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ObjectiveTo evaluate the efficacy and safety of golimumab to induce clinical remission in patients with very early, active peripheral spondyloarthritis (pSpA).MethodsClinical REmission in peripheral SPondyloArthritis is a monocentric study of golimumab treatment in patients with pSpA. All patients fulfilled the Assessment of SpondyloArthritis international Society classification criteria for pSpA, with a symptom duration ≤12 weeks. Patients were randomised 2:1 to receive golimumab 50 mg every 4 weeks or matching placebo for 24 weeks. The primary end point was the percentage of patients achieving clinical remission at week 24, defined as absence of arthritis, enthesitis and dactylitis. Secondary end points included joint and enthesis counts, patient-reported outcomes, erythrocyte sedimentation rate and C reactive protein. From week 12, non-responders were allowed to receive rescue medication with golimumab. Adverse events were recorded.Results60 patients were randomised with similar baseline characteristics. At week 24, a significantly higher percentage of patients receiving golimumab achieved clinical remission compared with placebo (75% (30/40) vs 20% (4/20); pConclusionsMarkedly high remission induction rates were noted with golimumab in very early pSpA. Of interest, in placebo-treated patients, very low spontaneous remission rates were observed.Trial registration numberNCT01426815; Results.

Tolosa-Hunt syndrome (THS) is a rare syndrome of painful ophthalmoplegia secondary to an idiopathic granulomatous inflammation affecting the cavernous sinus, superior orbital fissure or orbit. Pregnancy and pregnancy-related hormones have been identified as potential triggers. A 39-year-old gravida-2 para-1 woman with prior chronic intake of combined oral contraceptives (COC) suffered two episodes of painful ophthalmoplegia—the first event with spontaneous remission and the relapse occurring during pregnancy and with complete resolution following steroid treatment. MRI revealed a postinflammatory mass at the junction of the left orbital apex and anterior cavernous sinus, supporting the diagnosis of THS. To our knowledge, this is the first report of a THS relapse occurring during pregnancy following a chronic history of COC intake. This case adds to the growing evidence supporting the relationship between immune and hormonal factors that may be present during pregnancy and the disease pathogenesis of THS.

Anisometropia was recently shown to occur in 10% of infants diagnosed with dacryostenosis at a mean age of 1 year. The purpose of this study was to determine whether earlier (1 year) spontaneous resolution or probing decreases the risk of anisometropia in infants with dacryostenosis.The medical records of all patients diagnosed as infants with dacryostenosis at Mayo Clinic, Rochester, Minnesota, USA, from 1 January 1988 to 31 December 1992 were retrospectively reviewed. Of 662 consecutive infants diagnosed with dacryostenosis, 244 (36.9%) were subsequently examined in the ophthalmology department and included in the study. Each of the study patients was followed through to 30 June 2011. The main outcome measure was the rate of anisometropia (≥1 dioptre between the two eyes) among those who spontaneously resolved and those who underwent surgery.Among the 244 cases, 189 (77.5%) spontaneously resolved at a mean age of 4.5 months (range 0.3-35 months), and 55 (22.5%) underwent surgery at a mean age of 16 months (range 0-53 months). Anisometropia was diagnosed in 17 (9.0%) of the 189 who spontaneously resolved and in 2 (3.6%) of the 55 operated children (p=0.19). Although there was no significant trend, earlier resolution was associated with higher rates of anisometropia.Early spontaneous resolution of dacryostenosis was more likely to have a higher, not lower, rate of anisometropia than late spontaneous or surgical resolution. Further studies are warranted to clarify the relationship between infantile dacryostenosis and the development of hyperopic anisometropia.

Objectives: To test the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and disease activity score in 44 and 28 joints (DAS, DAS28) definitions of remission in early rheumatoid arthritis (RA), against disability and ultrasound-detectable synovitis. Methods: In an observational study of early RA patients, remission rates were determined and compared in 166 patients. The remission definitions included the simplified disease activity index (SDAI≤3.3), ACR/EULAR (categorical), DAS28 (

OBJECTIVE: An epidemic of acute hepatitis C virus (HCV) infection in HIV-positive men-who-have-sex-with-men (MSM) is emerging in Europe, Australia and the USA. The aim of this study was to characterise the natural history of primary HCV in this setting and to assess host and viral factors which predict spontaneous clearance. METHODS: This prospective longitudinal cohort study was carried out in 112 HIV-positive patients who were followed in a single centre (the St Mary's Acute HCV Cohort). Plasma and peripheral blood mononuclear cells (PBMCs) were obtained at monthly intervals for 3 months and at 3-monthly intervals thereafter for a median of 45 months (IQR = 29-69 months). The primary end point was spontaneous clearance of HCV. Cox regression was used to assess the impact of clinical and virological variables on outcome, including liver function, CD4 count, rate of HCV RNA decline, T cell response and clonal sequence evolution within the HCV E2 envelope gene. RESULTS: 15% of patients cleared HCV spontaneously, while 85% progressed towards chronicity. The latter group included a significant proportion of 'fluctuating' progressors (37.5%), in whom a fall followed by a rise (>1 log₁₀) in viraemia was observed. This was associated with superinfection with new HCV strains and partially effective T cell responses. Spontaneous clearance was strongly associated with a 2.2 log₁₀ viral load drop within 100 days of infection (HR = 1.78; p < 0.0001), elevated bilirubin (≥ 40 μmol/l; HR = 5.04; p = 0.006), elevated alanine aminotransferase (ALT; ≥ 1000 IU/ml; HR = 2.62; p = 0.048) and baseline CD4 count ≥ 650 × 10⁶/l (HR = 2.66; p = 0.045), and only occurred in patients with genotype 1 infection. Evolution to spontaneous clearance occurred in patients with low viral diversity in the presence of an early multispecific T cell response. CONCLUSIONS: Spontaneous clearance of acute HCV in HIV-positive men can be predicted by a rapid decline in viral load, high CD4 count, elevated bilirubin and ALT, and is associated with low viral diversity and strong T cell responses.

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma (KA), characterised by a progressively expanding tumour with a lack of spontaneous remission and significant scarring. KCM has been reported previously in less than 50 cases worldwide. We present the case of a large solitary KCM on the right shin of a 71-year-old woman. This was treated successfully with oral acitretin for 16 months with sustained remission at 24 months. Our case provides further supporting evidence for acitretin as a useful treatment for KCM to induce remission, prevent extensive surgery and minimise destructive scarring.

Perspective on the review by Bose and Laughon (see page 498) Patent ductus arteriosus (PDA) is common problem, with rates of 40–55% in babies born less than 29 weeks’ gestation,1 2 yet decisions related to management remain highly controversial. Despite numerous studies on the topic there remains uncertainty with respect to diagnosis, assignment of clinical importance, whether treatment is indicated and if so the preferred treatment modality. The most fundamental question remains unanswered: does a PDA cause acute physiological or clinical change that either acutely or chronically leads to organ damage, which further leads to important neonatal morbidities? Put simply is the PDA an “innocent bystander” or is it pathological to the extent that early detection and intervention is warranted to prevent neonatal morbidity? It is physiologically plausible that a major systemic to pulmonary (left-to-right) shunt can lead to considerable postnatal morbidities in extremely low birthweight (ELBW) infants, either from pulmonary overcirculation (eg, chronic lung disease (CLD)) and/or systemic hypoperfusion (eg, necrotising enterocolitis (NEC), acute renal impairment).3 The lack of evidence supporting causality,4 5 failure of medical treatment in some cases1 and the inherent risks of medical6 7 or surgical treatment options8 has led some investigators to question whether intervention is necessary. In contrast, studies of prophylactic indometacin show reduced rates of PDA ligation, early major pulmonary haemorrhage and serious (grades III–IV) intracranial haemorrhage.9 10 This strategy does, however, expose 40% of babies, in whom spontaneous PDA closure would have occurred, to any adverse effects of treatment. The medical community is becoming increasingly divided on the question of treatment of the PDA. Laughon and Bose highlight some important gaps in our knowledge with respect to therapeutic intervention.11 They emphasise that recent trials of non-steroidal anti-inflammatory agents have not led to any …

In the last decade invasive electrophysiological studies (EPS) and radiofrequency catheter ablation (RFCA) have become progressively common, driven predominantly by high success and low complication rates, coupled with the inefficacy and side effects of many antiarrhythmic agents. As our understanding of different arrhythmia mechanisms and successful ablative strategies has advanced, RFCA has been applied to increasingly complex substrates and broader clinical indications. Two such examples are young adults with native or surgically repaired congenital heart disease and children with structurally normal hearts. In such situations arrhythmia management should be performed on an individualised basis, considering the potential risks and benefits of different strategies. In young children the natural history of the arrhythmia, the effects of medication and potential life-threatening complications must all be weighed against the risk of RFCA. In adults with congenital heart disease, arrhythmia management must be closely coordinated between electrophysiologist, cardiologist and cardiac surgeon to optimise haemodynamic performance, potentially performed in conjunction with surgery or other percutaneous interventions. This article aims to review the current indications for EPS and RFCA in both groups of patients, specifically focusing on areas of ongoing interest and debate. ### Arrhythmia mechanism and presentation The vast majority of supraventricular tachycardias (SVT) seen in children without congenital cardiac anomalies are atrioventricular reentry tachycardia (AVRT) facilitated by an accessory pathway (AP), atrioventricular nodal reentry tachycardia (AVNRT) and focal atrial tachycardia (FAT). Presentation of AVRT is most common in the neonatal and infant groups, with the vast majority free from symptomatic arrhythmia by the end of the first year of life, although recurrence in later childhood or adolescence is well recognised. Spontaneous remission in those older than 5 years of age at presentation is much less common.1 Conversely AVNRT is rare in early childhood, becoming more frequent with increasing age, mirroring patterns seen in adult practice. Other less common …

Objectives: The evolutionary pattern of spontaneous recovery from acute neglect was studied by assessing cognitive deficits and motor impairments. Detailed lesion reconstruction was also performed to correlate the presence of and recovery from neglect to neural substrates. Methods: A consecutive series of right brain-damaged (RBD) patients with and without neglect underwent weekly tests in the acute phase of the illness. The battery assessed neglect deficits, neglect-related deficits, and motor impairment. Age-matched normal subjects were also investigated to ascertain the presence of non lateralised attentional deficits. Some neglect patients were also available for later investigation during the chronic phase of their illness. Results: Partial recovery of neglect deficits was observed at the end of the acute period and during the chronic phase. Spatial attention was impaired in acute neglect patients, while non spatial attentional deficits were present in RBD patients with and without acute neglect. A strong association was found between acute neglect and fronto-parietal lesions. Similar lesions were associated with neglect persistence. In the chronic stage, neglect recovery was paralleled by improved motor control of the contralesional upper limb, thus emphasising that neglect is a negative prognostic factor in motor functional recovery. Conclusions: These findings show that spatial attention deficits partially improve during the acute phase of the disease in less than half the patients investigated. There was an improvement in left visuospatial neglect at a later, chronic stage of the disease, but this recovery was not complete.

Better information of the natural history of epilepsy has important implications for understanding the underlying neurobiology, evaluating treatment strategies, and planning healthcare resources. The traditional pessimistic view has been dispelled by results from modern community based prospective studies, showing that over 60% of newly diagnosed patients will enter remission upon treatment. Recent outcome studies suggest that medical intractability may be predicted after failure of two antiepileptic drugs. Poor prognostic factors include a high initial seizure density, symptomatic aetiology, and presence of structural cerebral abnormalities, all of which can be identified early on. Among patients who have entered remission, many will remain seizure-free after antiepileptic drug treatment is withdrawn, suggesting that the underlying seizure generating factor has remitted. Whether some of these patients have entered remission "spontaneously" is contentious because, with effective pharmacotherapy for epilepsy in use for over 100 years, the natural history of untreated epilepsy is largely unknown. Circumstantial evidence, mostly arising from resource poor countries where antiepileptic drug treatment is not readily available, indicates that spontaneous remission may occur in up to 30% of cases. Observations from these complementary sources suggest that, at the population level, prognosis of newly diagnosed epilepsy may be broadly categorised into three groups: remission without treatment, remission with treatment only, and persistent seizures despite treatment. As understanding of the prognostic factors improves, the potential of a "prognostic group specific" management approach should be explored so that effective treatments may be used in a more rational and targeted fashion.

Gestational trophoblastic disease (GTD) represents a spectrum of histologically distinct entities including molar pregnancy and choriocarcinoma. The incidence of GTD varies in different parts of the world with high incidences in countries like Japan (2/1000 pregnancies). With the advent of sensitive assays for detection of serum β human chorionic gonadotrophin (HCG) and ultrasound, GTD can now be detected earlier in pregnancy. To date no studies have been reported from South Africa regarding the epidemiology, management, and outcome of patients with GTD. This study was a retrospective audit based on 112 patients with GTD treated at King Edward VIII Hospital, Durban, South Africa. Clinical records of patients were reviewed with regards to presentation, investigation, management and outcome. Of 112 patients, there were 78 patients (70%) with hydatidiform mole and 34 patients (30%) with choriocarcinoma. The mean age of patients was 28.5 years (SD 8.1 years). The majority of patients were Black females (94.6%) while 4.4% were Asian and 1% Coloured females. The most common presenting symptom was vaginal bleeding (93.8%). There were 74 patients (66.7%) who had a previous normal term pregnancy and only two patients (1.8%) had previous molar pregnancies. Suction curettage was the main treatment modality for patients with molar pregnancy while choriocarcinoma was treated primarily with chemotherapy. A total of 72 percent of patients with molar pregnancy and 28 percent with choriocarcinoma had complete remission after initial treatment. Twelve patients died during the course of treatment mainly due to late presentation and advanced metastatic disease. Complete cure was achieved in 89% of patients. Age, parity, previous history, initial uterine size, presence of theca-lutein cysts, and initial βHCG concentration was not found to be prognostic for persistent trophoblastic disease. In the present study, the incidence of molar pregnancy and choriocarcinoma was 1.2/1000 and 0.5/1000 deliveries, respectively. This is much lower than those quoted from countries such as Japan. However, the incidence quoted from our study may be overestimated as this was a hospital-based study and most of the uncomplicated deliveries occur in referring centers. Only 20% of patients in this study were above the age of 35 years with a mean age of 28.5 years. The majority of patients were of Black African ethnic origin mainly due to the fact that our hospital is a referral center for Black patients. Similar to other studies, the majority of patients with molar pregnancy were treated with suction curettage while the majority of patients with choriocarcinoma were treated with chemotherapy. Overall, spontaneous remission was achieved in 60% of patients with molar pregnancy and an overall complete cure was achieved in 89% of patients.

Patients with hemispatial neglect following right hemisphere brain damage fail to spontaneously orient towards or respond to contralesional stimuli.1 The diagnosis and longitudinal assessment of the syndrome is not always straightforward. This is mainly due to two reasons: the heterogeneity of the syndrome and inter-individual differences in the time course of recovery from the disorder. The neglect syndrome affects various cognitive components across patients, and one patient may show neglect on certain tasks but not on others.1 ,2 Because there is no single test able to detect neglect in all patients, a battery of several paper-and-pencil tests is usually required.1 ,3 However, little is known about their use as a tool for longitudinal assessments. This is of high clinical importance as repeat assessments are necessary to monitor changes in neglect severity related to spontaneous remission or a specific treatment. If a test per se is not ‘stable’, the variation in test results over repeated sessions may simply reflect low test–retest reliability and not the actual change of the underlying disorder. We therefore investigated the test–retest reliability of three …

Unanswered questions Autoimmune pancreatitis (AIP) is part of a systemic fibro-inflammatory disease that can involve multiple organs which characteristically have a lymphoplasmacytic infiltrate rich in IgG4-positive cells. IgG4-related systemic disease (ISD) has been proposed by Kamisawa et al as the umbrella term to describe this multi-organ disease.1 Although the fibrosis in ISD can often lead to damage and even destruction of the involved organ, the inflammatory process typically responds to steroid treatment. However, the resolution of the inflammatory process in ISD may occur spontaneously without steroid treatment, especially in AIP.2 3 The effect of steroid treatment on the natural history of AIP is not known as it is only recently that large series of AIP are being reported. In this issue of Gut ( page 1719 ), Hirano et al 4 report the results of a retrospective review of 42 AIP patients of whom 19 were treated with steroids. The authors’ goal was to determine the effect of steroids on subsequent disease relapse by comparing “unfavourable events” in steroid treated patients with those in historical controls presenting before 2003 who did not receive steroids. “Unfavourable events” included the development of obstructive jaundice related to distal biliary stricture, sclerosing cholangitis with elevated liver enzymes, growing pancreatic pseudocyst or other extra pancreatic lesions that required treatment (retroperitoneal fibrosis, interstitial nephritis, sialoadenitis). “Unfavourable events” were less in the steroid treated group compared to controls (32% vs 70%, p _ 0.01). The authors conclude that steroid treatment could reduce subsequent disease relapse and thus recommend the early introduction of steroids. When discussing treatment in AIP, it is important to use specific terms that help identify treatment goals and responses. Remission refers to the resolution of disease-related symptoms and radiological abnormalities, whether spontaneously (spontaneous remission) or with steroids (steroid-induced remission), keeping in mind that in …

OBJECTIVES—To review the outcome measures commonly used in phase III treatment trials of relapsing-remitting multiple sclerosis and to introduce a method of data analysis which is clinically appropriate for the often reversible disability in this type of multiple sclerosis. METHODS—The conventional end point measures for disability change are inadequate and potentially misleading. Those using the disability difference between study entry and completion do not take into account serial data or disease fluctuations. Rigid definitions of "disease progression" based on two measurements of change in disability several months apart, do not assess worsening after the defined "end point", nor the significant proportion of erroneous "treatment failures" which result from subsequent recovery from relapses that outlast the end point. Assessing attacks merely by counting their frequency ignores the variation in magnitude and duration. These problems can be largely circumvented by integrating the area under a disability-time curve (AUC), a technique which utilises all serial measurements at scheduled visits and during relapses to summarise the total neurological dysfunction experienced by an individual patient on any particular clinical scale during a study period. CONCLUSIONS—The "summary measure" statistic AUC incorporates both transient and progressive disability into an overall estimate of the dysfunction that was experienced by a patient during a period of time. It is statistically more powerful and clinically more meaningful than conventional methods of assessing disability changes, particularly for trials which are too short to expect to disclose major treatment effects on irreversible disability in patients with a fluctuating disease.

OBJECTIVES To examine cognitive and neurological changes and their relation to brain pathology in patients with multiple sclerosis during acute relapse. METHODS Thirteen patients with multiple sclerosis were examined with a battery of neuropsychological tests during acute relapse and six weeks later. Their performance was compared with the performance of 10 controls matched for age and premorbid IQ. Gadolinium (Gd) enhanced MRI was also performed in patients on both occasions. RESULTS The patients with multiple sclerosis performed significantly worse than controls on most tests of attention and memory during acute relapse and in remission. At follow up there was a significant or trend of improvement in performance on some tests of attention for patients in whom the Gd enhanced lesion load had decreased. In this subgroup of patients, their improvement also correlated significantly with the reduction in acute lesion load. CONCLUSIONS The findings suggest that certain neuropsychological deficits detected during an acute relapse may be reversible, particularly in patients who initially have mild cognitive impairment.

A case of pathologically confirmed progressive multifocal leucoencephalopathy presenting with unilateral parkinsonism and cognitive decline that significantly improved over a 12‐month period without any treatment is described. The patient had a background of chronic lymphocytic leukaemia, but had been in complete remission for 4 years at the time of diagnosis. This case is highly unusual not only in terms of the mode of clinical presentation in an apparently immunocompetent patient but also in that the patient spontaneously improved without any intervention. Progressive multifocal leucoencephalopathy should therefore be considered in the differential diagnosis of movement disorders developing in patients with a history of lymphoproliferative disease, even if they are in remission. Furthermore, such cases may not always require treatment, as the patient's immune system may overcome the viral disease process with spontaneous resolution of their neurological disorder.

OBJECTIVE--To assess the usefulness of serial cord MRI in patients with progressive multiple sclerosis. METHODS--Monthly MRI of the brain and spinal cord with and without gadolinium enhancement was carried out in 19 patients with progressive multiple sclerosis (10 primary progressive, nine secondary progressive) over the course of one year. RESULTS--During this period there were 132 active lesions in the brain and only six in the cord. One hundred and twelve (85%) active brain lesions occurred in the secondary progressive group; three new cord lesions occurred in each group. In the secondary progressive group MRI activity was high in patients who had superimposed relapses, whereas in those who progressed without relapse and in the primary progressive group it was low. Cross sectional areas of the cord decreased at the C5 level in both groups, implying progressive atrophy of fibre tracts. There was no relation between either brain or cord MRI activity and change in disability over the study period. CONCLUSIONS--Although the detection of new lesions by frequent cord imaging using current technology has little role in the monitoring of disease activity in progressive multiple sclerosis, the serial measurement of cord cross sectional area may be important. There is also evidence to suggest that the mechanism underlying irreversible disability in patients with progressive multiple sclerosis may be different in patients who continue to relapse than in those who do not.

A third of adults who had had asthma diagnosed in the previous five years showed no evidence of current asthma, a study in JAMA has found.1 The study authors said that this could be due to spontaneous remission or initial misdiagnosis. They recommended that doctors review patients to see whether treatment can be stepped down or discontinued and that they order objective tests such as spirometry before and after bronchodilator administration to avoid unnecessary treatment or …

Dear Editor, I read with interest the article by Ajeganova et al 1 reporting disease-modifying antirheumatic drug (DMARD) free sustained remission in rheumatoid arthritis (RA) as an increasingly achievable outcome with subsidence of disease symptoms. The conclusion of their study was that more intensive treatment strategies increased the chance for DMARD-free sustained remission, indicating that RA chronicity can be influenced. Of note, ‘Patients who achieved DMARD-free sustained remission, compared with those who did not, were less often anti-citrullinated protein antibodies (ACPA) or rheumatoid factor (RF) positive (18% vs 62%, and 31% vs 65%, both p≤0.001) and had shorter symptom duration …

Introduction Cerebral amyloid angiopathy-related inflammation (CAA-I) is a rare neurological condition with significant morbidity and mortality. Here we present a case of CAA-I that demonstrates its varied clinical course. Case A 76-year-old woman presented with subacute headache. Further assessment revealed mild cognitive impairment and left quadrantanopia. Right hemisphere hyperdensity was observed on MRI FLAIR sequence suggesting inflammatory amyloid. Steroid treatment was commenced for probable CAA-I but was eventually discontinued due to severe side effects. Clinical improvement was noted and corroborated by re-imaging which demonstrated complete resolution of the inflammatory changes. Cognitive decline occurred again 8 months later. MRI showed right hemisphere hyperdensity with microbleeds on gradient echo, in keeping with a CAA-I relapse. She underwent brain biopsy which confirmed underlying CAA although no inflammatory cells were seen. Remarkably she subsequently improved clinically and radiologically without having undergone any medical treatment suggesting a spontaneous remission of her CAA-I. Discussion Despite criteria for non-invasive diagnosis of CAA-I, using clinical features and radiology (Chung criteria), brain biopsy is still sometimes required to make the diagnosis. Successful treatment can be achieved, particularly with corticosteroids. Our case not only highlights how patients can relapse off of treatment but also that spontaneous remission is possible.

Recently new classification criteria have been developed for axial spondyloarthritis (SpA) covering both patients who already show radiographic evidence of structrual damage in the sacroilac joints (or spine), termed radiographic axila SpA (or using the older term: ankylosing spondylitis (AS)) and patients in the earlier phase without radiographic evidence of structural damage in the bone, termed non-radiographic (nr) axial SpA. There is general agreement that these two stages represent a continuum of the same disease and that preferentially the term axial SpA should be used. Both EMA and FDA have raised questions about the natural course of the earlier stage (nr-axSpA), the potential rate of spontaneous remission and the possibilty of overtreatment with biologcs in these patients. However, the EMA has accepted that there was an unmet need for treatment with TNF-blockers of these patients if they fail conventional therapy, which resulted in an approval for TNF-blockers for nr-axSpA - in addition to patients with AS - in the EU, if they have objective signs of inflammation such as positive CRP and/or active bone inflammation on MRI, and many other countries but not the US. The EMA has demanded post-approval studies from the TNF-blocker companies investigating what happens if the drug is stopped (or the dosage reduced) in patients who are reaching remission. These studies are ongoing and will deliver sufficient informations whether overtreatment might occur in these patients. In contrast, the FDA is asking for further phase 3 trials which include a placebo-controlled phase over 12 months. Such a study design would be very difficult to be conducted in EU countries – withholding an effective drug up to 12 months from active patients. But the different apporaches used by the two agencies also reflect that European rheumatologists have been much more familiar over the last decades with this early phase of axSpA compared to US rheumatologists. It is hoped that the results of the ongoing trials - in Europe, US and other parts oft he world – will result in a worldwide acceptance of the axial SpA concept and of the need to offer adaequate treatment to all axial SpA patients in their active phase. Disclosure of Interest None declared

Glossopharyngeal neuralgia is a rare pain syndrome presenting with paroxysms of pain in the region of the glossopharyngeal nerve. Even more uncommon is the association between glossopharyngeal neuralgia and cardiac syncope. In these patients, the cardiovascular consequences may include bradycardia, hypotension and cardiac arrest. We describe the case of a 40-year-old patient who presented with this rare association of glossopharyngeal neuralgia and syncope. Multiple pauses including one lasting 14 s were noted on ambulatory ECG monitoring. In this case, the patient declined pharmacological treatment with carbamazepine or with permanent pacing and so far has been in remission from symptoms for 3 months.

Zoledronic acid is widely used for the treatment of various skeletal disorders. While acute phase reactions are commonly seen, hypocalcaemia, femoral shaft fractures, osteonecrosis of the jaw and renal failure are rare. Two cases of fatal thrombocytopaenic purpura have been reported following zoledronic acid infusion. We report a case of non-fatal thrombocytopaenia with spontaneous recovery. A 70-year woman with osteoporosis participated in a research study. Complete blood and platelet counts prior to zoledronic acid infusion were normal (138 000/µL), but had declined slightly from 185 000/µL 2 years ago. One year after the first zoledronic acid infusion, her platelet count declined to 50 000/µL without any clinical manifestations, and rose slowly returning to normal (156 000/µL) over the next 1 year. Extensive evaluation did not reveal any specific abnormalities, and the pathogenesis of her transient severe thrombocytopaenia after two infusions of zoledronic acid remains unclear.

A 14 year old girl presented with severe tricuspid regurgitation after she was diagnosed with "transient tricuspid regurgitation of the newborn". In the neonatal period she had presented with severe tricuspid regurgitation without an obvious underlying anatomical cause. This spontaneously regressed during the first months of life. She was dismissed from follow up at the age of 5 years after complete normalisation of the clinical and echocardiographic examination. The subsequent evolution and management of the patient, as well as the possible pathogenesis responsible for the unusual clinical course, is discussed. This case stresses the importance of long term follow up of patients with transient tricuspid regurgitation. Keywords: neonatal cardiomyopathy; regurgitation; tricuspid valve

A 10-day-old Caucasian boy presented at the emergency department with a history of excessive sweating in the last 3 days, especially during feedings (figure 1). Figure 1 Unilateral hyperhidrosis, requiring multiple changes of clothes. The red line illustrates the body's midline. On presentation, the patient was systemically well without fever or irritability. A distinct unilateral transient flushing and hyperhidrosis of the trunk became apparent only when the baby was suddenly laid down for …

We report a case of spontaneous resolution of a recurrent axillary cystic hygroma in a 4-year-old boy. He presented with a 1-year history of a cystic lump in the left axilla, which intermittently changed in size. Ultrasound suggested it was a lipoma, with raised suspicions of vascular malformation. Scans were discussed in a multidisciplinary meeting and provisional diagnosis of lymphocele or slow flow lymphovascular malformation was made. It was surgically excised and histology confirmed the lesion to be a cystic hygroma. However, it recurred within 3 weeks. The patient was booked for aspiration and treatment with sclerotic agent OK 432. He developed acute infection in the cystic hygroma a week before surgical intervention and was treated with antibiotics for 5 days by his general practitioner. Acute infection led to complete spontaneous resolution of the cystic hygroma within a week. There are no other reported cases in which recurrent cystic hygroma has resolved after a week of acute infection.

Although neonatal renal medullary hyperechogenicity can occur in a variety of pathological conditions, it has been reported to occur transiently with or without renal abnormalities in term as well as in preterm neonates. Variably described in the literature as Tamm-Horsfall nephropathy, or stasis nephropathy, the pathogenesis is unknown, but has an excellent prognosis. The authors describe a 3-day-old neonate with transient renal medullary hyperechogenicity, with no other abnormalities, which resolved within 2 weeks.

See article on page 570 Hepatitis C virus (HCV) is a major public health problem around the world, with a prevalence ranging from 0.5 to 2% in most developed countries. After acute infection, spontaneous remission is a rare event. Although long term consequences of HCV infection are controversial, there is a consensus emerging that HCV infection is a progressive disease resulting in liver failure in some but probably in a minority of infected individuals. Patients who lack biochemical evidence of liver injury may be an important subset with a “more benign” natural history.1 In the rare situation where spontaneous cure occurs after acute infection, aminotransferase activities normalise and HCV RNA becomes undetectable in serum. By contrast, the serological profile shows minor modifications with time. With chronicity, serum HCV RNA remains detectable in the vast majority of individuals. Undetectable HCV RNA in serum in patients with abnormal liver enzymes may be related to low viraemia, be under the limit of detection of virological assays, or be due to a fluctuating course. In anti-HCV positive individuals with normal enzymes, however, the lack of serum HCV RNA has been interpreted as complete cure of the infection. However, the study by Haydon et al in this issue (see page 570) challenges this interpretation. These investigators have documented HCV RNA in liver in the majority of patients with exposure to HCV (confirmed by RIBA 3) whether or not virus was detectable in serum, suggesting that residual HCV infection occurs not only among those individuals with abnormal liver enzymes but also among those considered to have “resolved infection”. Although a high correlation exists between third generation assays and HCV RNA in serum,2 a small subgroup of patients remains, focused on in this study, which are …

A 37 year old patient with chronic active hepatitis progressing to cirrhosis presented with increasing breathlessness and was found to be hypoxic with finger clubbing. A progressive exercise study with measurement of oxygen saturation (SaO2) showed abnormally high ventilation and desaturation to 81% at 100 W. Serial studies over nearly two years showed, first, deterioration, then improvement with lower ventilation and higher saturation levels at all work loads. This could not be correlated with any change in treatment with azathioprine, prednisolone, or propranolol.

Spontaneous closure of a dural arteriovenous fistula (dAVF) is a rare condition and only a few cases have been reported since its first description in 1976. We report delayed and progressive spontaneous closure of a dAVF after massive intracerebral hemorrhage documented by angiographic studies before and after bleeding. To our knowledge, this is the first report to document gradual closure of a dAVF by serial angiographic studies. The mechanism of spontaneous closure of dAVFs has not been fully elucidated. We suggest different factors for consideration from previously published data and show how each of these factors can influence the others.

Transient osteoporosis is a rare musculoskeletal condition that has been reported in pregnant women and middle-aged men. We present a bilateral case in a young man. A 20-year-old man presented with spontaneous onset left hip pain. Investigations excluded other differential diagnoses such as infection or fracture. The pain resolved completely; 6 months later the patient presented with a similar episode of pain in the contralateral hip. This also resolved spontaneously. Doctors need to be aware of the possibility of spontaneous onset musculoskeletal pain due to transient osteoporosis occurring in young men. The typical presentation is of spontaneous onset progressive pain, often affecting the hip. Other pathology must be excluded. The investigation of choice is MRI, and the treatment is simple analgesia.

Background Undifferentiated arthritis (UA) is defined as an inflammatory arthritis in which no definitive diagnosis can be made. The prognosis of patients with UA may vary from spontaneous remission, to severe defined inflammatory joint disease. Patients UA poses a challenging problem to the rheumatologist. It is important to identify patients who will develop a persistent and/or erosive disease because early treatment might offer an effective means to slow disease progression. Objectives To describe the outcome of patients with UA after 30 months of follow up. Methods Design retrospective (2006 - 2011) in an academic tertiary hospital with a reference area of 850,000 inhabitants. We reviewed the medical records of patients with “undifferentiated arthritis” from the database of rheumatology Department. We reviewed the pattern of involvement at the onset of the disease and final diagnosis in December 2013. Results A hundred and fifty four patients were included. The involvement, at the beginning of the disease was: 36 (23.3%) monoarticular, 71 (46.1%) oligoarticular and 47 (30.5%) polyarticular. During follow-up, it was observed that 30 (19.5%) patients went into remission spontaneously, 57 (64.9%) evolved to a defined inflammatory joint disease and 67 (43.5%) continued under the diagnosis of undifferentiated arthritis. Among those patients were a definite inflammatory joint disease was established: 38 (66.6%) continued follow up controls, 16 (28%) discontinued the follow-up and 3 (5.3%) were discharged. A progression to extended polyarthitis was observed in 3 patients with an oligoarticular pattern. Four patients with monoarthitis developed oligoarthritis. The knee was the most commonly involved joint (58.3%). Conclusions The most common pattern of joint involvement in UA is oligoarticular. Furthermore half of patients with UA went into remission. Patients with a monoarticular pattern had a greater chance of spontaneous remission compared with patients with oligo and polyarticular involvement. The frequency of follow up was also significantly higher in patients with definite inflammatory joint disease compared with patients with persistent UA (66.6% versus 47.7%). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2933

Mr Paul Harder, a 66 year-old right-handed male architect was born after an uneventful pregnancy and suffered no childhood diseases before developing epilepsy at age 7 years. Initially, seizures consisted of episodes of the right hand and arm shaking. He was treated with numerous antiepileptic drugs throughout childhood and adolescence, with a maximum interval between seizures of 2 years, aged 15 to 17, with no concurrent change in his antiepileptic drugs (AEDs). Following this, however, his epilepsy remained refractory to medical treatment. Habitual seizures occurred during wake and sleep, and had always been stereotyped. Seizures consisted of an initial indescribable feeling in his head and/or moving up the right arm followed by hypermotor movements of the right arm, sometimes spreading to the right leg and the whole of the right side. Seizure duration was always 10–30 s, and movements were large amplitude, ‘jerky’ and non-purposeful with no posturing. Nocturnal seizures sometimes featured alteration in awareness, but there was always rapid recovery with no postictal confusion. Throughout most of his adult life, he received high doses of phenytoin (PHT 600 mg/day) and carbamazepine (CBZ 1400–1600 mg/day) without seizure control from the sequential addition of valproate, primidone, clonazepam, …

Autoimmune pancreatitis (AIP) is the only pancreatic disorder responsive to steroid treatment. AIP has recently been subclassified into type 1 and type 2 AIP.1 Type 1 AIP is the pancreatic manifestation of immunoglobulin G4 (IgG4)-associated systemic disease (ISD), a fibroinflammatory autoimmune disorder that involves multiple organ systems and is characteristically associated with elevation of serum levels of IgG4.2 Commonly used diagnostic criteria for AIP include the Asian Consensus diagnostic criteria3 and the Mayo Clinic HISORt criteria4 (histology, imaging, serology, other organ involvement and response to corticosteroid treatment). Treatment protocols for AIP are still evolving, but corticosteroids are generally considered to be very effective in the initial inflammatory phase of the disease. Several small case series have reported that corticosteroids are effective in inducing remission in AIP, but larger series and controlled trials are lacking. In this issue of Gut ( see page 1504 ), Kamisawa and colleagues5 report results from a large, multicentre, retrospective survey of 563 patients with AIP treated at 17 referral centres in Japan. Their study highlights the fact that though a substantial proportion of patients with AIP may achieve spontaneous remission (77/104 patients, 74%), corticosteroids are also highly effective in inducing remission (451/459 patients, 98%). This study, despite the limitations of a retrospective and cross-sectional study design, provides the best evidence to date of the efficacy of corticosteroid treatment in the initial presentation of AIP. However, our knowledge of the natural history of AIP, predictors of relapse, need for maintenance treatment and the optimal type of maintenance treatment is still limited. The objective of this commentary is to provide a brief overview of the issues associated with corticosteroid treatment in AIP. The goals of treatment in the initial inflammatory phase of AIP are symptom alleviation (eg, jaundice and abdominal discomfort), …

OBJECTIVE--Investigation of spontaneously resolving lesions associated with epilepsy. DESIGN--Observational study during one year. SETTING--One neurology department. PATIENTS--4 cases in patients (one of Indian parents, one African, one white English, and one Afro-Caribbean) resident in the United Kingdom, who presented with transient epilepsy. MAIN OUTCOME MEASURES--Findings on computed tomography and on screening for infections. RESULTS--In all four cases a small mass lesion in one cerebral hemisphere was observed on computed tomography, which resolved after 9, 4, 3 and 1.5 months respectively without surgery. CONCLUSIONS--The number of cases seen in one year suggests that the lesions may be more common in the United Kingdom than previously recognised and that research into their cause is warranted.

A 63 year old white woman presented with abdominal discomfort, anorexia, and weight loss. Investigations showed hepatocellular carcinoma with pulmonary metastases. The primary and secondary tumours resolved without specific treatment.

Optical coherence tomography (OCT) has indicated that myopic foveoschisis (MF) is not uncommon in highly myopic eyes.1 MF is often accompanied by a macular hole (MH),2,3 while a MH often complicates a retinal detachment (MHRD) in highly myopic eyes. MHRD is believed to result from MF at least in some cases, however, the detail of the process is unknown. We have documented the process of spontaneous resolution of MF and development of RD over a few months. A 65 year old man with high myopia was referred to our clinic with bilateral visual loss and metamorphopsia of 3 months’ duration. OCT revealed MF without MH in his right eye and MF with MH in his left eye (fig 1A and C). His right eye underwent vitrectomy, but the left eye was observed. The initial best corrected visual acuity (BCVA) in his left eye was 20/50 and the axial length was 28.42 mm. …

Survivors of traumatic brain injury (TBI) often suffer from significant adverse physical, neuropsychological, and social sequelae. TBI may pose significant risks to pituitary function;1–5 untreated hypopituitarism may aggravate these adverse consequences. Studies on the natural history of post-TBI hypopituitarism are lacking, and the reversibility of hormone deficits remains uncertain. We describe a case of a man who suffered a transient period of secondary hypoadrenalism after a serious TBI. This is the first reported case of reversible isolated adrenocorticotrophic hormone (ACTH) deficiency following head trauma. An 18 year old man was assaulted on 14 September 2003 and immediately admitted to the local accident and emergency unit with a Glasgow Coma Scale (GCS) score of 3/15 and constricted pupils. Brain computed tomography (CT) revealed multiple small bleeds involving the basal ganglia, left cerebellum, and midbrain, and a left maxilla linear fracture. No other serious injuries were found. He was ventilated on admission, supported in the intensive care unit, and 4 days later transferred to a trauma ward with an unaltered brain CT. Over the next 7 weeks, his GCS remained reduced (6–11/15) with a marked improvement after this time. During his acute recovery phase, no hypotensive insults were recorded, but he had episodes of …

A 64 year old female patient with seropositive rheumatoid arthritis (RA) diagnosed in 1997 was referred to our hospital in March 2002, because of high disease activity despite methotrexate (MTX)-sulfasalazine treatment. After exclusion of contraindications infliximab treatment in combination with MTX was started, with good response. At clinical control before the 16th infliximab infusion the patient reported problems with her sinuses. In a computed tomography (CT) scan of that region reactive lymphatic tissue was suspected. Because of the small size (3.5 to 2.8 cm) of the lesion, lymphoma or hypopharynx carcinoma was ruled out. Despite the benign features of the lesion a biopsy was performed, because of the increased risk of malignancy in RA1–3 during disease modifying antirheumatic drug (DMARD) treatment.4,5 Histopathological evaluation and immunohistochemistry led to the diagnosis of an …

We report the conservative treatment of a spontaneous spinal epidural haematoma attending with acute extensive neurological deficits, which resolved spontaneously. Spontaneous remission of spontaneous spinal epidural haematoma with severe neurological deficit is rare in the literature. An 80 year old man was admitted to our hospital presenting sciatica followed by rapid development of paraparesis and cauda equina syndrome, which represents a neurosurgical emergency. Magnetic resonance imaging revealed a multilevel epidural haematoma from L1 to L5. During the initial diagnostic procedure the symptoms started to decline unexpectedly, so the surgical intervention could be withdrawn. Twenty four hours after admission the patient was almost free of symptoms, mobile, and continent. Awareness and high index of suspicion, and a willingness to seek the prompt help of the imaging department, are crucial to successful management before the opportunity to treat is lost.

Anorexia nervosa is an intense fear of weight gain, inaccurate perception of body size, weight or shape, amenorrhoea, and a body weight

A 45-year-old patient on lifelong warfarin therapy after a metal aortic valve replacement developed a homonymous visual field defect following an occipital lobe haemorrhage. The patient received only conservative management and yet described continued improvement in her visual field defect for up to 20 months following the initial cerebral insult. We present the first conclusive illustrative documentation of visual recovery in a patient with an occipital lobe haemorrhage with sequential automated perimetric assessments over an extended period of time.

In recent years it has been shown that remission may be a realistic goal to aim for when treating rheumatoid arthritis. How to define remission has been a matter of debate, often initiated by the observation that a certain definition allows for the presence of some symptoms or signs that would indicate residual disease activity, or by the expectation that with time, residual disease activity would become apparent. More stringent definitions, with longer follow up requirements, are then proposed. When aiming to be a gold standard of absent disease, to test new methods of measuring disease activity, remission definitions would be have to be so stringent as to denote ‘cure’, if this exists in RA. In daily practice and in most dictionaries remission, coming from Latin remittere , to send back, is called a situation where in a chronic disease (remission does not mean cured), by active intervention (there is no ‘spontaneous remission’, only regression or resolution) there are no longer symptoms. This means that patient and physician need only to agree that the patient is free of clinical manifestations of the disease, and that laboratory signs, lingering evidence of chronicity, persistence of risk factors or abnormal cells or cell activities, need not be absent. Used in daily practice, time efficient methods are needed, that provide sufficient security to allow treatment decisions based on the result. In RA, where previous disease activity may have caused damage, this may result in symptoms which are not clinical manifestations of disease activity. Such symptoms do not preclude that remission may be achieved. Composite scores which include signs of inflammation may help to assess if there is ‘remission with symptoms’. Various composite scores come with their own definition of remission, and these may not all identify the same patients. In research papers on cohorts and observational studies, it is sufficient to use clinical remission criteria. In order to be able to compare outcomes between studies, it would be helpful to report data using the same remission definition in each study. Whether one definition is better than the others and if so, why, will be discussed. Disclosure of Interest None Declared

Background Data of multiple observational cohorts and trials indicate that rheumatoid arthritis patients who were treated in a very early disease phase had a better outcome; these patients developed more often spontaneous remission and less joint damage. Recognizing arthritis in the first 12 weeks after symptom onset is therefore of great importance. In the Leiden area, only 31% of the patients were identified within 12 weeks. General practitioner (GP) delay was the major contributor to the total delay (median 11.8 weeks out of a total delay of 18.4 weeks). 1 It appeared that GPs have difficulties in recognizing arthritis of small joints in an early phase and in case of doubt “wait-and-see99. To diminish this GP delay we initiated an Early Arthritis Recognition Clinic (EA R C) and GPs were encouraged to send any patients to the EARC in whom they doubted about the presence of synovitis. On the EA R C, patients were screened, by experienced rheumatologists, for the presence of synovitis. The EA R C was initiated at two places (Leiden and Groningen University Medical Center). Objectives The present study aimed to evaluate the first year results of the EA R C and to study whether this initiative decreased the delay in recognizing arthritis. Methods 400 Patients visited the Leiden EA R C and 212 patients the Groningen EA R C. At this screening clinic, patients filled in a form with questions about their symptoms and motivations to seek medical attention. Immediately hereafter, they were seen by an experienced rheumatologist for a full joint examination. In case of presence of arthritis patients were seen back within one week for a full work-up. We studied the total delay (period between first symptom and first visit to the EA R C), the GP delay (period between first visit at the GP and first visit at the rheumatologists) and patient delay (period between the first symptom and the first visit to a GP). The effectiveness of the EA R C was evaluated with the GP delay. Results Arthritis was detected in 42.3% of the patients seen in Leiden and in 49.1% of the patients seen in Groningen. In these arthritis patients, the median patient delay was 2.6 (IQR 0.6-8.9) and 2.7 (IQR 0.9-10.3) weeks respectively. The median GP-delay was 2.0 (0.4-7.2) and 2.0 (0.4-10.0) weeks and the median total delay was 8.6 (3.4-22.3) and 10.6 (3.1-30.8) weeks for Leiden and Groningen patients respectively. In addition, 56.8% and 44.2% of the patients with arthritis were seen within 12 weeks after symptom onset. Analyzing only the early arthritis patients that were initially diagnosed with UA or RA revealed that 63.2% and 38.6% respectively were seen Conclusions This established EA R C reduced the GP delay from 8 weeks to 2 weeks and the percentage of patients that were recognized R C importantly increases the early identification of arthritis and RA. References [1]van der Linden MP, le Cessie S, Raza K, et al., Arthritis Rheum 2010;62:3537–46. Disclosure of Interest None Declared

A 76-year-old man presented 5 months following an open cholecystectomy with a complicated retroperitoneal abscess secondary to a retained gallstone, which was misdiagnosed as a tuberculous abscess. Subsequently, the stone was eventually spontaneously discharged with complete resolution of the associated collection.

A term neonate with a transient form of Behçet's disease (BD) is described. The mother had a 3-year history of BD treated with corticosteroids, which remained in remission during pregnancy. On day 1 of life, the neonate was noted to have papulopustular lesions of the labia and perineum. She remained clinically well and bacterial and viral infection screens were negative. The lesions disappeared within 3 weeks without scarring. No recurrence has been reported.

A healthy 78-year-old man was admitted with a 3-day history of epigastric pain and bilious vomiting. Ultrasound revealed cholelithiasis with a normal calibre common bile duct. The patient subsequently underwent an upper gastrointestinal endoscopy which demonstrated a large …

Spontaneous mesenteric haematomas are rare. They have been reported to be associated with coagulopathies, connective tissue disorders, past trauma, arteriopathy and pancreatitis. However, some cases have been reported in which there is no apparent underlying aetiology. Here we report such a case and we review the literature that discusses optimal diagnosis and management. In this case, spontaneous haemostasis occurred by intra-abdominal tamponade and the regression of the haematoma was monitored with regular imaging.

Immune Thrombocytopenia Purpura (ITP) is a relatively common paediatric presentation (3-8 cases per 100,000). It is usually a benign condition with spontaneous resolution occurring in 80% of cases within 6 months. Chronic ITP is only rarely associated with severe symptoms and the mainstay of treatment remains supportive care. We describe an unusual case of chronic relapsing symptomatic ITP whose refractory nature challenged conventional treatment options and triggered reflection on ITP management. 3 year old AS presented acutely with fever and extensive petechiae, following a 6 month history of easy bruising. She was initially treated for meningococcaemia but a diagnosis of ITP was subsequently made based on the findings of an isolated thrombocytopenia (with an otherwise normal blood film) in the absence of hepatospenomegaly or lymphadenopathy. Initial management was conservative. However, symptomatic cutaneous and mucosal bleeding continued associated with thrombocytopenia ( Lymphoproliferative, autoimmune and post-viral causes were excluded and empirical treatments were given for symptom relief. Prednisolone was ineffective and intravenous immunoglobulin provided only short-lived improvement. As symptoms persisted, a second line agent rituximab was given, achieving 10 months of remission. Following further relapse, a second course of rituximab achieved remission prior to performing a laparoscopic splenectomy. Despite this she relapsed again 6 months later. Treatment options were again reviewed and oral dapsone was started. This was ineffective and stopped due to symptomatic methaemoglobinaemia (22.6%). It was subsequently restarted at a lower dose but she again developed methaemoglobinaemia and therefore dapsone was discontinued and a yellow card was completed to highlight this dramatic reaction. Following national discussions, she was enrolled for a trial of a TPO-receptor agonist. However, whilst awaiting entry into this trial, she developed spontaneous remission – 2.5 years following initial diagnosis. Chronic ITP is rarely associated with significant thrombocytopenia and symptomatology. Medical and surgical treatments can effect remission but therapeutic cure is unusual. It is therefore essential to weigh up the risk balance when considering treatment. This case clearly highlights this point and prompts consideration of the indications for medical treatment in chronic ITP and of where the risk-benefit balance lies in complex cases such as this.

Aims To highlight a rare respiratory condition, its investigation and management. Methods A 12 year old girl referred by GP to her local DGH with a history of worsening exertional and nocturnal dyspnoea, and weight loss subsequent to a flu like illness one year previously. Past medical history was unremarkable. Her exercise tolerance was severely restricted due to cough and shortness of breath. She had shown no response to either bronchodilators or inhaled steroids. She had been treated with 3 courses of oral antibiotics for presumed chest infections without improvement. Results She was dyspnoeic at rest, hypoxic in room air (85%), which improved to 93% in 1 litre of oxygen. She was thin but not clubbed. She had marked pectus excavatum. She had markedly reduced air entry and coarse crackles bilaterally. Her chest X-ray showed widespread interstitial shadowing. She had normal routine bloods, blood gas, and ECG. Her FEV1 was 30% predicted with a restrictive flow-volume loop. Her differential diagnoses included pneumocystis pneumonia, drug reaction, interstitial lung disease, and alveolar proteinosis. She was referred to her regional respiratory centre. Further investigations of note were: ▶Pneumocyctis PCR: Negative ▶Bronchoscopy: Normal airway anatomy. Creamy BAL fluid. ▶Immune function: Normal ▶CT Chest: widespread alveolar and interstitial change, with ‘crazy paving’ ▶Echo: Normal ▶Quantiferon & AFB staining: Negative ▶BAL showed abnormal cytology, with amorphous proteinaceous debris. Strongly PAS stain positive, diagnostic for Pulmonary Alveolar Proteinosis (PAP). She also grew haemophilus resistant to amoxicillin, commenced on co-amoxiclav. Conclusion PAP can present in the neonatal period, due to surfactant protein B deficiency, and is usually fatal. Later onset disease can be related to disturbance of granulocyte-macrophage colony stimulating factor (GM-CSF), and is diagnosed on BAL without the need for lung biopsy. CT appearances are suggestive. She was referred to the Royal Brompton for bilateral whole lung lavage. Ongoing care issues include correction of hypoxaemia, improving nutritional status, repeat lavage treatment and consideration of inhaled GMCSF. This condition has a variable course. Some patients will have spontaneous remission, some will have their disease controlled with multiple lavage treatments and some have disease with progression to respiratory failure.