Eruptive Nevi Research Articles

Sorafenib-Induced Spiny Follicular Hyperkeratosis: A Case Report with Review of Literature

AbstractSorafenib is a multikinase inhibitor used in the treatment of various solid tumors. Mucocutaneous adverse events are experienced by 70 to 90% of the patients receiving sorafenib, underscoring the importance of awareness among oncologists and dermatologists. Spiny follicular hyperkeratosis (SFH) is a benign and rarely reported skin reaction linked to sorafenib. It is characterized by flesh-colored or white, follicular hyperkeratotic spicules, preferentially involving the face, scalp, upper trunk, and upper arms. Besides being acknowledged as a paraneoplastic cutaneous manifestation of multiple myeloma, SFH has also been linked to a few diseases and drugs, other than sorafenib. However, the precise etiopathogenesis remains to be elucidated. We report an interesting case of SFH in a 14-year-old child, 1 week following the initiation of sorafenib. Trichodysplasia spinulosa, multiple minute digitate hyperkeratosis, keratosis pilaris, filiform warts, and pityriasis rubra pilaris are morphologically similar conditions that were excluded by clinicopathological correlation. A complete resolution of skin rash following sorafenib dose reduction further reinforced our diagnosis. Our patient also developed hand-foot skin reaction, facial erythema, and eruptive nevi during treatment. The regrowth of curly hair following chemotherapy-induced anagen effluvium was an interesting development in our case. We report this case to familiarize clinicians with this rare entity.

Nevoid melanoma and eruptive nevi from erlotinib

Cutaneous side effects such as acneiform eruption, xerosis, and paronychia are frequently observed in patients undergoing treatment with epidermal growth factor receptor (EGFR) inhibitors for non-small cell lung cancer and other solid tumors. Interestingly, these side effects appear to positively correlate with length of remission, indicating that disruption of homeostatic EGFR signaling in the skin may serve as a marker of therapeutic EGFR inhibition in tumors. We report the case of a woman with metastatic lung cancer in remission being treated with the EGFR inhibitor, erlotinib, who experienced numerous commonly occurring adverse cutaneous reactions early in her treatment, and after two years of treatment developed eruptive nevi as well as a nevoid melanoma. Changes in pigmented lesions and the development of melanoma have been described during treatment with the BRAF inhibitor, vemurafenib, and are believed to relate to paradoxical activation of BRAF and the MAPK pathway. We speculate that a similar mechanism may occur during treatment with EGFR inhibitors. Therefore, thorough skin examinations are essential for patients undergoing long term treatment with erlotinib.

Eruptive nevi associated with hydroxyurea

Eruptive nevi associated with hydroxyurea

Eruptive melanocytic nevi after toxic epidermal necrolysis: A case report and literature review

Eruptive melanocytic nevi (EMN), developing after severe bullous disease or adverse drug eruption, are rare. We report a case involving a 20-year-old female student who had an episode of toxic epidermal necrolysis. She developed EMN on her limbs and abdomen half a year after recovery. The nevi appeared rapidly over several months, eventually stabilizing over the ensuing 3 years. Dermoscopy showed regular pigmented networks, which were pathologically consistent with junctional nevus. Although most eruptive nevi were stable in number and morphology, there was one previous report of malignant transformation. Patients with this condition should thus be closely followed.

Eruptive nevi after burn injury

Eruptive melanocytic nevi (EMN) is an unusual phenomenon characterized by the abrupt development of multiple melanocytic nevi over weeks to months in association with an underlying trigger. The underlying mechanisms are not fully understood, however, they have been associated with a variety of conditions. EMN is relatively uncommon and might be underreported due to the absence of close monitoring, insufficient recognition, and the presumed benign course of the condition. We describe the first case report of acral EMN associated with a burn wound on a 2-year-old child. Familiarity is important to differentiate EMN from neoplasms.

Melanocytic nevus count and dermoscopic features do not differ in psoriatic patients undergoing biological agent versus conventional drug therapy

Psoriasis is a chronic immune-mediated disease and treatment of psoriasis includes conventional immunosuppressive agents and biological agents. There are a few data on the relationship between psoriasis and melanocytic lesions. Either benign or malignant proliferations may be seen with immunosuppressive treatment. Eruptive nevi and malignant melanoma (MM) have been reported also associated with biological agents There is raising link biological treatment and malignancies. The objective of this paper is to examine the effects of biological agents versus conventional drugs on melanocytic nevi count and dermoscopical features. Sixty-seven patients receiving TNF-α antagonists (etanercept, infliximab and adalimumab) and 62 patients receiving methotrexate and cyclosporin included to the trial. Duration of treatment with biological agents ranged from 6 months to 4 years, and between 6 months to 3 years for conventional drugs. Total and regional nevi count and structurel changes of biological treatment was evaluated. All melanocytic lesions checked for dermoscopic features by using Dermogenius Ultra (Linos Photonics GmbH & Co, Munich, Germany). Diagnosis of atypical nevi and doubtful lesions for melanoma was made by using ABCD clinically and, by three point check list (asymmetry, atypical pigment network and blue whitish structures) dermoscopically. There were no significant changes in number of total and regional nevi count and in the dermoscopic features of nevi between biological and conventional treatment groups. We observed dermoscopical changes in only one nevus of a patient receiving etanercept. Histopathological examination of this nevi confirmed the diagnosis of dysplastic nevi. There were no MM and non-melanoma skin cancers in both groups. We did not observe significant changes in biological and conventional treatment groups there is a need for further studies to determine long-term effects of biological agents on the melanocytic lesions in patients with psoriasis.

The Effects of Biological Agents on Melanocytic Nevi: A Preliminary Report

during the biological agent therapy. Methods: For this purpose, 40 index nevi of 25 adult patients who were treated with infliximab, adalimumab, etanercept or rituximab were included in this study. All of the patients underwent clinical and dermoscopic evaluation before the beginning of the treatment, 6 months and 1 year after the beginning of the treatment. Among dermoscopic examination methods, pattern analysis, ABCD score system and threepoint checklist were performed. Results: In terms of the diameter of the index nevi, there was no statistically significant difference between the first examination and that of the sixth month, but differences was observed between the first examination and that of the twelfth month. There was also no statistically significant difference in total dermoscopy scores calculated by ABCD score system application on 31 nevi at the times of assessment. At the end of the study, we detected 24 new nevi formation in 7 patients, whom all of were over 35 years of age, however no eruptive nevi or melanoma formation were observed. Conclusion: An increase in the diameters of the present nevi and formation of new nevi may be seen with biological agent therapy in one-year-follow-up.

Prospective study of cutaneous side-effects associated with the BRAF inhibitor vemurafenib: a study of 42 patients

BackgroundBRAF inhibitors are being developed for the treatment of metastatic melanoma harboring a V600E mutation. The use of vemurafenib significantly increases progression-free survival (PFS) and overall survival (OS) in this population of patients, but is associated with numerous adverse skin reactions. Patients and methodsWe carried out a systematic dermatologic study of 42 patients treated with vemurafenib. We collected detailed dermatologic symptoms, photos and biopsy specimens of the skin lesions which enabled us to classify the side-effects. The management and evolution of the skin symptoms are also reported. ResultsAll patients presented with at least one adverse skin reaction. The most common cutaneous side-effects consisted in verrucous papillomas (79%) and hand–foot skin reaction (60%). Other common cutaneous toxic effects were a diffuse hyperkeratotic perifollicular rash (55%), photosensitivity (52%) and alopecia (45%). Epidermoid cysts (33%) and eruptive nevi (10%) were also observed. Keratoacanthomas (KA) and squamous cell carcinoma (SCC) occurred in 14% and 26% of the patients, respectively. ConclusionsThese cutaneous side-effects are cause of concern due to their intrinsic potential for malignancy or because of their impact on patients' quality of life. Management of this skin toxicity relies on symptomatic measures and sun photoprotection.

Flexural Agminated Eruptive Nevi in Langerhans Cell Histiocytosis

Flexural Agminated Eruptive Nevi in Langerhans Cell Histiocytosis

Eruptive nevi in prostate cancer: is this a paraneoplastic phenomenon?

Eruptive nevi in prostate cancer: is this a paraneoplastic phenomenon?

Epidermolysis bullosa simplex, Dowling–Meara type with eruptive nevi

Epidermolysis bullosa simplex, Dowling–Meara type with eruptive nevi

Eruptive multiple Spitz nevi in a patient with epilepsy and drug addiction

Eruptive multiple Spitz nevi in a patient with epilepsy and drug addiction

A Phase 1 Study of DCC-2036, a Novel Oral Inhibitor of BCR-ABL Kinase, in Patients with Philadelphia Chromosome Positive (Ph+) Leukemias Including Patients with T315I Mutation

Abstract 601 Background.DCC-2036 is a novel and potent tyrosine kinase inhibitor (TKI) which binds to a novel region called the switch pocket, thereby preventing BCR-ABL from adopting a conformationally active state. Efficacy against multiple imatinib-resistant BCR-ABL mutants has been demonstrated both in vitro and in vivo (Chan et al., Cancer Cell 2011;19:556). Importantly, DCC-2036 retains full potency against the T315I mutant in preclinical efficacy studies. Methods.This study was designed to find the maximal tolerated dose (MTD) of DCC-2036 when administered daily as a single-agent on a 28-day cycle. Eligible patients included adults with Ph+ CML/ALL who were refractory/intolerant to ≥2 TKI’s or were T315I positive. Initially DCC-2036 capsules were administered orally once daily (QD) at increasing dose levels. Only 1 patient was enrolled in each of the lowest dose cohorts of 57mg QD and 114 mg QD. For higher doses, 3– 6 patients were enrolled into each ascending dose cohort with standard dose limiting toxicity (DLT) rules evaluating safety in cycle 1 to determine dose escalation. A transition from unformulated capsules (C) to formulated tablets (T) occurred after the 1200 mg QD dose level. Paired blood samples were obtained for PK and PD assessments. Results.30 patients (16 males, 14 females; median age 59, range 31 – 80) with CML including 19 in Chronic (CP); 8 in Accelerated (AP) and 3 in Blast (BP) Phase were enrolled. Enrolled patients had received 1–6 prior CML treatments, and 11 patients had the T315I mutation. To date, a total of 212.5 (median 5.6; range 0.2 – 23.4) 28-day cycles were administered over 10 dose levels either as C (7 dose levels) or T (3 dose levels). The 7 C dose levels were studied first and included 57 mg QD through 1200 mg QD. Following transition to T, evaluation continued with 100 mg QD, 100 mg twice daily (BID), and 200 mg BID. Two reversible DLTs (Grade 3 peripheral neuropathy and Grade 4 lower extremity weakness) occurred during the initial treatment cycle at the 200 mg T BID dose level. Evaluation of 6 patients at the 150 mg T BID dose level determined that dose to be the MTD.Preliminary safety data show that other Grade (Gr) 3/4 adverse events (AEs) were Gr 3 slurred speech and Gr 3 eruptive nevi. Gr 1/2 AEs included dry mouth, constipation, diarrhea, paresthesias, and retinal vein occlusion. There was 1 case of Gr 2 pancreatitis that recurred on rechallenge in a patient with previous pancreatitis with nilotinib.Preliminary responses include one major molecular response in a CP patient with T315I mutation who started on capsules and transitioned to 100 mg T QD. There was one complete cytogenetic response in a CP patient at 100 mg T BID, and one partial cytogenetic response in a CP patient who started on capsules and transitioned to 100 mg T BID. One patient with AP CML and T315I mutation had a complete hematologic response at 450 mg C QD. Another patient with AP CML had a partial hematologic response after receiving 200 mg BID for 1 cycle and then downdosing to 100 mg T BID. Four out of 8 patients receiving 100 mg tablets and evaluable for efficacy (completed 3 cycles of treatment) had responses.PK results indicate dose-related, nonlinear increases in both peak plasma concentration (Cmax) and exposure (AUC). PD results reveal both acute and steady state post-treatment reductions in phospho-protein levels on Days 1 and 8. Marked reductions in pSTAT5 and pCRKL have been observed in subjects with both CP and AP and appear to be required for clinical response. Conclusion.The MTD of DCC-2036 tablets is 150 mg BID. Preliminary results suggest that DCC-2036 is well tolerated and has anti-leukemia activity in subjects with refractory CML and T315I positive disease. PD results are consistent with inhibition of BCR-ABL signaling in this first-in-man study of a switch pocket tyrosine kinase inhibitor. Disclosures:Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Chemgenex: Consultancy, Research Funding; Deciphera Pharmaceuticals: Research Funding. Bixby:Novartis: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; GlaxoSmithKline: Speakers Bureau. Rafferty:Deciphera Pharmaceuticals: Employment. Berger:Deciphera Pharmaceuticals: Employment. Wise:Deciphera Pharmaceuticals LLC: Employment. Rutkoski:Deciphera Pharmaceuticals: Employment. Smith:Deciphera Pharmaceuticals: Employment. Van Etten:Deciphera Pharmaceuticals: Consultancy, Research Funding.

Diffuse Dermal Melanocytosis: Follow-up 30 Years Later With Novel Findings of Eruptive Blue Nevi

Diffuse Dermal Melanocytosis: Follow-up 30 Years Later With Novel Findings of Eruptive Blue Nevi

Eruptive nevi following bone marrow transplantation: a reflectance confocal microscopy study

Eruptive nevi following bone marrow transplantation: a reflectance confocal microscopy study

Identification of BRAF mutations in eruptive melanocytic nevi: new insights into melanomagenesis?

Evaluation of: Sekulic A, Colgan MB, Davis MD et al. Activating BRAF mutations in eruptive melanocytic naevi. Br. J. Dermatol. 163(5), 1095–1098 (2010).Eruptive melanocytic nevi (EMN) is an unusual phenomenon characterized by the abrupt, simultaneous appearance of hundreds of melanocytic nevi on previously uninvolved sun-exposed skin. The mechanisms underlying this phenomenon are not well understood, but have been associated with both systemic immunosuppression and bullous dermatoses. The paper under evaluation brings new insight into the molecular events underlying EMN development in a patient receiving 6-mercaptopurine immunosuppressive therapy for ulcerative colitis. Sequencing of DNA from 20 eruptive nevi revealed the presence of BRAF V600E mutations in 85% of the lesions tested. The role of mutated BRAF in the initiation and progression of melanoma in conjunction with the strong correlation between nevus number and melanoma risk suggests the need for photoprotection in patients receiving thiopurine therapy. The study under evaluation further points to the possible interaction between environmental mutagens and UV radiation in the acquisition of BRAF mutations that may in turn increase the risk of melanoma development.

Eruptive Nevi in a Patient Receiving Cyclosporine A for Psoriasis Treatment

Eruptive Nevi in a Patient Receiving Cyclosporine A for Psoriasis Treatment

α-Melanocyte-Stimulating Hormone–Induced Eruptive Nevi

Synthetic peptides that target proopiomelanocortin receptors are being investigated as a novel and safe way to tan. It has been postulated that synthetic alpha-melanocyte-stimulating hormone (alpha-MSH) peptides may have protective effects against the development of melanoma because of their melanogenic activity. Their ultimate biological effect, however, especially in patients with dysplastic nevi or previous melanoma, has yet to be determined. A 40-year-old white man with a history of melanoma and multiple dysplastic nevi self-administered synthetic alpha-MSH. He developed crops of new pigmented nevi, many of which had atypical clinical and histopathologic features. The preexisting nevi became darker and acquired growth features. After alpha-MSH use was discontinued, the nevi progressively lightened and lost their growth features. Synthetic alpha-MSH peptides can drive proliferation of neoplastic melanocytic cells in predisposed patients. This could present an increased risk for melanoma development.

Eruptive melanocytic nevi in patients with renal allografts: Report of 10 cases with dermoscopic findings

Eruptive nevi have been reported after renal allograft transplantation, particularly in children and adolescents, and immunosuppression has been suggested to favor both benign and malignant melanocyte proliferation. In this study, we describe the dermoscopic features of eruptive melanocytic nevi in 10 children, adolescents, and young adults with renal allografts in whom multiple melanocytic nevi developed during a short period after transplantation. Dermoscopy of the eruptive pigmented lesions revealed a peripheral rim of brown globules. This rim of peripheral globules was present in 80% of the patients with eruptive nevi and in most of the lesions of the same patient. The other standard dermoscopic criteria for melanocytic nevi were normal. In our study, we confirm previous reports concerning the development of eruptive nevi in children and adolescents receiving immunosuppressive therapies. In particular, we showed by dermoscopy the presence of a characteristic symmetrical rim of peripheral brown globules. This finding is consistent with the hypothesis that a symmetrical peripheral rim of globules may indicate rapid enlargement of melanocytic lesions. Moreover, we have identified a new group of patients characterized by this dermoscopic feature. These patients are children, adolescents, and young adults with renal allografts receiving immunosuppressive therapy and it is plausible that this dermoscopic characteristic may be found in eruptive nevi developed in association with immunosuppression from any cause.

Widespread eruptive dermal and atypical melanocytic nevi in association with chronic myelocytic leukemia: case report and review of the literature

Eruptive nevi have been associated with local skin trauma and immunosuppression, and atypical eruptive nevi preceding melanoma have been reported in immunocompromised transplant patients. We describe a 25-year-old man with widespread eruptive atypical and dermal melanocytic nevi in association with chronic myelocytic leukemia. Our patient's disease differs from earlier reports of eruptive nevi because his nevi appeared before induction chemotherapy. Eruptive nevi may have been a prodrome to leukemia in this patient. His nevi were histologically similar to eruptive atypical nevi observed in AIDS patients and may imply a link between systemic immunosuppression and melanocyte proliferation. We suggest that patients in whom eruptive nevi develop in association with immunosuppression should be carefully observed for the development of melanoma skin cancer.