Multidimensional analysis of clinical symptoms in patients with Fabry's disease.

AIM: Fabry's disease is an X-linked inherited lysosomal storage disorder caused by the deficient activity of alpha-galactosidase A. The interrelationships between clinical symptoms in Fabry patients have not yet been fully established. Using cluster and multivariate analysis, the aim of the study was to determine the relationships among clinical symptoms and organ involvement, and predictive clinical symptoms for disease severity. METHODS: Clinical data obtained from 108 French Fabry patients were retrospectively collected and analysed using multiple correspondence analysis and hierachical ascendant classification. Multivariate analysis was also performed to determine among clinical symptoms predictors for cardiac disease (HRT), renal involvement (KDN) and brain complication (STR). RESULTS: The cohort comprised 41 male patients (aged 28.9 ± 11.6 years) and 67 female patients (aged 40.4 ± 15.5 years). Three main clusters of clinical symptoms could be delineated, characterising disease progression: the first cluster grouped digestive disorders (found in 30% of the patients) and exercise intolerance (32%), the second, cluster dyshidrosis (47%), acroparesthesia (67%), angiokeratoma (44%) and cornea verticillata (54%), the third, cluster grouped KDN (30%), HRT (39%) and STR (25%) and hearing loss (44%). In univariate analysis, the patient age predicted HRT and KDN, dyshidrosis predicted HRT and STR, angiokeratoma predicted KDN and cornea verticilla and hearing loss predicted KDN, HRT and STR. In multivariate analysis, hearing loss and age were independent predictors of organ complication. CONCLUSION: Among the various interrelated clinical symptoms occurring in Fabry disease, patients with dyshidrosis and particularly hearing disorders appear to be at higher risk of organ complications.

Syndrome de Cogan.

"Typical" Cogan's syndrome is defined as a non-syphilitic interstitial keratitis associated with audio-vestibular resembling Ménière's disease with a 2-year maximum delay between these 2 organ impairment. Cogan syndrome is classified as "atypical" in the absence of interstitial keratitis and the presence of other inflammatory eye manifestations, an audio-vestibular impairment different from typical Menière-like disease, or a delay longer than 2 years between eye and audio-vestibular manifestations. Constitutional signs and large-vessel vasculitis is also possible, mostly affecting the thoracic aorta. The presence of acute-phase reactants is common, but no specific laboratory tests are available. The prognosis is dominated by the audio-vestibular impairment and in particular the risk of deafness, while other complications especially vascular complications being rare. Treatment with glucocorticoids is usually necessary and the combination to other immunosuppressive therapies or biological-targeted drugs needs to be determined.

[Rhabdomyolysis with major hypokalemia secondary to chronic glycyrrhizic acid ingestion]. / Rhabdomyolyse liée à une hypokaliémie profonde par intoxication chronique à la glycyrrhizine.

Intoxication by glycyrrhizic acid is a well-known cause of the apparent mineralocorticoid excess syndrome. It causes hypokalemia by inhibiting the enzyme 11-beta-hydroxysteroid dehydrogenase. We report a case of hypokalemic rhabdomyolysis secondary to chronic glycyrrhizic acid intoxication.

[Hypocomplementemic urticarial vasculitis]. / Vascularite urticarienne hypocomplémentémique.

Hypocomplementemic urticarial vasculitis is a rare disorder characterized by the presence of C1q precipitins associated with a syndrome of urticarial vasculitis, arthralgias, ocular inflammation and obstructive-lung disease. We report the case of a 48-year-old woman with hypocomplementemic urticarial vasculitis. Because of dependance to corticosteroids, cyclophosphamide-pulse therapy was started and resulted in significant clinical improvement. Mycophenolate mofetil was effective as maintenance therapy and resulted in complete resolution of rash, arthralgias, arthritis and uveitis, but had no effect on the obstructive-lung disease.

[Lupus profundus and myelopathy]. / Lupus profond et myélopathie.

BACKGROUND: We report a case of myelopathy during the course of lupus profundus that is unique to our knowledge. CASE-REPORT: A 29-year-old woman had lupus profundus since 1999, initially associated with thrombopenia (28,000 platelets/mm3) treated with corticosteroids for 6 months. Several nodular eruptions occurred from 1999 to 2004. Antinuclear antibodies were positive at 1/320 to 1/640 and complement C4 fraction was low. While being treated with hydroxychloroquine for a recent flare-up of nodular lesions of lupus profundus, she complained of paraesthesia of the abdominal wall and of the upper and lower limbs, suggestive of a medullary lesion. MRI disclosed an image of acute myelitis at the level of the second cervical vertebra. High doses of corticosteroids were promptly administered intravenously (methylprednisolone bolus) followed by oral prednisone and hydroxychloroquine. Six months later the patient was free of neurologic or cutaneous symptoms. DISCUSSION: In the literature, systemic signs are rarely associated with lupus profundus and myelitis has never been reported. Lupus myelitis is a vascular and/or demyelinating and usually segmental lesion of the spinal cord. Neurologic symptoms are those of acute rather than chronic or recurrent transverse myelitis. The prognosis is poor with frequent and severe functional sequelae. Treatment is mainly based on high-dose systemic corticotherapy alone or combined with cyclophosphamide. Our patient responded favourably to early methylprednisolone bolus followed by oral corticosteroids and antimalarial treatment. CONCLUSION: Lupus profundus is classically of benign course with only cutaneous involvement, but it may sometimes be a sign of systemic lupus and in rare cases may be associated with severe complications.

[Sarcoidosis presenting as an intrascrotal mass]. / Masse intrascrotale révélatrice d'une sarcoïdose.

INTRODUCTION: Sarcoidosis is a multisystem disorder that rarely involves the genitourinary tract. CASE: A 35-year-old man had intrascrotal extratesticular mass. Surgical exploration found noncaseating granulomatous inflammation. After the CT scan revealed mediastinal lymphadenopathy and splenomegaly, we diagnosed sarcoidosis. The patient responded rapidly to corticosteroids. DISCUSSION: Intrascrotal sarcoidosis is an unusual differential diagnosis for an intrascrotal mass. Histological testing is necessary to diagnose noncaseating granulomas. Other granulomatous diseases must be ruled out. Corticosteroid treatment is indicated only for symptomatic sarcoidosis with diffusion of granulomatous lesions and involvement of vital organs.

[Hypereosinophilic syndrome and orbital inflammatory pseudotumor]. / Syndrome hyperéosinophilique associé à une pseudo-tumeur inflammatoire orbitaire.

INTRODUCTION: Idiopathic hypereosinophilic syndrome is defined by the combination of persistent eosinophilia and evidence of tissue damage. It is a diagnosis of exclusion. CASE: We report the case of a 53-year-old man with idiopathic hypereosinophilic syndrome associated with an orbital inflammatory pseudotumor. Therapy with corticosteroids rapidly decreased the number of circulating eosinophiles; the orbital inflammatory pseudotumor regressed at the same time. DISCUSSION: This is the first report of idiopathic hypereosinophilic syndrome associated with an orbital inflammatory pseudotumor.

[Diagnostic approach of recurrent fevers of unknown origin in adults]. / Démarche diagnostique des fièvres récurrentes prolongées chez l'adulte.

Recurrent fever of unknown origin is probably the most difficult to diagnose subtype of fever of unknown origin. It represents between 18 and 42% of the cases in large series of patients with fever of unknown origin. The limited literature data do not allow one to construct a diagnostic algorithm. However, the diagnostic strategy is different from classic fever of unknown origin. The spectrum of causative disorders is different from continuous fever with less infections and tumors. Among systemic inflammatory diseases, adult-onset Still's disease is the most common cause. More than 50% of the cases remain unexplained. Hereditary recurrent fevers, the prototype of autoinflammatory diseases, are now more easily discuss in a young adult.

Curative non-surgical combined treatment of squamous cell carcinoma of the oesophagus.

Between April 1982 and June 1989, 65 patients (15 T1, 13 T2, 32 T3, 5 T4) with squamous cell carcinoma of the oesophagus were treated with a curative intent with multimodality combined treatment. A first course of 5-fluorouracil and cisplatin was given during work up, especially if NdYAG laser therapy was used. Irradiation was started 3-4 weeks after induction and two courses of concomitant chemotherapy were given during the radio therapy (aiming at 64 Gy over 7 weeks). Actuarial survival was 79.6% at 1, 36.7% at 3 and 26.7% at 5 years. 5 year survival rates were 56.3% for T1, 29.8% for T2 and 12.9% for T3. All T4 cases died within 16 months. Complete initial disease response was achieved in 76%. Tolerance was good. Thus patients with squamous cell carcinoma of the oesophagus can have long survival and may be cured with combined modality therapy. This treatment may be an alternative to radical surgery when there is a high risk of operative mortality.

[Autoimmunity and cancer: paraneoplastic neurological syndromes associated with small cell cancer]. / Auto-immunité et cancer: les syndromes neurologiques paranéoplasiques associés au cancer à petites cellules.

Paraneoplastic neurological syndromes are mostly associated with small cell lung cancer. Lambert-Eaton myasthenic syndrome appears to be caused by anti-presynaptic calcium channel antibodies. Calcium channels are also present in the cell membrane of small cell lung cancer, which may trigger the formation of anti-calcium channel antibodies. It is the most convincing argument in support of the auto-immune paraneoplastic theory, which refers to cross-antigenicity. Serum of patients with small cell carcinoma and cancer-associated retinopathy contains immunoglobulins against several antigens in the retinal and tumor cells. Patients with chronic intestinal pseudoobstruction (gastrointestinal neuropathy) associated with small cell lung cancer displayed circulating IgG antibodies reactive with neurons of myenteric plexus (anti-enteric neuronal antibodies). On the other hand, high levels of anti-neuronal antibodies (anti-Hu) have been found in the serum and cerebrospinal fluid of patients suffering from subacute encephalomyelitis (limbic encephalitis, cerebellar degeneration, sensory neuronopathy) associated with small cell lung cancer. The pathogenic role of the anti-neuronal antibody is not well established. Nevertheless, the finding of high titer antineuronal antibody in patients with a suggestive clinical syndrome is of great interest since it confirms the paraneoplastic syndrome and suggests the location of the primary tumor when the cancer is unknown.

[Cancer and primary humoral immunodeficiency]. / Cancer et déficit primitif de l'immunité humorale.

The occurrence of cancers in patients with primary humoral immunodeficiency syndrome (X-linked agammaglobulinemia, common variable immunodeficiency, IgA deficiency) is more than mere coincidence. An increased risk of non Hodgkin's lymphoma and gastric adenocarcinoma, particularly for patients with common variable immunodeficiency, is well established. A literature review is presented on this subject with analysis of case reports, prospective and retrospective studies, and data from the Minnesota Immunodeficiency Cancer Registry.

[Bronchiectasis following colectomy for hemorrhagic rectocolitis]. / Bronchectasies après colectomie pour rectocolite hémorragique.

Pulmonary disease is an uncommon extraintestinal manifestation of inflammatory bowel disease. We report the case of a patient in whom colectomy for ulcerative colitis was followed by development of bronchiectasis. A discussion of the relation between ulcerative colitis and bronchial disease is presented.

[Muscular sarcoidosis: apropos of a case]. / La sarcoïdose musculaire: à propos d'un cas.

We report the case of a 75-year old woman presenting sarcoid myopathy with pseudohypertrophy and skin involvement. Muscular biopsy confirmed the diagnosis of sarcoidosis. Symptomatic muscle involvement in sarcoidosis is rare. Three forms are described: myopathic, myositic and nodular. The relevance of imaging techniques is reviewed. Treatment is based on corticotherapy which is less efficient in myopathic form and in this case we had to use methotrexate with success.

[Necrobiotic xanthogranulomatosis: a cutaneous manifestation of a monoclonal IgM gammopathy]. / Xanthogranulomatose nécrobiotique: manifestation cutanée d'une IgM monoclonale.

INTRODUCTION: Necrobiotic xanthogranulomatosis is a rare cutaneous disorder usually associated with monoclonal gammopathy. Most frequently, cutaneous lesions involve the face (periorbital region) and the trunk, and are characterized by indurated xanthomatous plaques and nodules. EXEGESIS: We describe a patient presenting with necrobiotic xanthogranulomatosis that was unusual, as it was associated with IgM kappa monoclonal gammopathy of undetermined clinical significance and because no periorbital involvement was observed. CONCLUSIONS: Necrobiotic xanthogranulomatosis should be distinguished from other cutaneous manifestations associated with plasma cell dyscrasias, such as normolipemic plane xanthoma. It can be associated with IgM gammopathy.

[Myelopathy revealing lupus. Two cases and review of the literature]. / Myélopathie révélatrice d'un lupus. Deux observations et revue de la littérature.

INTRODUCTION: Myelopathy is a rare manifestation of systemic lupus erythematosus, occurring most often during the course of the disease. EXEGESIS: We report two cases of women with myelopathy as the first manifestation of systemic lupus erythematosus; both had an unusual course. We review the literature for previously reported cases. CONCLUSION: The clinical presentation of myelitis is heterogeneous. Usually, neurologic deficits evolve within a few hours (typically acute transverse myelitis) and outcome is usually poor. However, chronic or recurrent transverse myelitis has also been reported, including relapsing myelitis that resolved spontaneously. Myelopathy can be the first manifestation of the disease and this might be more common than initially thought. Magnetic resonance imaging (MRI) findings depend on the timing of the examination and the stage of the disease; the MRI may therefore be normal. An association with optic neuritis is frequently reported in the literature and differential diagnosis with multiple sclerosis may be difficult. Overlapping features between both diseases have been termed "lupoid sclerosis" and are actually classified as demyelinating syndromes associated with lupus. Myelopathy does not appear to be consistently associated with antiphospholipid antibodies, as has been previously suggested. The best treatment protocol has not been determined; however, in recent years, pulses of methylprednisolone and cyclophosphamide have gained acceptance by most authors.

[Constrictive bronchiolitis obliterans. Apropos of a case]. / Bronchiolite oblitérante constrictive. A propos d'un cas.

INTRODUCTION: Constrictive bronchiolitis obliterans is defined histologically as obliteration of the lumina of bronchioles by inflammatory tissue elements and progressive destruction of bronchioles, eventually replaced by fibrotic tissue. Most of the cases, which are not associated with either solid organ or bone marrow transplantation, occur in the development of rheumatoid arthritis. EXEGESIS: We present the case of a 73-year-old woman who developed severe constrictive bronchiolitis obliterans without readily identifiable cause, rapidly fatal despite corticosteroid therapy. The patient had antinuclear antibodies (titer 1/1024) and antiphospholipid antibodies, but there was no anti-DNA, anti-ENA or anti-beta 2GPI antibodies. Tests for rheumatoid factor were negative. Cryoglobulinemia was present (monoclonal IgM Kappa). CONCLUSION: In this case, constrictive bronchiolitis obliterans was associated with serologic abnormalities and cryoglobulinemia. However, were was no clinical evidence of connective tissue disease.

[Aortitis after G-CSF injections]. / Aortite après injections de G-CSF.

INTRODUCTION: Aortitis consists in aortic wall inflammation from infectious or non infectious cause. It may lead to aortic aneurysm with a risk of rupture, which is life-threatening and may justify surgical procedures. The cause of the aortitis is sometimes obscure. CASE REPORT: We report the case of a 55 years old woman who developed acute aortitis of the descending aorta after G-CSF (granulocyte-colony stimulating factor) injections for blood stem cells graft. No cause was found to the aortitis, the evolution was favorable after corticosteroid treatment, without aneurysm at six months. CONCLUSION: The present case rises the question of G-CSF (Neupogen responsibility in aortic lesions. Neutrophilic mediated diseases (Sweet's syndrome, pyoderma gangrenosum) and leukocytoclastic vasculitis were reported after G-CSF therapy. Neutrophils induced by G-CSF injections present functional abnormalities which may play a role in the pathogenesis of these diseases.

[Lambert-Eaton syndrome and small cell cancer. Etiopathogenic considerations apropos of 2 cases]. / Syndrome de Lambert-Eaton et cancer à pétites cellules. Considérations étiopathogéniques à propos de deux observations.

The authors report two cases of Lambert-Eaton myasthenic syndrome associated with small cell lung carcinoma. Following the observations, the clinical diagnosis of this syndrome is considered. We discuss the autoimmune pathogenesis and the relation between paraneoplastic syndrome and small cell cancer. This syndrome is caused by autoantibodies that block the voltage-dependent calcium channels at motor nerve terminals. Small cell carcinoma cells appear to express calcium channels, suggesting that autoantibody production may be triggered by tumor calcium channels determinants. The autoimmune paraneoplastic syndrome theory refers to cross-antigenicity.