Patrick Disdier

Cannabis arteritis revisited: Ten new case reports

The purpose of this paper was to revisit the old concept of cannabis arteritis first described in the 1960s and report 10 new cases. Ten male patients, with a median age of 23.7 years developed subacute distal ischemia of lower or upper limbs, leading to necrosis in the toes and/or fingers and sometimes to distal limb gangrene. Two of the patients also presented with venous thrombosis and three patients were suffering from a recent Raynauds phenomenon. Biological test results did not show evidence of the classical vascular risk factors for throm bosis. Arteriographic evaluation in all cases revealed distal abnormalities in the arteries of feet, legs, forearms, and hands resembling those of Buergers disease. A collateral circulation sometimes with opacification of the vasa nervorum was noted. In some cases, arterial proximal atherosclerotic lesions and venous thrombosis were observed. All patients were moderate tobacco smokers and regular cannabis users. Despite treatment with ilomedine and heparin in all cases, five amputations were necessary in four patients. The vasoconstrictor effect of cannabis on the vascular system has been known for a long time. It has been shown that delta-8- and delta-9-tetrahydrocanabinols may induce peripheral vasoconstrictor activity. Cannabis arteritis resembles Buergers disease, but patients were moderate tobacco smokers and regular cannabis users. These cases show that prolonged use of cannabis could be an additive risk factor for juvenile and young adult arteritis. Cannabis arteritis is a forgotten and severe occlusive vascular disease occurring in young adults. Search for cannabis use may be an important tool for a better knowledge of arteritis in young smokers.

Prevalence and Signification of Antinuclear and Anticardiolipin Antibodies in Patients with Epilepsy

PURPOSE To determine the prevalence of autoantibodies in patients with epilepsy and to find a possible relationship between antinuclear antibodies (ANA) and/or anticardiolipin (aCL) antibodies and epilepsy. PATIENTS AND METHODS One hundred sixty-three consecutive, unselected patients followed at the Centre Saint-Paul, a French medical center specialized in epilepsy, were included in the study. IgG and IgM class aCL antibodies were measured by an enzyme-linked immunosorbent assay (ELISA). IgG class ANA was detected by an indirect immunofluorescence technique with Hep2 cells as the substrate. Sera from 100 healthy blood donors, matched for age and sex, were used as controls. RESULTS In 31 sera, IgG class a aCL antibodies were detected at a value higher than 17 GPL unit (19%, P = 0.0003); 10 of them had a value higher than 35 GPL unit. IgM class aCL antibodies were not detected at a significant value. For 6 of the 31 sera, there was a beta 2-glycoprotein I dependence. None of the patients with aCL antibodies in the serum had a past history of deep venous or arterial thrombosis. ANA were detected in the sera from 41 patients (25%, P < 0.005). The presence of autoantibodies in the serum was not statistically dependent on the type of epilepsy, the kind of antiepileptic drug, or the age or sex of the patients. CONCLUSIONS Our study suggests that there is a relationship between epilepsy and aCL antibodies, even in the patients without systemic lupus erythematosus. Large prospective studies are needed to define the role of the aCL antibodies and ANA in pathophysiology of epilepsy.

CIAS1 Mutation in a Patient with Overlap between Muckle-Wells and Chronic Infantile Neurological Cutaneous and Articular Syndromes

The Muckle-Wells syndrome is a rare autosomal dominant disorder belonging to the group of hereditary fever syndromes. The chronic infantile neurological cutaneous and articular (CINCA) syndrome is a systemic inflammatory disorder of unknown etiology with neonatal onset. They are considered as two different entities. We report the case of a 36-year-old man suffering since birth from a nonpruritic generalized urticaria, with inflammatory flares, joint manifestations and progressive deafness requiring a bilateral hearing aid. An initial diagnosis of Muckle-Wells syndrome was made. However, the patient had an unusual clinical presentation with slightly dysmorphic facial appearance, clubbing of the fingers, mild mental retardation and papilledema. After a genetic advice, a diagnosis of CINCA syndrome was made. Search for mutations in the CIAS1 gene revealed a new mutation in a heterozygous state. This case report really raises the question of a link between these two inflammatory diseases. Further studies are needed to confirm the involvement of mutations of the CIAS1 gene in CINCA syndrome.

Lysozyme amyloidosis: report of 4 cases and a review of the literature.

Abstract: Autosomal dominant hereditary amyloidosis represents not 1 disease but a group of diseases, each the result of mutations in a specific protein. The most common form is transthyretin amyloidosis, which has been recognized clinically for over 50 years as a familial polyneuropathy. Nonneuropathic amyloidoses (Ostertag type amyloidosis) include those due to abnormalities in lysozyme, fibrinogen Aα-chain, and apolipoprotein A-I and A-II. The role of lysozyme in amyloid-related human disorders was first described in 1993; to date, there have been only 9 publications describing this disorder, which is a nonneuropathic form of hereditary amyloidosis. Reported cases have involved 7 unrelated families. We describe here our own experience with 4 families suffering from lysozyme amyloidosis: the first had prominent renal manifestations with sicca syndrome, the second and third had prominent gastrointestinal symptoms, and the fourth had a dramatic bleeding event due to rupture of abdominal lymph nodes. To our knowledge, this last symptom has not been reported previously, but is reminiscent of the hepatic hemorrhage seen in a previously reported case of a patient with lysozyme amyloidosis. To characterize the manifestations of this disorder, we performed an exhaustive literature review. Although hereditary amyloidosis is thought to be a rare disease, it is probably not as rare as we think and may well be underdiagnosed. Moreover, some cases of lysozyme amyloidosis are probably confused with acquired monoclonal immunoglobulin light-chain (AL) amyloidosis, formerly known as primary amyloidosis, which is the most frequent type of amyloidosis. Because treatment for each type of amyloidosis is different, and because therapy directed at 1 type may worsen symptoms of the other types, it is important to determine precisely the nature of the amyloid protein. Thus, hereditary lysozyme amyloidosis should be considered in all patients with systemic amyloidosis, particularly in patients who present with renal, gastrointestinal, or bleeding complications without evidence of AL or AA (secondary) amyloidoses. Abbreviations: AA amyloidosis = secondary amyloidosis, AL amyloidosis = acquired monoclonal immunoglobulin light-chain amyloidosis (formerly primary amyloidosis), apo = apolipoprotein, GI = gastrointestinal.

Association between a CTGF gene polymorphism and systemic sclerosis in a French population.

Objective. Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by chronic fibrosis of the skin and internal organs. Connective tissue growth factor (CTGF) is believed to be a primary mediator of chronic fibrosis. We assessed the possible association between 7 single-nucleotide polymorphisms (SNP) in the CTGF gene and scleroderma in a French population (registration number 2006/0182). Methods. We conducted a case-control study with 241 scleroderma patients and 269 controls. Seven SNP were genotyped using the TaqMan system. Univariate and multivariate analyses were performed. In silico electrophoretic mobility shift assay (EMSA), and reverse transcriptase polymerase chain reaction analyses were done to assess the effect of the SNP on CTGF gene expression. Results. The frequency of the rs9399005TT genotype was significantly lower in SSc patients than in controls. This association remained significant after adjustment for gender. An association was detected between the rs9399005 and the diffuse and limited cutaneous forms. Multivariate analysis between SSc patients and controls taking into account all 7 SNP and sex revealed that only sex and the rs9399005 SNP were associated with disease. DNA analysis by EMSA indicated that the T allele bound nuclear factors that were also bound by the C allele. The binding affinity was higher for the T allele. Analysis of the human database and experiments with human hepatocyte cell line indicated the existence of an alternative transcript containing the rs9399005 polymorphism in its 3’UTR region. In silico analysis indicated that this polymorphism may alter the structure of CTGF messenger RNA. Conclusion. These findings suggest that CTGF gene polymorphisms may contribute to susceptibility to scleroderma.

Specific xerostomia during Urbach-Wiethe disease.

We describe the case of a 59-year-old woman who had suffered from a typical Urbach-Wiethe disease since childhood and who complains of progressive mouth and ocular dryness since the age of 54 years. Xerostomia was severe with very poor salivation and was associated with a slight keratoconjunctivitis sicca. A specific lipoid proteinosis was evidenced in salivary glands (lower lip biopsy) with a PAS-positive hyalin-like deposit around vessels, capillaries and salivary gland canaliculi. An ultrastructural study showed the typical aspect of multilamination of the basal lamina of capillary vessels. Dysphonia and hoarseness are commonly found in Urbach-Wiethe disease, but, to our knowledge, a specific xerostomia has never been reported.

Polymyalgia rheumatica and mitochondrial myopathy: Clinicopathologic and biochemical studies in five cases

PURPOSE The coexistence of mitochondrial myopathy and polymyalgia rheumatica without giant cell arteritis is an interesting association. The frequency of this association was assessed in a prospective study. PATIENTS AND METHODS Muscle biopsy specimens were obtained from 15 patients with polymyalgia rheumatica. When ragged red fibers (RRF) were observed, histochemical, ultrastructural, and biochemical studies were performed. RESULTS In five cases, we found the typical appearance of mitochondrial myopathy, with the presence of numerous RRF. Histochemical and biochemical results confirmed these mitochondrial myopathies, showing miscellaneous deficiencies of mitochondrial respiratory chain enzymes. CONCLUSION Persistence of histologic and biochemical abnormalities after steroid treatment in two patients seems to indicate that a subclinical mitochondrial myopathy preceded polymyalgia rheumatica. How a mitochondrial myopathy could induce or facilitate the emergence of a polymyalgia rheumatica remains unknown.

Painful jaundice revealing Kawasaki disease in a young man

Abstract  Liver involvement is usually a minor manifestation of Kawasaki disease and includes hepatobiliary dysfunction or gallbladder hydrops. We describe here an unusual case of jaundice revealing an adult onset Kawasaki disease. An 18‐year‐old man presented with abdominal pain and jaundice associated with cholestasis as the initial manifestation of Kawasaki disease. Abdominal evaluation (ultrasonography and CT‐scan) did not find abnormality. Other signs typical of the Kawasaki disease occurred a few days later and permitted diagnosis. With aspirin and intravenous immunoglobulins, outcome was favorable without any cardiovascular complication. Our case suggests that Kawasaki disease should be added to the etiological list of painful febrile icterus in young patients.

Rapid Development of Multiple Squamous-Cell Carcinomas during Chronic Granulocytic Leukemia

We report a 65-year-old patient who presented a rapid eruption of keratoses on sun-exposed areas and an explosive transformation into several squamous-cell carcinomas, occurring during the accelerated phase of a chronic granulocytic leukemia. Clinical findings resembled those usually described in xeroderma pigmentosum. The role of immunosuppression, chemotherapy and possible genetic predisposition is discussed.

Livedo reticularis revealing a latent infective endocarditis due to Coxiella burnetti

We report the first case of livedo reticularis revealing a latent infective endocarditis due to Coxiella burnetti. The patient, a 54-year-old woman, also had chronic thrombocytopenia and mixed cryoglobulinemia. Chronic Q fever was confirmed by serodiagnosis and livedo regressed totally with doxycycline and hydroxychloroquine.