Assuntos
Melanoma , Paniculite , Neoplasias Cutâneas , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Paniculite/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Mutação , Neoplasias Cutâneas/tratamento farmacológico , Piridonas , Oximas/uso terapêuticoAssuntos
Macrófagos , Paniculite , Humanos , Paniculite/induzido quimicamente , Feminino , Idoso , Erupção por DrogaRESUMO
A 51-year-old man with a 3-year history of exogenous testosterone pellet injections to the left buttock presented for routine skin examination. While the patient reported recurrent drainage from the site of testosterone replacement therapy (TRT) injections, he continued to receive repeated implantations every 6 months. On physical examination, a 12-mm irregular, brown macule was identified within a poorly demarcated, ecchymotic, and fluctuant subcutaneous plaque on the left buttock with a sinus tract draining serosanguinous fluid. The pigmented lesion was biopsied, revealing malignant melanoma in situ; hence, a wide local excision was scheduled. During the procedure, necrotic subcutaneous fat was observed surrounding the site of biopsy, and a region measuring 18 cm2 approximately was debrided and submitted for pathologic evaluation. Histopathologic examination revealed a diffused subcutaneous granulomatous infiltrate with septal and lobular panniculitis and fat necrosis as well as peripherally palisading histiocytes and hemosiderin deposition (Figures 1A and B). Similar findings were observed in another specimen from the same segment of debrided tissue, compatible with granulomatous panniculitis. Periodic acid-Schiff (PAS), Gram's, and acid-fast bacilli (AFB) stains revealed no microorganisms. During surgical exploration, six foreign bodies were discovered and identified as undissolved testosterone pellets. The patient was referred to a wound care center, but ultimately lost to follow-up.
Assuntos
Paniculite , Testosterona , Masculino , Humanos , Pessoa de Meia-Idade , Testosterona/efeitos adversos , Paniculite/induzido quimicamente , Gordura Subcutânea , Inflamação , Biópsia , CorantesRESUMO
BACKGROUND: BRAF and MEK inhibitors have changed the landscape of treatment for advanced melanoma. Among their side effects, panniculitis has been hypothesized to be associated with better survival. OBJECTIVES: In this study, we aimed to explore the association between the occurrence of panniculitis during targeted therapy and outcome of metastatic melanoma. MATERIALS & METHODS: This was a retrospective single-centre comparative study from 2014 to 2019. An English literature review was also conducted to further our understanding of the mechanism(s) involved and identify characteristics of this association, in order to support better management. RESULTS: Ten patients who developed panniculitis during treatment were matched to 26 controls based on potential confounders at treatment introduction. The prevalence of panniculitis was 5.3%. Median progression-free survival (PFS) for all patients was 8.5 months (range: 3.0-94.0). The median PFS for the group with panniculitis was 10.5 months (7.0-undefined) and 7.0 months (6.0-32.0) for controls (p=0.39). According to the scientific literature, panniculitis occurring during targeted therapy affects mainly young people, predominantly women, with variable delay to onset (with half reported cases occurring in the first month). In addition, panniculitis usually only affects the lower limbs or is associated with other clinical signs (fever, arthralgia), without histological specificity. Discontinuation of targeted therapy is not required as spontaneous remission is usually experienced. Symptomatic treatment may be administered but systemic corticosteroids have not been proven to be effective. CONCLUSION: In contrast to the belief that there is a link between panniculitis and clinical response to targeted therapy according to the literature, our results show that there is no significant association between the two.
Assuntos
Melanoma , Paniculite , Humanos , Feminino , Adolescente , Masculino , Estudos Retrospectivos , Remissão Espontânea , Melanoma/tratamento farmacológico , Artralgia , Paniculite/induzido quimicamenteAssuntos
Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Paniculite , Triazinas , Humanos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Pirazóis/uso terapêutico , Pirróis/efeitos adversos , Paniculite/induzido quimicamente , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/efeitos adversos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/uso terapêuticoAssuntos
Linfoma Cutâneo de Células T , Linfoma de Células T , Paniculite , Neoplasias Cutâneas , Humanos , Metotrexato/efeitos adversos , Paniculite/induzido quimicamente , Paniculite/diagnóstico , Linfoma de Células T/diagnóstico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/complicações , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/complicações , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/tratamento farmacológico , Diagnóstico DiferencialAssuntos
Paniculite , Neoplasias Cutâneas , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêutico , Mutação , Paniculite/induzido quimicamente , Paniculite/diagnóstico , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/uso terapêutico , Neoplasias Cutâneas/induzido quimicamenteRESUMO
The extended-release formulation of exenatide for treatment of Type II diabetes mellitus is encapsulated in microspheres composed of poly(d,l-lactide-co-glycolide) (PLGA) and administered weekly. This medication has been reported to potentially cause injection-site reactions such as pruritus, transient nodules, and foreign body reaction. Here, we report a case of exenatide-induced granulomatous panniculitis. Our patient is a 63-year-old female with Type II diabetes presenting for concerns about painful nodules on her abdomen, developing approximately every week over the past year and migrating. Of note, the lesions appeared following exenatide injections in the same locations. Two deep-seated nodules of 1 cm were identified on examination. There were no overlying skin changes, and the lesions were tender to palpation. Punch biopsies of the two lesions were performed, which revealed a septal panniculitis containing amorphous material, along with a mixed inflammatory infiltrate. Gomori methenamine silver (GMS) and acid-fast bacilli (AFB) stains were negative for organisms. On infrared (IR) spectroscopy examination of the biopsy tissue, the spectral characteristics of (tissue) protein and PLGA were seen. Evaluation of the clinical and histopathologic findings, along with the IR spectroscopy match, determined that exenatide-induced panniculitis was the cause of the patient's nodules. This case highlights the importance of clinicians' awareness regarding injection-site reactions.
Assuntos
Diabetes Mellitus Tipo 2 , Paniculite , Diabetes Mellitus Tipo 2/tratamento farmacológico , Exenatida/efeitos adversos , Feminino , Humanos , Microesferas , Pessoa de Meia-Idade , Paniculite/induzido quimicamente , Paniculite/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/uso terapêuticoRESUMO
Ponatinib is a tyrosine kinase inhibitor (TKI) approved for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia and acute lymphoblastic leukemia. Common adverse effects of ponatinib include neutropenia, arterial thrombosis, and hypertension. We describe a 49-year-old woman who developed panniculitis after brief treatment with ponatinib. In addition, we summarize other studies describing TKI-associated panniculitis.
Assuntos
Antineoplásicos/efeitos adversos , Imidazóis/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Paniculite/induzido quimicamente , Piridazinas/efeitos adversos , Feminino , Humanos , Pessoa de Meia-IdadeAssuntos
Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Paniculite/induzido quimicamente , Sulfonamidas/efeitos adversos , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Terapia Combinada , Citarabina/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Pessoa de Meia-Idade , Paniculite/diagnóstico , Sulfonamidas/administração & dosagem , Suspensão de TratamentoAssuntos
Antineoplásicos/efeitos adversos , Dasatinibe/efeitos adversos , Erupção por Droga/etiologia , Paniculite/induzido quimicamente , Idoso , Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , MasculinoRESUMO
BRAF and MEK inhibitor combination therapy is the standard treatment for patients with BRAF V600E mutant metastatic melanoma. Neutrophilic panniculitis is a known rare complication of BRAF inhibitor therapy and can act as a potential mimic of melanoma metastases on 18F-FDG PET/CT. In this case series, we present three cases of BRAF inhibitor-induced panniculitis in patients being treated for BRAF-mutant metastatic melanoma and emphasize the use of ultrasound to differentiate between panniculitis lesions, which are typically ill-defined echogenic masses and subcutaneous soft tissue melanoma metastases, which present as hypoechoic vascular masses.
Assuntos
Melanoma , Paniculite , Neoplasias Cutâneas , Fluordesoxiglucose F18 , Humanos , Melanoma/tratamento farmacológico , Mutação , Paniculite/induzido quimicamente , Paniculite/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
A 71-year-old female was diagnosed with localized renal cell carcinoma in July 2008 with subsequent metastasis in 2012 to the right adrenal gland, lungs, and brain. Due to disease progression, she was started on pazopanib 800 mg daily in October 2012. In November 2016, the patient developed an ill-defined, red, 10 × 15 cm indurated plaque on the left lateral upper thigh with a discrete 3 cm firm tender tumor without ulceration. An incisional biopsy was performed and showed panniculitis with features resembling sclerosing lipogranuloma. Alternative causes including rheumatologic disease and trauma were ruled out. We report the first case of pazopanib-induced panniculitis. Key clinical and histopathological features include tender subcutaneous nodules, exclusion of other causes, and fatty microcysts within a densely sclerotic background on pathology. As targeted therapies are becoming increasingly common in the field of oncology, prompt identification and reporting of adverse reactions is critical for proper management.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Indazóis/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Paniculite/induzido quimicamente , Pirimidinas/efeitos adversos , Sulfonamidas/efeitos adversos , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Feminino , Humanos , Indazóis/administração & dosagem , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagemRESUMO
OBJECTIVE: Infiltrated macrophages actively promote perivascular adipose tissue remodeling and represent a dominant population in the perivascular adipose tissue microenvironment of hypertensive mice. However, the role of macrophages in initiating metabolic inflammation remains uncertain. SIRT3 (sirtuin-3), a NAD-dependent deacetylase, is sensitive to metabolic status and mediates adaptation responses. In this study, we investigated the role of SIRT3-mediated metabolic shift in regulating NLRP3 (Nod-like receptor family pyrin domain-containing 3) inflammasome activation. Approach and Results: Here, we report that Ang II (angiotensin II) accelerates perivascular adipose tissue inflammation and fibrosis, accompanied by NLRP3 inflammasome activation and IL (interleukin)-1ß secretion in myeloid SIRT3 knockout (SIRT3-/-) mice. This effect is associated with adipose tissue mitochondrial dysfunction. In vitro studies indicate that the deletion of SIRT3 in bone marrow-derived macrophages induces IL-1ß production by shifting the metabolic phenotype from oxidative phosphorylation to glycolysis. Mechanistically, SIRT3 deacetylates and activates PDHA1 (pyruvate dehydrogenase E1 alpha) at lysine 83, and the loss of SIRT3 leads to PDH activity decrease and lactate accumulation. Knocking down LDHA (lactate dehydrogenase A) or using carnosine, a buffer against lactic acid, attenuates IL-1ß secretion. Furthermore, the blockade of IL-1ß from macrophages into brown adipocytes restores thermogenic markers and mitochondrial oxygen consumption. Moreover, NLRP3 knockout (NLRP3-/-) mice exhibited reduced IL-1ß production while rescuing the mitochondrial function of brown adipocytes and alleviating perivascular adipose tissue fibrosis. CONCLUSIONS: SIRT3 represents a potential therapeutic target to attenuate NLRP3-related inflammation. Pharmacological targeting of glycolytic metabolism may represent an effective therapeutic approach.