Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A link between systemic sclerosis (SSc) and malignancy is suggested by epidemiological evidence, but the underlying mechanism connecting both diseases has been a source of ongoing controversy. Here, we describe the first case of paraneoplastic SSc secondary to a primarily diagnosed melanoma. Two months after diagnosis of metastatic melanoma, a 40-year-old female presented with high serum titers of antinuclear antibodies (ANA), but no symptoms of autoimmune disease. Five months later, the onset of Raynaud's phenomenon together with highly positive Jo-1 antibodies was observed. The following clinical course of scleroderma was correlated to melanoma remission and progression. Finally, the patient developed severe pulmonary fibrosis, massive pleural effusion, severe thoracic scleroderma and necrosis of the fingertips, simultaneously with a progression of melanoma to disseminated lymph node metastases and a small brain metastasis. This rare case of SSc concurrent with melanoma suggests that besides other possible mechanisms, paraneoplastic etiology can be responsible for the association between SSc and cancer.
Eur J Dermatol
PMID:Jo-1 positive paraneoplastic systemic sclerosis in a patient with metastatic melanoma. 1693 4

Members of two generations of a South African family have a unique syndrome comprising poikiloderma, tendon contractures and progressive pulmonary fibrosis. The condition is clinically important as the skin changes, which involve the face, have considerable cosmetic impact, while lung involvement is potentially lethal in adulthood. Skin manifestations which facilitate diagnosis include facial telangiectasia, mottled hypo- and hyperpigmentation, papules and epidermal atrophy. The scalp, facial and body hair are fine and scanty. The tendon contractures lead to progressive digital flexion deformities and abnormalities of the ankles and feet, with disturbance of gait. Pulmonary involvement manifests as progressive dyspnoea. Pedigree data are compatible with an autosomal dominant mode of transmission. Poikiloderma of Weary is characterized by linear sclerotic and fibrous bands and not tendon contractures and is not associated with potentially lethal pulmonary fibrosis. Rather than name this disorder a variant of Weary syndrome, it might be prudent to use as an umbrella title one composed by Weary himself: 'hereditary sclerosing poikiloderma' (HSP), under which variants such as HSP Weary type, HSP with cardiac involvement (aortic stenosis described as inconsistently associated with Weary syndrome) and HSP with tendon/pulmonary involvement (current family) may be classified. The manifestations in this family differ from other poikilodermata and, to the best of our knowledge, have not been previously documented.
Br J Dermatol 2006 Nov
PMID:Poikiloderma, tendon contracture and pulmonary fibrosis: a new autosomal dominant syndrome? 1703 42

The pale ear (ep) mouse strain is a model for the Hermansky-Pudlak syndrome type 1 (HPS-1), an autosomal recessive disorder causing pigmentary dilution, visual disturbances, bleeding diatheses, pulmonary fibrosis, and granulomatous colitis. The ep mice have a coat color very similar to the black-colored parental strain, C57BL/6. However, the ears and tails of ep mice are significantly hypopigmented compared with the control animals, suggesting that the gene mutation in ep mice reveals a differential regulation of melanocyte function in dorsal back skin melanocytes versus tail or ear skin. In this study, we analyzed the mutant phenotype in detail and determined that in the tail, the defective gene causes delayed onset of interfollicular epidermal melanocyte tyrosinase activity, decreased numbers of melanocytes in the interfollicular epidermis and dermis, and severe immaturity of tail epidermal melanosomes, findings not observed in dorsal back follicular melanocytes. These results highlight differences between follicular and interfollicular melanocyte biology and demonstrate that defects in the ep protein not only affect melanosome biogenesis, but also play a developmental role in determining interfollicular epidermal and dermal melanocyte function. The implications of these findings for the mechanisms governing physiologic variation in human pigmentation and for the pathogenesis of vitiligo are discussed.
J Invest Dermatol 2007 Feb
PMID:Hermansky-Pudlak HPS1/pale ear gene regulates epidermal and dermal melanocyte development. 1706 83

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.
Br J Dermatol 2007 Feb
PMID:Taxane-induced scleroderma. 1722 79

Graft-versus-host disease (GvHD) is a common and often serious complication of hematopoietic stem cell transplantation. There are two major forms of GvHD: an acute form which develops in the first 100 days after HSCT, and a chronic form which develops later. Chronic GvHD is a multiorgan syndrome with many features of autoimmune diseases, such as sclerodermatous skin changes, cholestasis, pulmonary fibrosis, xerostomia, oral ulcerations, myositis and fasciitis. Unlike acute GvHD which is characterized by acute alloreactivity,the etiology of chronic GvHD is controversial and is believed to be either an extension of acute GvHD and/or a result of dysfunctional immune reconstitution with generation of autoantibodies and autoreactive T-cell clones. GvHD is usually treated with corticosteroids and other immunosuppressants which do not always succeed in arresting its evolution. Extracorporeal photochemotherapy has been used in patients with both acute and chronic GvHD.
J Dtsch Dermatol Ges 2008 Jun
PMID:Extracorporeal photopheresis in graft-versus-host disease. 1817 13

It is unclear whether any clinical and laboratory features are associated with pulmonary fibrosis (PF) in systemic sclerosis (SSc). We assessed these features using a database of 29 patients with SSc and anti-topoisomerase I antibodies and 68 patients with SSc and anticentromere antibody (ACA). Clinical features were not associated with the incidence of PF in patients with SSc and anti-topoisomerase I antibodies, although severe skin sclerosis was correlated with the presence of PF in patients with ACA. Serum IgG levels were often raised in patients with SSc and PF. Serum IgG levels in patients with PF were significantly higher than those in patients without PF, and were negatively correlated with percentage vital capacity and percentage diffusing capacity of the lung for carbon monoxide. In addition, serum IgG levels were correlated with serum interleukin-6. Thus, serum IgG levels are associated with PF in patients with SSc and anti-topoisomerase I antibodies and in patients with SSc and ACA.
Clin Exp Dermatol 2008 May
PMID:Elevation of IgG levels is a serological indicator for pulmonary fibrosis in systemic sclerosis with anti-topoisomerase I antibodies and those with anticentromere antibody. 1831 58

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis and vascular changes in the skin and internal organs with autoimmune background. It has been suggested that oxidative stress plays an important role in the development of SSc. To determine the prevalence and clinical correlation of autoantibody to methionine sulfoxide reductase A (MSRA), one of the antioxidant repair enzymes, in SSc, serum anti-MSRA autoantibody levels were examined in patients with SSc by enzyme-linked immunosorbent assay using recombinant MSRA. The presence of anti-MSRA antibody was evaluated by immunoblotting. To determine the functional relevance of anti-MSRA antibody in vivo, we assessed whether anti-MSRA antibody was able to inhibit MSRA enzymatic activity. Serum anti-MSRA antibody levels in SSc patients were significantly higher compared to controls and this autoantibody was detected in 33% of SSc patients. Serum anti-MSRA levels were significantly elevated in SSc patients with pulmonary fibrosis, cardiac involvement, or decreased total antioxidant power compared with those without them. Anti-MSRA antibodies also correlated positively with renal vascular damage determined as pulsatility index by color-flow Doppler ultrasonography of the renal interlobar arteries and negatively with pulmonary function tests. Furthermore, anti-MSRA antibody levels correlated positively with serum levels of 8-isoprostane and heat shock protein 70 that are markers of oxidative and cellular stresses. Remarkably, MSRA activity was inhibited by IgG isolated from SSc sera containing IgG anti-MSRA antibody. These results suggest that elevated anti-MSRA autoantibody is associated with the disease severity of SSc and may enhance the oxidative stress by inhibiting MSRA enzymatic activity.
Arch Dermatol Res 2010 Jan
PMID:Autoantibody against one of the antioxidant repair enzymes, methionine sulfoxide reductase A, in systemic sclerosis: association with pulmonary fibrosis and vascular damage. 1984 33

Systemic sclerosis (SSc) is thought to be an autoimmune disease, as autoantibodies against a variety of extractable nuclear antigens can be detected in patient sera. Subgrouping patients based on the type of autoantibodies present can be useful in diagnosis and management. Anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (anti-topo I) are the classic autoantibodies associated with SSc. ACA are associated with limited cutaneous involvement and isolated pulmonary hypertension, whereas anti-topo I are associated with diffuse skin involvement and pulmonary fibrosis. ACA are predictors for a favorable prognosis, while anti-topo I are correlated with a poor prognosis and SSc-related mortality. Additionally, anti-RNA polymerase antibodies (anti-RNAP) are associated with diffuse cutaneous disease and renal involvement. Anti-nucleolar antibodies define multiple subgroups of patients with SSc. Of these, anti-Th/To antibodies (anti-Th/To) and anti-PM-Scl antibodies (anti-PM-Scl) are associated with limited cutaneous SSc (lSSc), whereas anti-U3RNP antibodies (anti-U3RNP) are associated with diffuse cutaneous SSc (dSSc). In addition, anti-Th/To and anti-U3RNP can be predictors for a less favorable prognosis with a higher frequency of organ involvement, such as pulmonary fibrosis, pulmonary hypertension and renal crisis. Other autoantibodies are less frequently reported: anti-Ku antibodies, anti-U1RNP antibodies, anti-human upstream-binding factor, and anti-U11/U12 antibodies. These antibodies are generally less specific to SSc, but also define clinically distinct patient subsets. Thus, characterization of autoantibodies in SSc together with knowledge of disease characteristics intrinsic to distinct patient populations is helpful for assessing the clinical presentation and prognosis of this disease, and for monitoring patients with SSc.
J Dermatol 2010 Jan
PMID:Autoantibody profiles in systemic sclerosis: predictive value for clinical evaluation and prognosis. 2017 39

The combinational effect of oral corticosteroid and mizoribine for ulcerative colitis is presented in a patient with systemic sclerosis (SSc). A 64-year-old woman came to our clinic complaining of a 30-year history of Raynaud's phenomenon. She had past history of ulcerative colitis with the continued medication of mesalazine without success. She was presented with sclerodactyly and finger joint swelling. She also showed epigastric discomfort. Laboratory study showed positive anti-nuclear antibody and positive anti-centromere antibody. Histological examination showed mild perivascular mononuclear cell infiltrates in the whole dermis and increased deposition of collagen fibers in the middle and lower dermis. Chest X-ray film showed mild bibasilar pulmonary fibrosis. An upper gastrointestinal series study showed reflux esophagitis and atrophic gastritis. These findings led to the diagnosis of systemic sclerosis (limited type) complicated with ulcerative colitis. Treatment with oral corticosteroid (5 mg/day) and mizoribine (150 mg/day) in the morning was started. She showed remarkable improvement for sclerodactyly and lower intestinal bleeding stopped after 6 months. She is under the same treatment without exaggeration and adverse effect of the drug until now.
J Dermatol 2010 Jan
PMID:Combinational effect of low-dose oral corticosteroid and mizoribine for ulcerative colitis in a patient with systemic sclerosis. 2017 41

Hermansky-Pudlak syndrome is an autosomal recessive disorder of lysosomal storage characterized by the triad of occulocutaneous albinism, bleeding diathesis, and pulmonary fibrosis. Sarcoidosis is a disease characterized by the development of noncaseating granulomas, most commonly affecting the lungs. The pathophysiology, histological findings, clinical symptoms, and treatment of the pulmonary manifestations of Hermansky-Pudlak syndrome are distinct from those of sarcoidosis. As patients with occulocutaneous and bleeding manifestations of Hermansky-Pudlak syndrome may also develop pulmonary fibrosis, the authors present this case to illustrate that pulmonary symptoms must be carefully evaluated in those with this syndrome because in this case, the patient developed underlying pulmonary sarcoidosis. To the authors' knowledge, this is the first documented case of Hermansky-Pudlak syndrome with concomitant pulmonary sarcoidosis.
J Clin Aesthet Dermatol 2009 Oct
PMID:A case of hermansky-pudlak syndrome with pulmonary sarcoidosis. 2072 74


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