RESUMO
Aluminum oxyhydroxide (Alhydrogel(®)) is a nano-crystalline compound forming aggregates that has been introduced in vaccine for its immunologic adjuvant effect in 1926. It is the most commonly used adjuvant in human and veterinary vaccines but mechanisms by which it stimulates immune responses remain ill-defined. Although generally well tolerated on the short term, it has been suspected to occasionally cause delayed neurologic problems in susceptible individuals. In particular, the long-term persistence of aluminic granuloma also termed macrophagic myofasciitis is associated with chronic arthromyalgias and fatigue and cognitive dysfunction. Safety concerns largely depend on the long biopersistence time inherent to this adjuvant, which may be related to its quick withdrawal from the interstitial fluid by avid cellular uptake; and the capacity of adjuvant particles to migrate and slowly accumulate in lymphoid organs and the brain, a phenomenon documented in animal models and resulting from MCP1/CCL2-dependant translocation of adjuvant-loaded monocyte-lineage cells (Trojan horse phenomenon). These novel insights strongly suggest that serious re-evaluation of long-term aluminum adjuvant phamacokinetics and safety should be carried out.
Assuntos
Adjuvantes Imunológicos/efeitos adversos , Hidróxido de Alumínio/efeitos adversos , Fasciite/complicações , Miosite/complicações , Vacinas/efeitos adversos , Imunidade Adaptativa/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos/administração & dosagem , Adjuvantes Farmacêuticos/efeitos adversos , Adjuvantes Farmacêuticos/química , Adjuvantes Farmacêuticos/farmacologia , Hidróxido de Alumínio/administração & dosagem , Hidróxido de Alumínio/química , Hidróxido de Alumínio/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Quimiocina CCL2/análise , Transtornos Cognitivos/etiologia , Controle de Doenças Transmissíveis/métodos , Líquido Extracelular/química , Fasciite/sangue , Fasciite/induzido quimicamente , Fasciite/patologia , Fadiga/etiologia , Predisposição Genética para Doença , Humanos , Injeções Intramusculares , Efeitos Adversos de Longa Duração/induzido quimicamente , Macrófagos/ultraestrutura , Dor Musculoesquelética/etiologia , Miosite/sangue , Miosite/induzido quimicamente , Miosite/patologia , Síndrome do Golfo Pérsico/induzido quimicamente , Células Th2/efeitos dos fármacos , Vacinas/administração & dosagem , Vacinas/uso terapêuticoRESUMO
INTRODUCTION: Laminopathies (diseases related to A/C mutations of lamines) are rare genetic diseases with an extensive phenotypic spectrum, including lipodystrophic syndromes-characterized by a selective loss of adipose tissue-of which the partial Dunnigan family type is the most frequent. CASE REPORT: We report on a 55-year-old woman with diabetes and long-term disabling myalgia. Her cushingoid morphotype, associated with cutaneous lipo-atrophy and muscle hypertrophy in addition to a genetic heritage, led us to the diagnosis of complex partial familial lipodystrophy heterozygous LMNA_c.82C>T, p.Arg28Trp mutation. CONCLUSION: Familial partial lipodystrophic syndromes may have varied phenotypes, mainly cardio-metabolic, which could mimic a particularly severe type 2 diabetes. The diagnostic work-up of this disease has to include a careful investigation of gait troubles and paroxysmal conduction that could lead to sudden death, as well as a genetic examination. In some cases, recombinant leptin can be proposed.