Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

The value of endoscopic ultrasound after bronchoscopy to diagnose thoracic sarcoidosis.

A clinicoradiological presentation of thoracic sarcoidosis requires histopathology in order to establish the diagnosis. Flexible bronchoscopy has a reasonable diagnostic yield and is the procedure of first choice for diagnosis. Endoscopic ultrasound (endoscopic ultrasound-guided fine needle aspiration/endobronchial ultrasound-guided transbronchial needle aspiration) can help in the diagnosis of sarcoidosis. An implementation strategy of endoscopic ultrasound for the diagnosis of sarcoidosis following negative flexible bronchoscopy results was examined prospectively in 15 clinics. A total of 137 patients (92 males; median age 43 yrs) were included, and sarcoidosis was found in 115 (84%). Alternative diagnoses were tuberculosis, lymphangitis carcinomatosa, pneumoconiosis and alveolitis. All patients were sent for flexible bronchoscopy, which was performed in 121 (88%), resulting in a definite diagnosis in 57 (42%). A total of 80 patients were sent for endoscopic ultrasound, which could be performed in 72 (90%), yielding a definite diagnosis in 47 (59%). Endoscopic ultrasound following negative flexible bronchoscopy avoided a surgical procedure in 47 out of 80 patients. The sensitivity of flexible bronchoscopy for sarcoidosis was 45% (95% confidence interval 35-54%), but 62% (50-72%) if biopsy specimens were taken. The sensitivity of endoscopic ultrasound following negative flexible bronchoscopy results was 71% (58-82%). With this strategy, 97 out of 115 (84% (76-90%)) of proven sarcoidosis was diagnosed using endoscopy. This large prospective implementation study (trial number NCT00888212; ClinicalTrials.gov) shows that endoscopic ultrasound is valuable for diagnosing sarcoidosis after negative flexible bronchoscopy results.

The missing link.

We present a case of a 28-year old woman who presented with bizarre wheezing breath sounds on expiration and dysphagia, with unexplained significant dilation of the esophagus mimicking achalasia finally leading to the diagnosis of a very small congenital tracheoesophageal fistula (TEF). Congenital TEF is usually detected shortly after birth and is typically accompanied by esophageal atresia. Congenital TEF without esophageal atresia (H-type fistula) can be missed in early life and diagnosis may be postponed until adulthood due to subtle symptoms. Diagnosis is usually based upon a combination of esophagoscopy, bronchoscopy, barium esophagography and CT-scan. The only clue can be the finding of a significant dilated aperistaltic esophagus, with subsequent more detailed CT reconstruction revealing a very tiny H-type TEF. It is important to raise the awareness of small H-type TEF as a possible cause of achalasia-like esophageal dilation in adulthood and of very unusual and bizarre wheezing breath sounds.

Wegener's granulomatosis presenting as a thyroid mass.

A 71-year-old patient was referred for suspected hyperthyroidism because of a 15-kg weight loss, suppressed thyroid stimulating hormone (TSH), and a 4-cm nodule in the left thyroid lobe. Both free T4 and T3 were normal. Antithyroglobulin, anti-TSH receptor and antimicrosomal antibodies were absent. Thyroid scintigraphy showed a cold nodule in the left thyroid lobe. CAT scan of the neck revealed a 4-cm inhomogeneous nodule at the left side. An elevated sedimentation rate suggested bacterial thyroiditis, localized Quervain thyroiditis, malignancy, and the fibrosing variant of Hashimoto's thyroiditis or Riedel's thyroiditis. A fine needle biopsy of the thyroid nodule showed no malignant cells but was inconclusive. A true cut biopsy demonstrated atypical inflammation and also failed to reveal the diagnosis. Therefore, the patient was admitted to the hospital for further work-up and was unexpectedly found to have nodular lesions in the lung on a chest X-ray. Additional blood analysis revealed a positive cytoplasmic ANCA-titer. After inconclusive peripheral lung biopsies, a left hemithyroidectomy and a very large video-assisted thoracoscopic lung biopsy were performed, both revealing extensive zones of necrosis surrounded by granulomatous foci pointing to the diagnosis of Wegener's granulomatosis (WG) disease. To our knowledge, this is the first report of a well-documented WG of the thyroid gland. Although extremely rare, WG should be included in differential diagnosis of inflammatory lesions of the thyroid gland.

Idiopathic hypereosinophilic syndrome-related pulmonary involvement diagnosed by bronchoalveolar lavage.

Patients with HES and pulmonary infiltrates may pose certain diagnostic problems as the infiltrates may be attributed to infection, infarction, congestive heart failure, or HES itself. We report an 87-year-old woman with idiopathic HES presenting with bibasal alveolar infiltrates. Differential cell count in BAL fluid yielded a very high percentage (73 percent) of eosinophils. Other authors previously mentioned the absence of eosinophils in the lavage fluid despite an important peripheral eosinophilia in a patient with the idiopathic HES but without HES-related pulmonary involvement. Thus, BAL fluid eosinophilia may suggest HES-related pulmonary involvement. Therefore, BAL might be an important diagnostic tool in the management of pulmonary infiltrates in idiopathic HES.

Recurring catamenial pneumothorax treated with a Gn-RH analogue.

We report a case of recurring catamenial pneumothorax with concurrent pelvic endometriosis. Thoracoscopy revealed a blue-like lesion on top of the dome of the right hemidiaphragm. Microscopic examination of biopsy specimens showed endometriosis. The patient was treated with a Gn-RH analogue and remains well without further evidence of pneumothorax after six months.

Unilateral segmental hyperhidrosis associated with pulmonary adenocarcinoma.

This is the report of a 38-year-old man with unilateral dermatomal hyperhidrosis documented by a starch-iodine technique; a subsequent diagnosis was made of a generalized pulmonary adenocarcinoma. The association of unilateral hyperhidrosis and a malignant tumor is reviewed.

Thoracoscopic findings in spontaneous pneumothorax in AIDS.

Six patients with the acquired immunodeficiency syndrome (AIDS) who suffered eight spontaneous pneumothoraces between January 1990 and January 1993 underwent videothoracoscopy. The predominant macroscopic findings, found in four patients on five occasions, were white-yellow nodules dispersed throughout the lung surface. In addition, in one patient, these lesions were associated with multiple small apical bullae and, in another, a large reddish nodule with several smaller white satellite nodules was noted on the parietal pleura. Methenamine silver stain of biopsy samples of both the visceral and parietal nodules in these patients showed the presence of Pneumocystis carinii. May-Grunwald-Giemsa stain of brushing samples of visceral lesions revealed P-carinii in two patients. In one of these patients, previously performed bronchoalveolar lavage (BAL) had not yielded P-carinii. On two occasions, the thoracoscopic findings were unremarkable, although in one of these patients, computed tomography (CT) had shown a large thick-walled cyst near the left hilum and BAL revealed P-carinii. Talc poudrage through the thoracoscopic cannula followed by chest tube drainage was performed in all patients and was successful in treating three of five with proved P-carinii pneumonia-related pneumothorax. The etiology of pneumothorax in AIDS and the diagnostic and therapeutic utility of videothoracoscopy in these patients are discussed.

SPECT findings in an unusual case of visual hallucinosis.

A 64-year-old right-handed man acutely developed elementary visual hallucinations (monochromatic, moving geometrical figures), visual illusions (distortion of the right side of faces) with achromatopsia and blurred vision restricted to the left visual hemi-field. CT of the brain before and after administration of contrast medium and a repeat examination 2 months later showed no abnormalities, while brain mapping (power analysis of EEG) demonstrated theta wave slowing of the curve over the posterior part of the right hemisphere. 99mTC HMPAO SPECT of the brain, however, demonstrated an area of definite focal hypoperfusion in the right occipito-temporal region. Echo-Doppler-duplex and continuous wave examination of the cervical arterial blood vessels disclosed bilateral discrete atheromatous plaques that did not affect the blood flow. Transoesophageal echocardiography demonstrated slight mitral valve insufficiency. Cerebral angiography showed an occlusion of the right posterior cerebral artery. After the visual hallucinations had subsided, SPECT showed partial normalization of the right occipito-temporal perfusion. In the absence of CT evidence for a structural lesion in the clinically suspected areas, only functional imaging revealed an obviously significant lesion. This case furthermore demonstrates that SPECT can contribute to the identification of the pathophysiology underlying visual hallucinosis.

Increase in serum myoglobin, creatine kinase, and free fatty acids, during recovery from a paralytic attack in hypokalemic periodic paralysis.

In a patient with hypokalemic periodic paralysis (HPP), recovery from a paralytic attack, coinciding with the restoration of plasma potassium, was associated with a rise in serum myoglobin (Mb) and creatine kinase (CK). The increase of muscle proteins in serum was preceded by an increase in serum free fatty acids (FFA). An increased permeability of the sarcolemma, caused by an accumulation of FFA within the muscle cell, might underly the reflux of potassium into the circulation. This might represent a mechanism by which the paralytic attacks in HPP terminate.

Immunogold-silver staining of cells recovered by bronchoalveolar lavage. A report of three cases demonstrating its value in the diagnosis of pulmonary involvement in hematologic malignancies.

BACKGROUND: The diagnosis of pulmonary involvement in hematologic malignancies (PHM) has traditionally necessitated large specimens (usually invasive or surgically obtained biopsies). The development of reliable immunocytologic identification techniques allows diagnosis on noninvasively obtained cellular material, including bronchoalveolar lavage (BAL) fluid. Since 1985, 12 such cases have been reported. CASES: Three cases of B-cell-related PHM were diagnosed by means of BAL fluid cellular analysis using the immunogold-silver staining technique. CONCLUSION: This is the first report showing immunogold-silver staining to be a reliable immunocytochemical identification technique for monoclonal B-cell populations recovered by BAL.

Echocardiographic diagnosis of platypnoea-orthodeoxia syndrome after blunt chest trauma.

Platypnea-orthodeoxia syndrome is a rare entity most often related to an interatrial right-to-left shunt. We report the case of a patient who developed platypnoea-orthodeoxia shortly after a blunt chest wall trauma. Definite diagnosis was obtained with transoesophageal echocardiography using contrast in upright and recumbent position. A Medline search did not reveal any other case report of the syndrome after chest wall injury.

Spontaneous pneumothorax in lymphomatoid granulomatosis.

Lymphomatoid granulomatosis is a unique form of pulmonary angiitis and granulomatosis characterized histologically by a necrotizing angiocentric and angiodestructive lymphoid infiltrate, which in most cases represents a proliferation of Epstein-Barr virus infected B-cells, with a prominent T-cell reaction. The most common radiographic findings in lymphoma-toid granulomatosis are multiple rounded mass densities, often suggestive of metastatic tumour. We report a case of spontaneous pneumothorax with bronchopleural fistula in a patient suffering from lymphomatoid granulomatosis.

Massive pleural effusion in systemic lupus erythematosus: thoracoscopic and immunohistological findings.

Small to moderate, bilateral pleural effusions are common during the course of systemic lupus erythematosus (SLE). These are related to several complications, particularly, congestive heart failure, nephrotic syndrome, pulmonary embolism or SLE itself. Thoracoscopy performed for a massive unilateral pleural effusion in a patient with SLE and inferior vena cava thrombosis revealed several small nodules on the visceral pleura. Immunofluorescence studies of biopsy samples showed immunoglobulin deposits confirming the lupus-related origin of the pleuritis.

Use of an Amplatzer Device for Endoscopic Closure of a Large Bronchopleural Fistula following Lobectomy for a Stage I Squamous Cell Carcinoma.

Bronchopleural fistulas can occur as a rare but severe complication after pulmonary resection. Established guidelines for the proper treatment of patients with bronchopleural fistulas do not exist. Apart from attempts to close the fistula, emphasis is placed on preventive measures, early treatment with antibiotics, drainage of the empyema and aggressive nutritional and rehabilitative support. For inoperable patients, endoscopic procedures are the only therapeutic option. Unfortunately, large (>8 mm) or central bronchopleural fistulas are usually not suitable for such endoscopic management. Recently, some groups have published a few case reports about a novel technique for the endobronchial closure of bronchopleural fistulas, using an Amplatzer device, originally designed for transcatheter closure of cardiac septal defects. We applied the same technique as a life-saving treatment in a ventilated patient who was considered inoperable due to a high oxygen need. The operation was successful. The patient could be weaned from ventilation and was eventually discharged from the hospital to a rehabilitation facility several weeks after the insertion of the device. Until now, endoscopic techniques have only been useful for the treatment of small, peripheral, bronchopleural fistulas and even then only as a bridge to surgery in high-risk surgical patients. In this case report, we demonstrate that the use of an Amplatzer device can expand the importance of endoscopic techniques in the treatment of bronchopleural fistulas. An Amplatzer device, for endobronchial closure, can indeed be administered for large and central bronchopleural fistulas. Moreover, it can be considered as a definite alternative to surgery in inoperable patients.

Treatment strategies for sarcoidosis.

Sarcoidosis is a multisystem disorder of unknown cause with a highly variable course. Corticosteroids are considered the standard agent for treatment, however there is no consensus about when and in whom therapy should be initiated, what dose should be given and for how long. There seems to be a limited benefit on chest radiographic findings, forced vital capacity and diffusing capacity. The evidence supporting the disease-modulating effect is limited. Cytotoxic agents are often used as steroid-sparing in patients requiring chronic therapy, however there are only little randomized controlled trials to support their use and side effects are common. Tumour necrosis factor-a is thought to be crucial in the development of the typical granulomas in sarcoidosis. Many case reports and case series suggest that specific therapy targeted against this cytokine is very effective. Despite these promising results, only limited evidence is found in multicenter randomized controlled trials.