RESUMO
Dysregulation of Janus kinase (JAK) pathways from uncontrolled cytokine signaling comprises the pathological basis for many complex inflammatory cutaneous disorders. Oral JAK inhibitors, upadacitinib, tofacitinib, and baricitinib targeting JAK 1 and JAK 1/3, respectively, are currently US Food and Drug Administration (FDA)-approved for several rheumatic conditions. However, studies have shown that JAK-mediated signaling pathways are involved in many immune-related dermatologic conditions. As a result, for recalcitrant diseases, JAK inhibitors are potential alternative therapies due to their broad targeted inhibitory mechanisms. In this case series, we present the successful off-label treatment of 6 cases across dermatomyositis, hidradenitis suppurativa, cutaneous lupus, and cutaneous Crohn’s disease, which failed conventional therapies with upadacitinib or tofacitinib. In the 3 dermatomyositis cases, use of upadacitinib or tofacitinib demonstrated positive clinical outcomes, with no recurrent symptoms in cases where upadacitinib was used. In treatment-resistant hidradenitis suppurativa, upadacitinib demonstrated reduced systemic flares and moderate cutaneous symptom improvement. In the case of cutaneous Crohn’s disease, upadacitinib resulted in reduced cutaneous symptoms without new flares. Tofacitinib resulted in completed resolution of cutaneous symptoms in our patient’s case of cutaneous lupus erythematosus. JAK inhibitors upadacitinib and tofacitinib may be potential drug candidates in patients with treatment-resistant disease, especially in cases of inflammatory cutaneous conditions such as dermatomyositis, hidradenitis suppurativa, cutaneous lupus, and cutaneous Crohn’s disease. Further studies with larger sample sizes among these conditions are warranted to assess potential broader applicability of the positive results demonstrated in our patient cases. J Drugs Dermatol. 2023;22(12):1183-1190. doi:10.36849/JDD.7500.
Assuntos
Doença de Crohn , Dermatite , Dermatomiosite , Hidradenite Supurativa , Inibidores de Janus Quinases , Lúpus Eritematoso Cutâneo , Humanos , Inibidores de Janus Quinases/efeitos adversos , Uso Off-Label , Doença de Crohn/tratamento farmacológico , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/tratamento farmacológico , Dermatomiosite/tratamento farmacológico , Dermatite/tratamento farmacológico , Janus Quinases , Lúpus Eritematoso Cutâneo/induzido quimicamenteAssuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Fluoruracila/efeitos adversos , Lúpus Eritematoso Cutâneo/induzido quimicamente , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/secundário , Cisplatino/uso terapêutico , Terapia Combinada , Substituição de Medicamentos , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/administração & dosagem , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Cutâneo/fisiopatologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tolerância a Radiação , Radioterapia Adjuvante , Ribonucleoproteínas/imunologiaRESUMO
Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small cell lung, prostate, gastric, head and neck, and ovarian cancers, as well as in the adjuvant setting for operable node-positive breast cancers. Although the true incidence of dermatological adverse events (AEs) in patients receiving taxanes is not known, and has never been prospectively analysed, they clearly represent one of the major AEs associated with these agents. With an increase in the occurrence of cutaneous AEs during treatment with novel targeted and immunological therapies when used in combination with taxanes, a thorough understanding of reactions attributable to this class is imperative. Moreover, identification and management of dermatological AEs is critical for maintaining the quality of life in cancer patients and for minimizing dose modifications of their antineoplastic regimen. This analysis represents a systematic review of the dermatological conditions reported with the use of these drugs, complemented by experience at comprehensive cancer centres. The conditions reported herein include skin, hair, and nail toxicities. Lastly, we describe the dermatological data available for the new, recently FDA-and EMA- approved, solvent-free nab-paclitaxel.
Assuntos
Antineoplásicos/efeitos adversos , Toxidermias/etiologia , Paclitaxel/efeitos adversos , Taxoides/efeitos adversos , Alopecia/induzido quimicamente , Docetaxel , Edema/induzido quimicamente , Humanos , Lúpus Eritematoso Cutâneo/induzido quimicamente , Doenças da Unha/induzido quimicamente , Transtornos da Pigmentação/induzido quimicamente , Radiodermite/induzido quimicamenteRESUMO
No disponible
Assuntos
Humanos , Masculino , Feminino , Lúpus Eritematoso Cutâneo/induzido quimicamente , Fator de Necrose Tumoral alfa/administração & dosagem , Fator de Necrose Tumoral alfa/efeitos adversos , Autoanticorpos , Autoanticorpos/imunologia , Terapia Biológica/métodos , Terapia Biológica/tendências , Terapia Biológica , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/análise , Receptores do Fator de Necrose TumoralRESUMO
Lesions typical of subacute cutaneous lupus erythematosus developed in an elderly woman after 6 months of PUVA (8-methoxypsoralen and longwave ultraviolet light) therapy for psoriasis. Pancytopenia, antibodies to double-stranded DNA, and hypocomplementemia developed concurrently with the appearance of the cutaneous lesions. With discontinuation of photochemotherapy, the cutaneous lesions disappeared and the pancytopenia improved.
Assuntos
Lúpus Eritematoso Cutâneo/induzido quimicamente , Terapia PUVA/efeitos adversos , Psoríase/tratamento farmacológico , Idoso , Anticorpos Antinucleares/análise , Complemento C3/análise , Feminino , Glucocorticoides/uso terapêutico , Humanos , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Cutâneo/imunologiaRESUMO
We report on a 74-year-old female patient with psoriasis vulgaris who, under PUVA therapy, developed an exanthema with clinical and histological signs of systemic lupus erythematosus. Antibodies to Ro/SSA antigens were not detectable before the onset of the lupus exanthema but showed a high titer afterwards. At that time, we found the typical serological constellation of subacute cutaneous lupus erythematosus.