Scleroderma-like Changes Research Articles

BG02 A case of Werner syndrome: undiagnosed progeroid syndrome presenting as female pattern hair loss

Abstract A 27-year-old woman of Pakistani heritage with a background of type 2 diabetes, hypertension, hypothyroidism, infertility and Achilles tendinopathy was referred to the dermatology department for diffuse hair loss. She had greying of the scalp hair from the age of 20 years and, on examination, there were signs of hair fragility and thinning. Biopsies showed female pattern hair loss. Topical minoxidil 5% twice daily was advised. At the consultation, it was noted that her facial features included a thin nose with micrognathia. She had dental implants and had undergone cataract surgery at 19 years of age. Scleroderma-like changes were noted on the face and over the distal joints, alongside axillary freckling and excessive lentigines for her age and skin type. She was of short stature and low weight, with a body mass index (BMI) of 15.4 kg m–2. There was thenar and hypothenar wasting and loss of gluteal fat. Her parents were consanguineous (first cousins). One of her brothers, who had similar facial features, died aged 30 years from osteosarcoma. The patient and her partner had undergone two unsuccessful cycles of in vitro fertilization following 5 years of failure to conceive naturally. Medication consisted of atorvastatin, Calcichew, levothyroxine, lisinopril, metformin, pioglitazone and repaglinide. Routine bloods and hormone profile were normal. Despite her age, BMI and statin treatment, blood lipids were raised and a liver ultrasound showed fatty changes. The dermatology department queried Werner syndrome and referral to a tertiary lipodystrophy clinic was made. The lipodystrophy genetic panel was completed. Homozygous null mutation at the WRN locus was found confirming a diagnosis of Werner syndrome. Werner syndrome is an extremely rare autosomal recessive form of progeroid syndrome first described by Otto Werner in 1904. The hallmark sign is the striking disproportion between the patient’s age and appearance. WRN encodes the eponymous WRN protein, a member of the RecQ-like DNA helicase family. The prognosis is unfavourable, with a mean survival of 54 years. Primary causes of mortality are cardiovascular disease and malignancy, with melanoma, thyroid cancer, osteosarcoma and soft tissue sarcoma being the most common forms. There is currently no specific treatment. Management is close multidisciplinary monitoring and treatment of associated conditions. A 2010 study of the Werner syndrome mouse model found vitamin C supplementation to be beneficial (Massip L, Garand C, Paquet ER et al. Vitamin C restores healthy aging in a mouse model for Werner syndrome. FASEB J 2010; 24:158–72). As the condition results in excess damage on ultraviolet exposure and a high risk of melanoma, as well as nonmelanoma skin cancers, an annual dermatology skin check is required.

Scleroderma-like Disease Due to Diffuse Monosodium Urate Crystal Deposition.

Scleroderma-like disease is defined as fibrosis of the skin caused by certain chemicals, drugs, environmental factors, or metabolic abnormalities, which manifests as scleroderma-like changes.1,2 However, large deposits of urate crystals in the skin and subcutaneous fascial tissue causing scleroderma-like disease have not been reported in the literature.

31789 Scleroderma associated with immune checkpoint inhibitor durvalumab

As the use of immune checkpoint inhibitors (ICI) in cancer treatment regimens continues to rise, so has the incidence of immune-related cutaneous adverse events (irCAEs). Among irCAEs, ICI-induced scleroderma and systemic sclerosis (SSc) are rare and poorly understood. We present a case of progressive and debilitating scleroderma-like changes in a 78-year-old female being treated with durvalumab (anti-PD-L1) for squamous cell carcinoma of the lung. After 12 treatments, the patient started to develop painful skin thickening, fibrosis, and erosions of the hands, ankles, feet, and ankles that subsequently worsened after treatment completion. A full-thickness biopsy confirmed the diagnosis of fibrosing dermatitis. Laboratory values were significant for a positive homogenous ANA (1:320) and an elevated C-reactive protein. The patient’s scleroderma proceeded to involve most of her trunks, arms, and legs despite treatment with hydroxychloroquine, systemic corticosteroids, mycophenolate mofetil, intravenous immunoglobulin, and apremilast. There have been less than 10 cases of limited cutaneous and diffuse cutaneous sclerosis reported in the literature following treatment with anti-PD-1 agents. To our knowledge, this is the first case of scleroderma following anti-PD-L1 therapy. As in this patient, ICI-induced scleroderma can be recalcitrant and can significantly impact quality of life. Patients on ICIs should be carefully examined for scleroderma-like changes as early recognition and treatment initiation could reduce disease severity and lead to improved tolerance to ICIs.

SGK1, a Critical Regulator of Immune Modulation and Fibrosis and a Potential Therapeutic Target in Chronic Graft-Versus-Host Disease.

Patients with severe chronic graft-versus-host disease (cGVHD) always experience debilitating tissue injury and have poorer quality of life and shorter survival time. The early stage of cGVHD is characterized by inflammation, which eventually leads to extensive tissue fibrosis in various organs, such as skin and lung, eventually inducing scleroderma-like changes and bronchiolitis obliterans syndrome. Here we review the functions of serum/glucocorticoid regulated kinase 1 (SGK1), a hub molecule in multiple signal transduction pathways and cell phosphorylation cascades, which has important roles in cell proliferation and ion channel regulation, and its relevance in cGVHD. SGK1 phosphorylates the ubiquitin ligase, NEDD4, and induces Th cells to differentiate into Th17 and Th2 phenotypes, hinders Treg development, and promotes inflammatory fibrosis. Phosphorylation of NEDD4 by SGK1 also leads to up-regulation of the transcription factor SMAD2/3, thereby amplifying the fibrosis-promoting effect of TGF-β. SGK1 also up-regulates the inflammatory transcription factor, nuclear factor-κB (NF-κB), which in turn stimulates the expression of multiple inflammatory mediators, including connective tissue growth factor. Overexpression of SGK1 has been observed in various fibrotic diseases, including pulmonary fibrosis, diabetic renal fibrosis, liver cirrhosis, hypertensive cardiac fibrosis, peritoneal fibrosis, and Crohn’s disease. In addition, SGK1 inhibitors can attenuate, or even reverse, the effect of fibrosis, and may be used to treat inflammatory conditions and/or fibrotic diseases, such as cGVHD, in the future.

M295 EOSINOPHILIC FASCIITIS IN COMMON VARIABLE IMMUNODEFICIENCY WITH HYPEREOSINOPHILIA

Eosinophilic fasciitis is a rare disorder that presents with scleroderma-like changes of connective tissues. There have been two cases of common variable immunodeficiency (CVID) associated with eosinophilic fasciitis reported in Europe. We report the first case of CVID associated with eosinophilic fasciitis in the United States in the setting of hypereosinophilia.

Eosinophilic fasciitis in common variable immunodeficiency with hypereosinophilia

Eosinophilic fasciitis or Shulman disease is a rare disorder that presents with scleroderma-like changes of connective tissues accompanied by elevated erythrocyte sedimentation rate, hypergammaglobulinemia, and transient peripheral eosinophilia. 1 Mazori D.R. Femia A.N. Vleugels R.A. Eosinophilic fasciitis: an updated review on diagnosis and treatment. Curr Rheumatol Rep. 2017; 19: 74 Crossref PubMed Scopus (34) Google Scholar To date, there have been 2 cases of common variable immunodeficiency (CVID) associated with eosinophilic fasciitis reported in Europe. Here, we report the first case of CVID associated with eosinophilic fasciitis in the setting of hypereosinophilia in the United States.

Autoimmune/inflammatory syndrome induced by adjuvants

The development of autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is associated with the hyperergic reaction of the human immune system. The development of autoimmune inflammation is preceded by contact with internal or external trigger factors (adjuvants) of immune disorders. ASIA is associated with an individual genetic predisposition that is probably associated with the carriage of HLA-DRB1*01 or HLA-DRB4. The paper presents five possible options for the impact of adjuvants in the pathogenesis of autoimmune disorders. It gives diagnostic criteria for the syndrome, as well as its clinical, laboratory and morphological manifestations. Emphasis is laid on the importance of morphological changes in the diagnosis of autoimmune disorders. The spectrum of morphological changes in ASIA is extensive. The tissues show signs of immune inflammation, such as lymphohistiocytic infiltration, granulomatous inflammation, and scleroderma-like changes. The characteristic feature is the regression of clinical, laboratory, and morphological manifestations after adjuvant removal.

Reversal of CD8 T-Cell–Mediated Mucocutaneous Graft-Versus-Host-Like Disease by the JAK Inhibitor Tofacitinib

The utility of allogeneic hematopoietic stem cell transplantation is limited by graft-versus-host disease (GVHD), a significant cause of morbidity and mortality. Patients with GVHD exhibit cutaneous manifestations with histological features of interface dermatitis followed by scleroderma-like changes. JAK inhibitors represent a class of immunomodulatory drugs that inhibit signaling by multiple cytokines. Herein we report the effects of tofacitinib in a murine model of GVHD. Oral administration of tofacitinib prevented GVHD-like disease manifested by weight loss and mucocutaneous lesions. More importantly, tofacitinib was also effective in reversing established disease. Tofacitinib diminished the expansion and activation of murine CD8 T cells in this model, and had similar effects on IL-2-stimulated human CD8 T cells. Tofacitinib also inhibited the expression of IFN-γ-inducible chemoattractants by keratinocytes, and IFN-γ-inducible cell death of keratinocytes. Tofacitinib may be an effective drug for treatment against CD8 T-cell–mediated mucocutaneous diseases in patients with GVHD.

Ocular manifestations of graft-versus-host disease

Allogeneic hematopoietic stem cell transplantation (HSCT) has evolved over the past two decades to become the standard of care for hematologic and lymphoid malignancies. Major ocular complications after allogeneic HSCT have been increasing in number and severity. Graft-versus-host disease (GVHD) remains a major cause of ocular morbidity after allogeneic HSCT. The main objective of this review is to elucidate the ocular complications in patients developing GVHD following HSCT.Ocular complications secondary to GVHD are common and include dry eye syndrome, acquisition of ocular allergy from donors with allergic disorders. Eyelid changes may occur in GVHD leading to scleroderma-like changes. Patients may develop poliosis, madarosis, vitiligo, lagophthalmos, and entropion. The cornea may show filamentary keratitis, superficial punctate keratitis, corneal ulcers, and peripheral corneal melting which may lead to perforation in severe cases. Scleritis may also occur which can be anterior or posterior. Keratoconjunctivis sicca appears to be the most common presentation of GVHD. The lacrimal glands may be involved with mononuclear cell infiltration of both the major and accessory lacrimal glands and decrease in tear production.Severe dry eye syndrome in patients with GVHD may develop conjunctival scarring, keratinization, and cicatrization of the conjunctiva.Therapy of GVHD includes systemic immunosuppression and local therapy. Surgical treatment in refractory cases includes surgical intervention to improve the manifestation of GVHD of the eye. This may include tarsorrhapy, prose lenses, punctal occlusions and corneal transplantation.

Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) syndrome is associated with severe chronic inflammation and cardiomyopathy, and represents a new monogenic autoinflammatory syndrome

Mutations in SLC29A3 lead to pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) and H syndromes, familial Rosai-Dorfman disease, and histiocytosis-lymphadenopathy plus syndrome. We report a new association of PHID syndrome with severe systemic inflammation, scleroderma-like changes, and cardiomyopathy. A 12-year-old girl with PHID syndrome presented with shortness of breath, hepatosplenomegaly, and raised erythrocyte sedimentation rate and C-reactive protein. An echocardiogram showed biventricular myocardial hypertrophy, and cardiac magnetic resonance imaging showed circumferential late gadolinium enhancement of the myocardium. No systemic amyloid deposits were observed on a whole-body serum amyloid P scintigraphy scan. Abdominal ultrasound revealed intra-abdominal fat surrounding the solid organs, suggesting a possibility of evolving lipodystrophy with visceral adiposity. PHID syndrome is a novel monogenic autoinflammatory syndrome (AIS) associated with severe elevation of serum amyloid. Lipodystrophy, cutaneous sclerodermatous changes, and cardiomyopathy were also present in this case. In contrast to other AIS, blockade of interleukin-1 and tumor necrosis-α was ineffective.

Fibrotic and Sclerotic Manifestations of Chronic Graft-versus-Host Disease

Chronic graft versus host disease (cGVHD) is a common cause of morbidity and mortality following allogeneic stem cell transplant (HCT), with approximately 50-60% of long-term HCT survivors developing one or more manifestations of the disorder. While acute GVHD is typically limited to skin, liver and gastrointestinal involvement, virtually every organ is at risk for the development of cGVHD. Though the pathophysiology of cGVHD remains poorly understood, some of the most severe organ manifestations are linked by end organ fibrosis. In particular, fibrotic cutaneous and bronchiolar changes, resulting in scleroderma-like changes and bronchiolitis obliterans syndrome (BOS), respectively, are two of the most devastating outcomes for these patients. Both sclerotic GVHD (ScGVHD) and BOS have been reported in 5 to 15% of patients with cGVHD (1, 2)ENREF 1. Unfortunately, standard treatment for cGVHD has not changed significantly in the past 30 years, and relies heavily on the use of agents that reduce the activity of alloreactive T-cells. Many of the manifestations of cGVHD however, share clinical characteristics seen in non-transplant conditions, including systemic sclerosis or pulmonary fibrosis. Thus, understanding the pathophysiology underlying these related conditions may help identify potential mechanisms and ultimately new therapeutic options for patients with cGVHD. Tyrosine kinase inhibitors (TKIs) have been shown to inhibit two different profibrotic pathways (transforming growth factor β [TGF-β] and platelet-derived growth factor [PDGF]) in various mouse models of fibrotic disease, and offer a possible novel treatment approach for cGVHD patients suffering from severe sclerosis (3). Likewise, overexpression of tumor necrosis factor (TNF)-α has been shown to induce fibrogenesis in experimental hepatocellular disease (4), and has been linked with human scleroderma-associated interstitial pulmonary fibrosis (5) and profibrotic responses in human osteoarthritic hip joint fibroblasts (6). The use of TNF antagonists has been examined in some clinical situations associated with fibrosis (7, 8), suggesting they may also be of some benefit to patients with cGVHD; however, this must first be prospectively tested.

Coexistence of systemic sclerosis, scleroderma-like syndromes and neoplastic diseases

Coexistence of rheumatic and neoplastic diseases may take different forms. Rheumatic paraneoplastic syndromes, including systemic sclerosis, scleroderma-like changes and Raynaud's phenomenon are induced by substances secreted by neoplastic cells and immunological disturbances connected are associated with malignancy. They may precede the clinical manifestation of neoplasm, occur simultaneously or after its diagnosis. In turn, chronic course of rheumatic diseases (Sjögren's syndrome, systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis) by immunologic stimulation may promote carcinogenesis. Genetic, environmental factors (viruses, chemical substances, radiation) and alterations of immunological surveillance may be the cause of both rheumatic and paraneoplastic disorders. Anticancer therapy may cause rheumatic diseases and immunosuppressive agents used in patients with rheumatic syndromes may have carcinogenic effect. Patients with long-standing or atypical course of rheumatic disorders, positive family or personal history of neoplastic disease, positive cancer markers, monoclonal antibodies or presence of other paraneoplastic syndromes should be diagnosed as possibly having occult neoplasm. In this paper we reviewed available literature on coexistence of rheumatic processes and malignancies to attract particular attention to practical aspects of this vital issue.

Preemptive HMG-CoA Reductase Inhibition Significantly Attenuates a Murine Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease (cGVHD) is a serious and increasingly common complication of allogeneic stem cell transplantation. Treatment of cGVHD remains a large challenge. Even though cGVHD differs among patients, the clinical complications of cGVHD often include fibrosis and scleroderma-like changes. A murine sclerodermatous graft-versus-host disease (Scl GVHD) model sharing critical characteristics with human cGVHD is characterized by skin thickening and lung fibrosis. Statins, 3-hydroxy-3-methyl-CoA (HMG-CoA) reductase inhibitors which are a class of cholesterol lowering drugs decreasing mortality from cardiovascular disease and stroke, have strong immunomodulatory effects on antigen-presenting cells and T cells interfering with synthesis of L-mevalonate and its downstream isoprenoid metabolites. It has been demonstrated that some statins inhibit the production of proinflammatory cytokines and improved chronic inflammatory disorders. We used B10.D2 → BALB/c model of cGVHD, which differ at minor histocompatibility loci, to address the therapeutic effect of statins on the development of cGVHD. Lethally irradiated (700 cGy) BALB/c mice were transplanted with either B10.D2 (allogeneic) or BALB/c (syngeneic) bone marrow (1.5 × 106) and spleen cells (3 × 106) to generate Scl GVHD. We have noted skin thickening as early as day 14, however 28 days was usually required to observe significant skin thickening in allogeneic recipients with Scl GVHD. The skin thickenings were still lingering on but weaken as late as 56 days post-alloSCT, whereas the loss of normal lacy alveolar pattern of lungs remained constant up to that time. Syngeneic recipients did not show any significant changes in each organ. In vivo treatment of pravastatin (30 mg/kg/day, intraperitoneally) for 10 days early after transplant led to greater suppression of the incidence and severity of clinical skin cGVHD compared with allogeneic controls injected with diluent. The occurrence of clinical cutaneous GVHD was significantly slower in onset in the recipients of pravastatin treatment than it in the control animals (36 days vs. 25 days, respectively, P<0.05) Blinded pathologic scoring of skin disease on day 28 confirmed the clinical result. Skin from pravastatin recipients had an average pathology score of 2.5 ± 0.3 compared with 6.9 ± 0.7 for the allogeneic controls (P<0.01). To qualify the cells infiltrating skin or lungs in early Scl GVHD, we examined the number of CD11b+ or CD3+ cells isolated from each organ of the animals with Scl GVHD with or without pravastatin treatment on day 14, 28 and 56 post-alloSCT. Compared with the allogeneic controls with diluent treatment, the injection of pravastatin significantly reduced the number of cells infiltrating each organ on day 14; for bronchoalveolar lavage fluid 3.2 ± 0.3 ×104 vs. 2.2 ± 0.3 ×104 (P<0.05, CD11b+) and 1.3 ± 0.1 ×104 vs. 0.33 ± 0.1 ×104 (P<0.05, CD3+), for skin 56 ± 4.3 ×104 vs. 10 ± 2.3 ×104 (P<0.01, CD11b+) and 12 ± 3.1 ×104 vs. 3 ± 1.8 ×104 (P<0.01, CD3+). On days 28 and 56, the infiltrating cells were also significantly reduced in the animals treated with pravastatin (data not shown). To test whether statins might produce an effect on attracting these monocytes to skin or lungs by influencing the chemokine expression, we performed semiquantitative RT-PCR analyses and ELISA on day 14 to examine the expression of MCP-1 and RANTES in skin and lungs from Scl GVHD animals treated by either pravastatin or the diluent. MCP-1 and RANTES mRNA levels as well as protein concentrations from each organ were significantly reduced in recipients treated with pravastatins compared to the allogeneic controls. In conclusion, preemptive HMG CoA reductase inhibition prevented murine Scl GVHD by effectively blocking the influx of monocytes into target organs and by down-regulating the expression of MCP-1 and RANTES, thereby reducing new collagen synthesis. The Scl GVHD model is valuable for testing the effect of statins on early fibrosing diseases, and chemokines may be the potential targets in cGVHD protection effect of statins.

Unilateral limited scleroderma‐like changes following formation of an arteriovenous fistula

A 55-year-old man presented with a 1-year history of progressive skin thickening involving the right hand associated with Raynaud's phenomenon, sclerodactyly and painful cutaneous ulcers. An arteriovenous fistula for haemodialysis had been formed on the same arm 2 years previously. There were no symptoms or signs of systemic sclerosis or involvement of the contralateral arm. The limb was clinically ischaemic, attributed to a vascular steal phenomenon from the arteriovenous fistula, superimposed on occlusive arterial disease. A revascularization procedure was performed, which resulted in substantial improvement in the sclerodactyly, Raynaud's phenomenon and hand function. Tissue hypoxia is believed to be a contributing factor in the pathogenesis of scleroderma, and this case demonstrates scleroderma-like changes in the setting of limb ischaemia.

Hand-Foot Syndrome with Scleroderma-like Change Induced by the Oral Capecitabine: A Case Report

Hand-foot syndrome (HFS) is a well-known adverse event associated with capecitabine, a prodrug of 5-Fluorouracil (5-FU). HFS manifests as acral erythema, with swelling and dysesthesia of the palms and plantar aspects of the feet, which in the absence of dosage reduction or drug cessation, progresses to moist desquamation and ulceration, resulting in serious infections and loss of function. We report a case of HFS, with scleroderma-like changes, apparently induced by capecitabine. In our case, capecitabine, given in the recommended dosage was observed to lead to hyperpigmentation of the palms and soles, followed by a distinct keratoderma-like thickening unfamiliar to usual cases of HFS. This case may provide important clues for revising the definition of HFS, and allow the formation of effective preventive strategies for this side effect of chemotherapy.

1052 POSTER Interleukin-6 levels in thyroid cancer and nodular goitre

Paclitaxel is a recent antineoplastic agent that belongs to the taxane family. Its activity has been demonstrated in advanced and refractory ovarian, breast, lung, and head and neck cancer. Adverse cutaneous reactions to paclitaxel have been reported, namely bullous fixed drug eruption, onycholysis, acral erythema, erythema multiforme, and pustular eruption. We report the first case of scleroderma-like changes after paclitaxel administration. A 63-year-old patient presented with an edematous and infiltrated erythema of the head, neck, axillae, and left hand 10 days after administration of paclitaxel and paraplatin for primitive peritoneal cancer. Cutaneous lesions improved after a change from paclitaxel to cyclophosphamide. Cutaneous lesions recurred 3 months later, after reintroduction of paclitaxel, and progressively evolved to cutaneous sclerosis. Skin biopsy showed a dermal fibrosis. Biologic tests revealed no autoimmunity. Scleroderma-like lesions of this patient were reminiscent of previously reported cases that occurred after administration of docetaxel, which also belongs to the taxan family. Thus, scleroderma-like syndromes seem to represent a unique cutaneous adverse event caused by taxanes. (J Am Acad Dermatol 2003;48:279-81.)

Methysergide-induced scleroderma-like changes of the legs

Conflicts of interest: none declared. Sir, Methysergide is a semisynthetic ergot alkaloid ergometrine derivative, acting as a serotonin receptor antagonist, used in migraine prophylaxis. Common reported side‐effects include cardiac and arterial vasospastic symptoms and systemic fibrosis, mainly retroperitoneal. We describe the first case, to our knowledge, of methysergide‐associated scleroderma‐like changes of the legs. A 63‐year‐old woman presented with a 2‐month history of inflammatory oedema of the legs and feet. Her medical history included: (i) migraine treated with methysergide 1·65 mg daily, which she had taken continuously for more than 10 years; (ii) depression treated with lorazepam 5 mg daily for 5 years; (iii) breast carcinoma treated 3 years previously by tumorectomy, lymphadenectomy, chemotherapy and radiotherapy; since then, she had been taking tamoxifen 20 mg daily and had so far remained in remission; (iv) gastritis treated with esomeprazole 20 mg daily for 2 years; and (v) hypercholesterolaemia treated with pravastatin 20 mg daily for 2 years.

Scleroderma-like changes in cutaneous eruption of rhabdomyolysis

To the Editor: A 66-year-old man presented with peculiar skin lesions on the right side of his face, chest wall, and scrotum of 2 days' duration. He had been a chronic alcohol abuser for the past 40 years. Three days before admission, he went mountain hiking, had an alcoholic binge, and slept in a right lateral decubitus position. The next morning, he awoke to find the skin lesions and admitted himself to the emergency department. He had been taking diltiazem and nitrate for stable angina. Physical examination revealed well-demarcated, erythematous, swollen plaques on the right side of the cheek, neck, chest wall, arm, and scrotum.

Gemcitabine-associated scleroderma-like changes of the lower extremities

Gemcitabine is a nucleosid analog approved for use in the treatment of metastatic urothelial carcinoma of the bladder. We describe an unusual case of scleroderma-like changes of the lower extremities after treatment by gemcitabine for metastatic carcinoma of the bladder. The patient developed initial inflammatory edema (3 kg) restricted to the lower extremities and subsequent scleroderma-like changes after 2 cycles of gemcitabine. Cutaneous biopsy specimen revealed diffuse sclerosis without involvment of the fascia or muscle. Discontinuation of gemcitabine resulted in dramatic removal of the edema, softening of the skin, and partial reversibility of the fibrotic process. This is the first case report of a scleroderma-like reaction associated with gemcitabine. This antineoplastic agent must be added to the very limited number of cytostatic agents capable of giving rise to scleroderma-like features.

Scleroderma-like cutaneous lesions induced by paclitaxel: A case study

Paclitaxel is a recent antineoplastic agent that belongs to the taxane family. Its activity has been demonstrated in advanced and refractory ovarian, breast, lung, and head and neck cancer. Adverse cutaneous reactions to paclitaxel have been reported, namely bullous fixed drug eruption, onycholysis, acral erythema, erythema multiforme, and pustular eruption. We report the first case of scleroderma-like changes after paclitaxel administration. A 63-year-old patient presented with an edematous and infiltrated erythema of the head, neck, axillae, and left hand 10 days after administration of paclitaxel and paraplatin for primitive peritoneal cancer. Cutaneous lesions improved after a change from paclitaxel to cyclophosphamide. Cutaneous lesions recurred 3 months later, after reintroduction of paclitaxel, and progressively evolved to cutaneous sclerosis. Skin biopsy showed a dermal fibrosis. Biologic tests revealed no autoimmunity. Scleroderma-like lesions of this patient were reminiscent of previously reported cases that occurred after administration of docetaxel, which also belongs to the taxan family. Thus, scleroderma-like syndromes seem to represent a unique cutaneous adverse event caused by taxanes. (J Am Acad Dermatol 2003;48:279-81.)