treatment. He presented to dermatology due to pain and swelling of both upper arms on the second day of the third course. However, when treated with a cooling method, swelling of the upper arms became worse and CPK rose to 1,921 IU/I on the eighth day. We administered a steroid ointment and an antibiotic due to suspicion of thrombophlebitis. Nevertheless, CPK rose to 2,791 IU/I and a skin biopsy was done. In consequence, scleroderma-like skin sclerosis induced by docetaxel chemotherapy was diagnosed. Swelling appeared in both lower limbs and the pain got worse on the 17th day. Therefore docetaxel chemotherapy was discontinued and prednisolone was increased to 30 mg/day, in addition to beginning codeine use for the pain. Thereafter, the painful sclerosis was ameliorated.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Esclerodermia Difusa/inducido químicamente , Taxoides/efectos adversos , Anciano , Docetaxel , Resistencia a Antineoplásicos , Humanos , Masculino , Prednisolona/administración & dosificación , Neoplasias de la Próstata/etiología , Esclerodermia Difusa/patología , Taxoides/administración & dosificaciónRESUMEN
BACKGROUND: Diffuse systemic sclerosis (DSS) is an autoimmune disease that is most often endogenous but which can also be induced by exogenous substances of occupational origin. PATIENTS AND METHODS: We report a case of DSS involving prolonged intermittent occupational exposure to solvents (trichloroethylene [TCE] and perchloroethylene [PCE]). The disease was rapidly fatal with cardiac arrest secondary to myocardial fibrosis. DISCUSSION: In the event of exposure to TCE/PCE, we suggest more systematic prevention and diagnosis of DSS.
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Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Esclerodermia Difusa/inducido químicamente , Tetracloroetileno/efectos adversos , Tricloroetileno/efectos adversos , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Tejido Adiposo/patología , Anabolizantes/efectos adversos , Calcinosis/inducido químicamente , Úlcera del Pie/inducido químicamente , Esclerodermia Difusa/inducido químicamente , Adulto , Calcinosis/complicaciones , Calcinosis/diagnóstico , Diagnóstico Diferencial , Fibrosis/inducido químicamente , Fibrosis/complicaciones , Fibrosis/diagnóstico , Úlcera del Pie/complicaciones , Úlcera del Pie/diagnóstico , Humanos , Masculino , Esclerodermia Difusa/complicaciones , Esclerodermia Difusa/diagnósticoRESUMEN
The name scleroderma is given to a spectrum of diseases which differ clinically and bear different prognostic risks. The origins of the various forms of the disease are unclear. A toxic influence has been suggested, particularly for the progressive systemic scleroderma. However, the imputability of the suspected chemicals often remains unsettled.
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Esclerodermia Sistémica/inducido químicamente , Dióxido de Silicio/efectos adversos , Autoanticuerpos/sangre , Biomarcadores/sangre , Diagnóstico Diferencial , Humanos , Hidrocarburos Aromáticos/efectos adversos , Pronóstico , Esclerodermia Difusa/inducido químicamente , Esclerodermia Localizada/inducido químicamente , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/patologíaRESUMEN
OBJECTIVE: Adenosine regulates inflammation and tissue repair, and adenosine A2A receptors promote wound healing by stimulating collagen matrix production. We therefore examined whether adenosine A2A receptors contribute to the pathogenesis of dermal fibrosis. METHODS: Collagen production by primary human dermal fibroblasts was analyzed by real-time polymerase chain reaction, 14C-proline incorporation, and Sircol assay. Intracellular signaling for dermal collagen production was investigated using inhibitors of MEK-1 and by demonstration of ERK phosphorylation. In vivo effects were studied in a bleomycin-induced dermal fibrosis model using adenosine A2A receptor-deficient wild-type littermate mice, C57BL/6 mice, and mice treated with adenosine A2A receptor antagonist. Morphometric features and levels of hydroxyproline were determined as measures of dermal fibrosis. RESULTS: Adenosine A2A receptor occupancy promoted collagen production by primary human dermal fibroblasts, which was blocked by adenosine A2A, but not A1 or A2B, receptor antagonism. Adenosine A2A receptor ligation stimulated ERK phosphorylation, and A2A receptor-mediated collagen production by dermal fibroblasts was blocked by MEK-1 inhibitors. Adenosine A2A receptor-deficient and A2A receptor antagonist-treated mice were protected from developing bleomycin-induced dermal fibrosis. CONCLUSION: These results demonstrate that adenosine A2A receptors play an active role in the pathogenesis of dermal fibrosis and suggest a novel therapeutic target in the treatment and prevention of dermal fibrosis in diseases such as scleroderma.
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Dermis/metabolismo , Fibroblastos/metabolismo , Fibrosis/metabolismo , Receptor de Adenosina A2A/metabolismo , Esclerodermia Difusa/metabolismo , Animales , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Dermis/efectos de los fármacos , Dermis/patología , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Fibrosis/patología , Fibrosis/prevención & control , Expresión Génica , Humanos , Hidroxiprolina/metabolismo , MAP Quinasa Quinasa 1/antagonistas & inhibidores , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , ARN Mensajero/metabolismo , Receptor de Adenosina A2A/deficiencia , Receptor de Adenosina A2A/genética , Esclerodermia Difusa/inducido químicamente , Esclerodermia Difusa/patología , Esclerodermia Difusa/prevención & control , Triazinas/uso terapéutico , Triazoles/uso terapéuticoRESUMEN
INTRODUCTION: Familial occurrence of progressive systemic sclerosis is unusual. The occurrence of conjugal scleroderma is exceptional. EXEGESIS: We report here a case of systemic sclerosis in a wife and husband who both developed the onset of illness within a 10-year period. Solvent exposure was noted. CONCLUSION: The etiology of systemic sclerosis remains unknown. Environmental factors may play role in its pathogenesis.
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Esclerodermia Difusa/fisiopatología , Anciano de 80 o más Años , Ecocardiografía , Femenino , Humanos , Hipertensión Pulmonar/complicaciones , Masculino , Esclerodermia Difusa/inducido químicamente , Esclerodermia Difusa/diagnóstico , Solventes/toxicidadRESUMEN
A scleroderma-like disease has recently been described in association with taxanes. We present the first case of diffuse scleroderma occurring in a woman treated with doxorubicin and cyclophosphamide for breast cancer. The clinical pattern of skin involvement and histological alterations were identical to those found in the classical form of scleroderma. Skin involvement progressed to affect 80% of total body area, and subsequently remained unchanged despite progression of the underlying cancer, making a paraneoplastic aetiology of the scleroderma unlikely. Specific chemotherapeutic agents might be directly responsible for the clinical manifestations and the parameters of progression. Analysis of all similar case reports defines the particular features and clinical course of this phenomenon.