RESUMO
Pyoderma gangrenosum (PG) may be associated with inflammatory disorders and haematological conditions such as monoclonal gammopathy of uncertain significance (MGUS). We report the case of a 53-year old man who had PG and MGUS. After treatment with infliximab for the PG, he developed myeloma. The course of events in this case suggests that infliximab facilitated the progression from MGUS to myeloma.
Assuntos
Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Hipergamaglobulinemia/complicações , Imunoglobulina A , Mieloma Múltiplo/induzido quimicamente , Pioderma Gangrenoso/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Progressão da Doença , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Lesões Pré-Cancerosas/patologiaRESUMO
Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.
Assuntos
Fumarato Hidratase/genética , Neoplasias Renais/genética , Leiomiomatose/genética , Mutação , Neoplasias Cutâneas/genética , Neoplasias Uterinas/genética , Erros Inatos do Metabolismo dos Aminoácidos/genética , Sequência de Aminoácidos , Estabilidade Enzimática , Feminino , Fumarato Hidratase/química , Fumarato Hidratase/deficiência , Fumarato Hidratase/metabolismo , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Neoplasias Renais/secundário , Leiomiomatose/patologia , Dados de Sequência Molecular , Conformação Proteica , Estabilidade de RNA , RNA Mensageiro/metabolismo , Homologia de Sequência de Aminoácidos , Neoplasias Cutâneas/patologia , Neoplasias Uterinas/patologiaAssuntos
Doenças do Pênis/patologia , Dermatopatias Papuloescamosas/patologia , Úlcera Cutânea/patologia , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Necrose , Dor/etiologia , Doenças do Pênis/complicações , Recidiva , Dermatopatias Papuloescamosas/complicações , Dermatopatias Vasculares/patologia , Úlcera Cutânea/complicações , Gastropatias/complicações , Gastropatias/patologiaRESUMO
We report two cases of Apert's syndrome, each of whom developed the severe acne in adolescence which is a feature of this disorder. Both responded to isotretinoin therapy. Immunohistochemical techniques, using a mouse monoclonal antibody, were employed to stain sebocyte androgen receptors in the two patients, and in five controls. This showed no difference in the number of cells with androgen receptor expression between the patients with Apert's syndrome and controls. These results support the concept that the underlying problem in Apert's syndrome is an abnormal sensitivity to normal circulating levels of androgens, and not an excess number of androgen receptors.
Assuntos
Acne Vulgar , Acrocefalossindactilia , Receptores Androgênicos/análise , Glândulas Sebáceas/química , Acne Vulgar/patologia , Acrocefalossindactilia/patologia , Adolescente , Feminino , HumanosAssuntos
Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Feminino , Humanos , Lactente , Perna (Membro)RESUMO
We report three patients with notalgia paraesthetica. In two of our cases amyloid deposits were found on skin biopsy. Symptoms had been present in both cases for a number of years. It is well recognized that the amount of amyloid present in macular amyloid is often very small and difficult to detect. We suggest that many cases of long-standing notalgia paraesthetica may result in the formation of amyloid, possibly secondary to chronic friction.
Assuntos
Amiloidose/complicações , Dor nas Costas/etiologia , Prurido/etiologia , Dermatopatias/complicações , Idoso , Amiloidose/patologia , Feminino , Humanos , Prurido/patologia , Dermatopatias/patologiaRESUMO
A case of pyoderma gangrenosum of the lip occurring in association with paroxysmal nocturnal haemoglobinuria is described. This is an extremely rare association, which has been documented in the literature on only two previous occasions. Pyoderma gangrenosum (PG) is an uncommon ulcerative skin disorder of unknown aetiology. Its clinical appearance is often distinctive, with established lesions consisting of a necrotic ulcer surrounded by a ragged undermined violaceous edge. Lesions are usually painful and are most often found on the lower limbs but can occur on the trunk, head and neck. The diagnosis is essentially clinical as there are no characteristic histopathological changes. Since its original description in 1930, PG has been frequently associated with a number of underlying systemic diseases. Foremost among these are inflammatory bowel disease and inflammatory polyarthritis. The association with haematological disorders is also well recognized, and includes acute and chronic lymphocytic and myeloid leukaemias, polycythaemia rubra vera, myelofibrosis, myelodysplastic syndrome, essential thrombocythaemia, hypogammaglobinaemia, monoclonal gammopathy, multiple myeloma and non-Hodgkin's lymphoma. We report a case of PG occurring on the lower lip of a 26-year-old man recently diagnosed as having paroxysmal nocturnal haemoglobinuria (PNH).
Assuntos
Hemoglobinúria Paroxística/complicações , Doenças Labiais/complicações , Pioderma Gangrenoso/complicações , Adulto , Hemoglobinúria Paroxística/patologia , Humanos , Lábio/patologia , Doenças Labiais/patologia , Masculino , Pioderma Gangrenoso/patologiaAssuntos
Carcinoma de Células Escamosas/etiologia , Ceratoacantoma/patologia , Terapia PUVA/efeitos adversos , Dermatopatias/tratamento farmacológico , Neoplasias Cutâneas/etiologia , Idoso , Carcinoma de Células Escamosas/patologia , Humanos , Masculino , Pele/patologia , Neoplasias Cutâneas/patologiaRESUMO
A case of acrokeratoelastoidosis (AKE) is reported. A review of the literature has established that at least three clinicopathological entities have been reported under this term. Two of the entities show a combination of hyperkeratosis with fragmentation of dermal elastic tissue, which justifies the designation AKE. The first, for which the term familial AKE is perhaps appropriate, though many cases have been sporadic, begins in childhood or early adult life, and there is no evidence that trauma or light exposure are factors in its production. The second is a more variable clinical syndrome occurring in middle or late adult life, and both physical trauma and light exposure appear to be concerned in its induction. The third syndrome to be reported under the designation AKE shows no abnormality of elastic tissue and appears to be a separate entity.