Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vulvar cancer is uncommon, accounting for 0.3% of all new US cancer diagnoses. The majority of cases are squamous cell carcinoma. Malignant melanoma is the second most common type. Other cases are related to chronic inflammatory skin disorders such as lichen sclerosus. Vulvar intraepithelial neoplasia (VIN) is a precursor to squamous cell vulvar cancer. It may be the usual type associated with human papillomavirus (HPV) infection, or the differentiated type often associated with chronic skin disorders. Risk factors for VIN are HPV infection, cigarette smoking, chronic skin disorders, and immunosuppression. Symptoms of vulvar cancer include pruritus, bleeding, skin color change, skin lesions, and dysuria. VIN and vulvar cancer are diagnosed by skin biopsy. Treatment of VIN includes wide local excision, via surgical removal or with laser or ultrasonic surgical aspiration procedures. Medical therapy with imiquimod also may be used. Prognosis is good with early detection; the 5-year survival rate for stage I cancer is greater than 85%. Advanced disease has a poor prognosis, with a 5-year survival rate in stage IV disease as low as 5%. Although screening for vulvar cancer is not recommended, clinicians should evaluate and biopsy any suspicious vulvar lesions. Current efforts at prevention are aimed at HPV vaccination.
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PMID:Genital Cancers in Women: Vulvar Cancer. 2656 49

Autotaxin (ATX) is a 125-kD type II ectonucleotide pyrophosphatase/phosphodiesterase (ENPP2 or NPP2) originally discovered as an unknown "autocrine motility factor" in human melanoma cells. In addition to its pyrophosphatase/phosphodiesterase activities ATX has lysophospholipase D (lysoPLD) activity, catalyzing the conversion of lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). ATX is the only ENPP family member with lysoPLD activity and it produces most of the LPA in circulation. In support of this, ATX heterozygous mice have 50% of normal LPA plasma levels. The ATX-LPA signaling axis plays an important role in both normal physiology and disease pathogenesis and recently has been linked to pruritus in chronic cholestatic liver diseases, including primary biliary cholangitis (PBC). Several lines of evidence have suggested that a circulating puritogen is responsible, but the identification of the molecule has yet to be definitively identified. In contrast, plasma ATX activity is strongly associated with pruritus in PBC, suggesting a targetable molecule for treatment. We review herein the biochemistry of ATX and the rationale for its role in pruritus.
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PMID:Autotaxin, Pruritus and Primary Biliary Cholangitis (PBC). 2701 50

The introduction of immunotherapy such as antiprogrammed death1 (anti-PD1) monoclonal antibodies has changed the scenario of treatment in cancer. Apart from their impressive efficacy profiles, they are better tolerated than the anticytotoxic T-lymphocyte-associated protein 4 antibodies. Dermatological adverse events such as pruritus and rash have been reported in various clinical trials. We report three cases of anti-PD1-induced bullous lichen planus (LP)-like reactions encountered in our institution. These patients developed LP-like papules and annular plaques with vesicles or crusted centres. Histology showed LP-like changes with negative immunofluorescence. Vesiculobullous lesions in patients treated with anti-PD1 therapies require a careful clinicopathological evaluation.
Melanoma Res 2016 08
PMID:PD-1 inhibitors induced bullous lichen planus-like reactions: a rare presentation and report of three cases. 2713 55

Inhibition of immune checkpoints using anti-programmed cell death-1 (PD-1) or anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibodies has revolutionized the management of patients with advanced-stage melanoma and is among the most promising treatment approaches for many other cancers. Use of CTLA-4 and PD-1 inhibitors, either as single agents, or in combination, has been approved by the US FDA for the treatment of metastatic melanoma. Treatment with these novel immunotherapies results in a unique and distinct spectrum of adverse events, which are mostly related to activation of the immune system and are, therefore, an unwanted consequence of their mechanisms of action. Adverse effects of CTLA-4 and/or PD-1 inhibition are most commonly observed in the skin, gastrointestinal tract, liver and endocrine systems and include pruritus, rash, nausea, diarrhoea and thyroid disorders. In this Review, the authors describe the adverse event profile of checkpoint inhibitors targeting CTLA-4 and PD-1, used both as monotherapies and in combination and aim to provide some general guidelines, based upon the mechanisms of action of these therapies and on the management of these immune-related adverse events.
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PMID:Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. 2714 85

Vemurafenib is a potent and selective BRAF inhibitor, which is effective on patients with BRAF V600E mutated late-stage melanoma. Common and less common adverse skin reactions include photosensitivity, maculo-papular exanthema, hand-foot skin reactions, hyperkeratotic follicular rash, pruritus, benign verrucous papillomas, plantar hyperkeratosis, keratoacanthomas, squamous cell carcinomas, infections, and melanoma. To our knowledge, vitiligo has been reported in 2 cases only. This paper reports the case of a 63-year-old man with metastatic melanoma, who developed sudden facial depigmentation after 4 weeks of treatment with vemurafenib 960 mg twice daily. Features consistent with vitiligo were evident at clinical and ultraviolet light examination, as well as at in vivo reflectance confocal microscopy. The latter examination showed lack of normal brightly refractile papillary rings at the dermo-epidermal junction in lesional skin, as well as decreased brightness and half-rings with "scalloped border-like" features in adjacent non-lesional skin. Vitiligo is an adverse reaction to be expected in patients treated with vemurafenib and whether its occurrence may be associated with a positive outcome, as suggested by previous investigations, is still a matter of debate. <br /><br /> <em>J Drugs Dermatol. </em>2016;15(6):766-768.
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PMID:Vitiligo of the Face in a Patient Treated With Vemurafenib for Metastatic Melanoma. 2727 87

Dear Editor, Cutaneous metastases (CM) are detected in about 0.6-10.4% of patients with an internal malignancy (1-3). Excluding melanoma, breast and lung carcinomas are the main source of CM in women and men, respectively (1,4,5). CM can have different clinical features, and a diagnosis of CM is usually suspected before performing a biopsy. However, this can be a pitfall for clinicians when the clinical presentation is not the typical inflammatory nodule or mass. Herein we report 2 cases of cutaneous metastases of breast carcinoma, initially treated as a common skin infection. Case 1 A 51-year-old Caucasian woman presented to our Institute with a four-month history of diffuse and erythematous pustular, lesions on the right arm that were painless and non pruritic (Figure 1). The patient had undergone excision for a breast adenocarcinoma (stage IIIA) 5 years earlier. An initial diagnosis of folliculitis was established, and the patient started systemic and topical antibiotics without any improvement. Based on the clinical features and the patient medical history, we performed a skin biopsy. Pathologically dermal nests of tumor cells, arranged in a glandular-like pattern and involving the perifollicular and follicular areas (Figure 2, Figure 3), were highlighted. The tumor cells were positive to cytokeratin (CK) 7, CK19, and carcinoembryonic antigen (CEA) and negative for CK20, CK5/6, CD10, and thyroid transcription factor-1 (TTF-1) (Figure 4). According to the clinical history and pathology, a final diagnosis of folliculotropic metastatic breast carcinoma was established. Unfortunately, the patient died after 10 months. Case 2 A 61-year old Caucasian woman presented to our Department with a two-month history of pink/violet macular lesions with diffuse telangiectasia on the left breast and arm (Figure 5, Figure 6). Five years earlier she had undergone excision for a breast adenocarcinoma (stage II A). A previous diagnosis of cellulitis had been made, and systemic antibiotic therapy had been started without any improvement. Based on the clinical features and the patient medical history, a punch biopsy was performed. Examination of skin biopsy showed a diffuse, sclerotic, and mixoid stroma with several dense ectatic lymphatic vessels (Figure 7, Figure 8). The dermal and hypodermal lymphatic lumens were filled with neoplastic cells. Thus, a diagnosis of cutaneous lymphangitis carcinomatosa (CLC) was established. Unfortunately, the patient died after 8 months. Discussion CM are present after breast carcinoma in about 23.9% of patients, often involving the chest and abdomen and manifesting on average 5 years after surgical removal of the first malignancy (1,6). CM of breast cancer are usually solitary or multiple nodular pinkish lesions (ranging between 1 and 3 cm) (1). However, several clinical features have been reported in the literature, including telangiectatic carcinoma, erythema-like, erythema annulare centrifugum-like, morphea-like, erysipelas-like, dermatofibroma-like, herpes-zoster-like, and alopecia-like lesions (1,7-10). Clinical and pathological images of folliculitis-like metastases are rarely reported in the literature, especially after breast cancer (11,13) Clinically, folliculitis-like metastases could resemble a zosteriform-like metastatic lesion (7,14,15) although they do not follow a dermatome and are pustular lesions rather than violaceous indurate papules and/or nodules (13,14) Pathologically, our cases showed an infiltration of the dermis and pilosebaceous units growing through the pilosebaceous unit in a "pseudo-eruptive way". In this regard, folliculitis-like CM could be similar to alopecia neoplastica, where the metastatic process involves and destroys the pilosebaceous units completely, leading to scarring alopecia (9,10). However, in our case, the pilosebaceous unit was still slightly recognizable, and clinically there were no scar-like features. The mechanism of folliculitis-like metastasis formation is currently unknown. As reported in zosteriform-like metastases, the lymphatic and hematogenous spread of malignant cells or the koebnerization at the site of a previous viral and/or bacterial infection could lead to metastasis (7,14-16). However, unlike zosteriform-like metastases, the spread of neoplastic cells from the dorsal root ganglia was not a plausible mechanism of metastasization in our cases because of the absence of dermatome involvement. Furthermore, there were no signs of possible koebnerization in a previous bacterial and/or viral infection site (7,13) In our opinion, folliculitis-like metastasis may be a result of the skin extruding malignant cells through the pilosebaceous unit to limit the neopalstic proliferation. This could explain the clinical and pathological features of folliculitis-like metastasis. Alternatively, the adnexotropic behavior of malignant cells may be explained by homing mechanisms, involving the up-regulation of the intercellular adhesion molecule 1 (ICAM-1) on the follicular epithelium, such as folliculotropic mycosis fungoides (17). In our patient, the folliculitis-like eruption was the first sign of recurrence after 5 years of disease-free survival. It is evident that the unusual folliculitis-like eruption of CM led to a delay in the diagnosis. CLC is a rare presentation of skin metastasis, characterized by an occlusion of dermic lymphatic vessels by neoplastic cells (18). CLC has been reported in the literature in association with several malignancies, including lung, breast, and ovarian cancer (19). CLC shows pink/violet macular lesions with diffuse telangiectasias, often associated with itching and burning sensation. The main differential diagnoses are erysipelas and cellulitis. However, CLC is not associated with fever, chills, and leukocytosis. Furthermore, CLC shows no response to antibiotic therapies. Several clinicopathological types of cutaneous metastasis have been reported in the literature, including telangiectatic metastatic breast carcinoma (TMBC) and carcinoma erysipelatous (CE). TMBC is characterized by yellowish/reddish or violaceous papulo-vesicular lesions. CE usually shows blistering erythematous eruptions resembling erysipelas. However, CLC, TMBC, and CE are different clinical expressions of the same metastatic process, pathologically characterized by edema of the dermis and ectatic lymphatic vessels. Positivity to CD31 and podoplanin in the endothelial cells shows that the tumor metastatises predominantly via lymphatic vessels (20). In conclusion, we stress that every cutaneous lesion should be studied and examined carefully in patients with a personal history of cancer. Indeed, a correct diagnosis remains the pivotal point for a better management of these patients.
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PMID:Folliculotropic Cutaneous Metastases and Lymphangitis Carcinomatosa: When Cutaneous Metastases of Breast Carcinoma Are Mistaken for Cutaneous Infections. 2747 79

Nivolumab, a programmed death 1 (PD1) inhibitor, belongs to a family of drugs known as immune checkpoint inhibitors that share a similar toxicity profile, which includes rash, pruritus, colitis, hepatitis, pneumonitis and thyroid dysfunction. Nivolumab has a proven efficacy in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. We present the case of a 67-year-old male patient with metastatic squamous cell carcinoma of the lung who suffered from a massive pericardial effusion secondary to treatment with nivolumab, which he began in June 2015. After five cycles the patient was hospitalized due to acute respiratory failure requiring mechanical ventilation. An echocardiogram revealed a massive pericardial effusion with tamponade. After pericardiocentesis and corticosteroid treatment, the patient's condition improved rapidly. A CT scan revealed a response of the tumor. Although anti-PD1 treatment is usually regarded as less toxic than chemotherapy, a wide spectrum of life-threatening immune-related side effects may still occur and clinical vigilance is required.
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PMID:Nivolumab-Induced Pericardial Tamponade: A Case Report and Discussion. 2755 35

Phototherapy is a valuable therapeutic tool in Dermatology, but there may be drawbacks. Acute and long-term adverse effects, of variable severity, include skin erythema, xerosis, pruritus, blistering, altered pigmentation, photoaging, and photocarcinogenesis. Despite concerns over the carcinogenic potential of ultraviolet radiation, most studies have not found an increased risk of non-melanoma or melanoma skin cancer in patients treated with ultraviolet B (broadband and narrowband) and ultraviolet A1 phototherapy. These are therefore considered reasonably safe treatment modalities concerning the development of skin neoplasms, although caution and further investigation are warranted. Photoprotective measures, such as avoidance of concurrent sunlight exposure and covering skin areas not afflicted with disease, or more modern strategies, including phytochemical antioxidants and exogenous DNA repair enzymes, can minimize the hazards of phototherapy. Patients submitted to phototherapeutic regimens should undergo complete, careful dermatologic examination regularly and lifelong.
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PMID:The dark side of the light: Phototherapy adverse effects. 2763 33

We conducted a network meta-analysis in order to compare different strategies for managing melanoma patients. Electronic databases were searched for eligible randomized trials that compared different strategies in efficacy and tolerability. Five interventions were associated with a significant improvement in PFS over chemotherapy (all HR < 1): Ipilimumab, Tremelimumab, Nivolumab, Pembrolizumab 2 mg/kg and Ipilimumab + Nivolumab. Three interventions exhibited significantly improved OS results over chemotherapy (all HR < 1): Ipilimumab, Nivolumab and Ipilimumab + Chemotherapy. Four interventions were superior to chemotherapy in CR and PR (all OR > 1): Nivolumab, Pembrolizumab 10 mg/kg, Pembrolizumab 2 mg/kg and Ipilimumab + Nivolumab. However, the other seven interventions were associated with an increased risk of pruritus compared to chemotherapy (all OR > 1). Ipilimumab, Tremelimumab, Ipilimumab + Nivolumab and Ipilimumab + Chemotherapy might result in a higher risk of diarrhea compared to chemotherapy (all OR > 1). Immune checkpoint therapy or combined interventions might be more effective than chemotherapy for managing melanoma patients. However, chemotherapy appears to be more tolerable than these combined strategies with respect to adverse events.
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PMID:Pharmacological interventions for melanoma: Comparative analysis using bayesian meta-analysis. 2776 96

Increasing use of programmed cell death protein 1/programmed cell death protein 1 ligand inhibition for the treatment of patients with various malignancies such as advanced lung cancer, kidney cancer, and melanoma has resulted in valuable clinical responses, along with the occurrence of new and often puzzling side effects. Known cutaneous effects of CTLA4 and programmed cell death protein 1/programmed cell death protein 1 ligand inhibitors include generalized pruritus, vitiligo, maculopapular lesions, and lichenoid skin eruptions. Alopecia has been the only hair effect previously associated with this class of agents. We describe herein the first case of a persistent curly hair phenotype with the use of nivolumab in a patient with metastatic squamous cell lung cancer.
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PMID:Persistently curly hair phenotype with the use of nivolumab for squamous cell lung cancer. 2782 86


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