Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment. CONCLUSION: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

A Historic Cohort Analysis of Radiographic and Serologic Findings in Patients With Scleroderma and Interstitial Lung Disease.

BACKGROUND/OBJECTIVE: Few studies have investigated associations between rheumatologic serology patterns and different interstitial lung disease (ILD) patterns. METHODS: We present novel findings of a historic cohort study (n = 454) with data collected from 2011 to 2021 within our hospital system. In this institutional review board-approved study, data regarding rheumatologic serologies and ILD patterns were noted based on chart review in patients with scleroderma. The Kruskal-Wallis rank sum and χ2 tests were used for statistical analysis. RESULTS: Results showed a statistically significant association between anti-U1 snRNP with lymphoid interstitial pneumonia, which has not been previously described. CONCLUSIONS: We demonstrated novel serologic associations with ILD patterns, which have important clinical implications. More robust and high-powered studies are needed to elucidate the role of serologic testing and their association with ILD phenotypes.

Skin disorders and interstitial lung disease: Part I-Screening, diagnosis, and therapeutic principles.

Numerous inflammatory, neoplastic, and genetic skin disorders are associated with interstitial lung disease (ILD), the fibrosing inflammation of lung parenchyma that has significant morbidity and mortality. Therefore, the dermatologist plays a major role in the early detection and appropriate referral of patients at risk for ILD. Part 1 of this 2-part CME outlines the pathophysiology of ILD and focuses on clinical screening and therapeutic principles applicable to dermatological patients who are at risk for ILD. Patients with clinical symptoms of ILD should be screened with pulmonary function tests and high-resolution chest computed tomography. Screening for pulmonary hypertension should be considered in high-risk patients. Early identification and elimination of pulmonary risk factors, including smoking and gastroesophageal reflux disease, are essential in improving respiratory outcomes. First-line treatment interventions for ILD in a dermatological setting include mycophenolate mofetil, but the choice of therapeutic agents depends on the nature of the primary disease, the severity of ILD, and comorbidities and should be the result of a multidisciplinary assessment. Better awareness of ILD among medical dermatologists and close interdisciplinary collaborations are likely to prevent treatment delays improving long-term outcomes.

Skin disorders and interstitial lung disease: Part II-The spectrum of cutaneous diseases with lung disease association.

Part 2 of this 2-part CME introduces dermatologists to noninfectious inflammatory skin diseases associated with pulmonary involvement. In many cases, dermatologists may be the first physicians recognizing respiratory complications associated with these diagnoses. Because pulmonary involvement is often the leading cause of morbidity and mortality, dermatologists should be comfortable screening and monitoring for lung disease in high-risk patients, recognizing cutaneous stigmata of lung disease in these patients and referring to pulmonary specialists, when appropriate, for prompt treatment initiation. Some treatments used for skin disease may not be appropriate in the context of lung disease and hence, choosing a holistic approach is important. Interstitial lung disease and pulmonary hypertension are the most common pulmonary complications and a significant cause of mortality in autoimmune connective tissue diseases, especially systemic sclerosis, dermatomyositis, and mixed connective tissue disease. Pulmonary complications, notably interstitial lung disease, are also common and life-threatening in sarcoidosis and vasculitis, while they are variable in neutrophilic and autoimmune blistering diseases.

Interstitial Lung Disease in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Patients: Comparison With Idiopathic Pulmonary Fibrosis.

BACKGROUND/OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may involve the kidney, respiratory tract, skin, or central and peripheral nervous system. Reports of interstitial lung disease (ILD) in AAV (AAV-ILD) have been increasing. METHODS: We reviewed the medical records of all patients with AAV-ILD between January 1, 2007, and December 31, 2017, and compared their pulmonary involvement to patients with idiopathic pulmonary fibrosis (IPF). RESULTS: We identified 24 patients with AAV-ILD: 14 with microscopic polyangiitis, 8 with granulomatosis with polyangiitis, and 2 with eosinophilic granulomatosis with polyangiitis. Perinuclear or myeloperoxidase ANCA was present in 16 cases (66.7%), whereas cytoplasmic or proteinase 3 ANCA was positive in 8 (33.3%). Usual interstitial pneumonia (UIP) was seen in 11 (45.8%), probable UIP in 1 (4.2%), indeterminate UIP in 2 (8.3%), and an alternate diagnosis in 10 (41.7%), and was further characterized as chronic hypersensitivity pneumonitis-like pattern seen in 6 (25%), nonspecific interstitial pneumonia-like pattern in 3 (12.5%), and cryptogenic organizing pneumonia-like pattern in 1 (4.2%). Forced vital capacity and diffusing capacity declined over time in patients with AAV-ILD. When compared with the IPF cohort, patients with AAV-ILD had intermediate survival and speed of lung function decline (3-year survival in AAV-ILD group was 94% vs 69% in IPF). CONCLUSIONS: Antineutrophil cytoplasmic antibody-associated vasculitis ILD is a progressive and potentially fatal condition. Although most cases in the literature are associated with p-ANCA and positive myeloperoxidase, we found that a third of patients had c-ANCA or granulomatosis with polyangiitis. Our cohort adds experience in this rare manifestation of AAV.

Opioid Use in Fibromyalgia Continues Despite Guidelines That Do Not Support Its Efficacy or Risk.

BACKGROUND/OBJECTIVE: The aim of this cross-sectional study is to determine the prevalence of opioid use in a large sample of fibromyalgia (FM) patients and examine the factors associated with opioid prescription/use despite multiple clinical guidelines that do not recommend opioid use in this population. METHODS: Data were collected from a convenience sample of 698 patients admitted from August 2017 to May 2019 into an intensive 2-day Fibromyalgia Treatment Program at a tertiary medical center in the United States after FM diagnosis. Patients were administered the Fibromyalgia Impact Questionnaire-Revised, the Center for Epidemiologic Study of Depression Scale, and the Pain Catastrophizing Scale upon admission to the program. Demographic information and opioid use were self-reported. Logistic regression analysis was utilized to determine associations between patient-related variables and opioid use in this prospective study. RESULTS: Of 698 patients, 27.1% (n = 189) were taking opioids at intake. Extended duration of symptoms (>3 years), increased age, higher degree of functional impairment, and increased pain catastrophizing were significantly associated with opioid use. CONCLUSIONS: Opioids are not recommended for the treatment of FM under current guidelines. Greater burden of illness appeared to be associated with the prescription and use of opioids in this population. These findings suggest that some providers may not be aware of current recommendations that have been found to be effective in the management of FM that are contained in guidelines. Alternative approaches to the management of FM that do not involve opioids are reviewed in an effort to improve care.

Intensive Multicomponent Fibromyalgia Treatment: A Translational Study to Evaluate Effectiveness in Routine Care Delivery.

OBJECTIVE: The current study was designed to evaluate the translation of clinical trial outcomes and clinical guidelines for the treatment of fibromyalgia (FM) into an intensive multicomponent clinical program embedded in routine care delivery. The study aimed to assess the adaptation of these recommended strategies into routine clinical care while evaluating their effectiveness and durability in improving functional status and level of distress in a large clinical sample of FM patients. METHODS: Four hundred eighty-nine patients with FM completed a 2-day program that incorporated best practice recommendations for the treatment of FM. Patients completed the Fibromyalgia Impact Questionnaire-Revised, the Center for Epidemiologic Studies Depression Scale, and the Pain Catastrophizing Scale at admission to the program and at follow-up on average 5 months posttreatment. RESULTS: Significant improvements were seen in functional status (p < 0.0001), depressive symptoms (p < 0.0001), and pain catastrophizing (p < 0.0001) after participation in the intensive multicomponent treatment program. CONCLUSIONS: The present study shows that an intensive multicomponent treatment program embedded in routine care delivery is effective in significantly improving functional status and psychological distress in a large sample of FM patients. The significant improvements were durable and maintained at follow-up.

Lupus Vasculitis.

PURPOSE OF REVIEW: The purpose of this manuscript is to review the most recent literature pertinent to the presence of vasculitis in patients with systemic lupus erythematosus (SLE), including previously published landmark articles and studies and to update the different clinical and diagnostic aspects of vasculitic manifestations in patients with this important autoimmune disorder. As a multisystem autoimmune disease, systemic lupus may attack practically any organ system in the human body. Even though vasculitis is not the most common presentation or pathogenic mechanism of disease, it frequently causes significant morbidity and mortality in patients with SLE. The most common manifestation of lupus vasculitis is cutaneous involvement; visceral involvement is less common but causes severe disease; it may occur in different areas including central nervous system, peripheral nervous system, gastrointestinal system, kidneys, lungs and even retina. RECENT FINDINGS: Recent findings regarding the pathogenesis of lupus CNS and peripheral nerve disease, and vascular injury in lupus nephritis are reviewed as well. Vasculitis is an uncommon but serious manifestation of SLE; it may involve different organ systems and present in a wide variety of clinical syndromes, and thus the importance of its recognition and early diagnosis by physicians who deal with this disease, in order to start prompt and aggressive therapy when indicated.

Gastrointestinal Manifestations of Rheumatological Diseases.

Rheumatological diseases (RDs) represent a diverse group of diseases that are inherited or related to environmental factors. RDs frequently affect the gastrointestinal (GI) tract, and gastroenterologists are often asked to evaluate patients with symptoms thought to represent an underlying or coexisting RD. GI manifestations of RDs vary based on the organ involved as well as the extent and duration of involvement. Although most manifestations of RD are nonspecific and not life-threatening, the chronicity and severity of symptoms can be debilitating and may lead to serious injury. This narrative review discusses the most common RD encountered by gastroenterologists: systemic lupus erythematosus, systemic sclerosis (scleroderma), dermatomyositis/polymyositis, rheumatoid arthritis, Sjögren syndrome, overlap syndromes, mixed connective tissue disease, Ehlers-Danlos syndromes, and other vasculitides. Each section begins with a brief overview of the condition, followed by a discussion of the etiopathophysiology, physical examination findings, GI manifestations, diagnostic tools (i.e., serologic, imaging, endoscopic, and functional), and treatment options.

Association of antinuclear antibody status with clinical features and malignancy risk in adult-onset dermatomyositis.

BACKGROUND: The clinical significance of antinuclear antibody (ANA) status in adults with dermatomyositis (DM) has yet to be fully defined. OBJECTIVE: We compared the incidence of amyopathic disease, risk of malignancy, and clinical findings in ANA+ and ANA- patients with adult-onset DM. METHODS: This was a retrospective cohort study of patients with ANA+ or ANA- adult-onset DM determined by enzyme-linked immunosorbent assay. RESULTS: Of 231 patients, 140 (61%) were ANA+ and 91 (39%) were ANA-. Compared with the ANA- patients, the ANA+ patients had a lower frequency of dysphagia (15% vs 26% [P = .033]) and heliotrope rash (38% vs 53% [P = .026]). In all, 54 patients (23%) developed malignancy within 3 years of diagnosis of their DM; 11% of the ANA+ patients developed malignancy versus 43% of the ANA- patients (P < .001). There was a strong association between ANA positivity and lower likelihood of malignancy in multivariable analysis (odds ratio, 0.16; P < .001). Conversely, ANA positivity was not associated with amyopathic disease (odds ratio, 0.94; P = .87). LIMITATIONS: The retrospective nature of the study was a limitation. CONCLUSION: In patients with adult-onset DM, ANA negativity is associated with increased likelihood of development of malignancy within 3 years of diagnosis of their DM. Particularly close follow-up and frequent malignancy screening may be warranted in ANA- individuals with DM.

Reliability of OMERACT ultrasound elementary lesions in gout: results from a multicenter exercise.

The aim of this study was to evaluate the reliability of the outcome measures in rheumatology (OMERACT) definitions for ultrasound (US) elementary lesions in gout through an image reading exercise. Images from patients with gout (static images and videos) were collected. As an initial step, we carried out a image reading exercise within the experts of the Pan-American League of Associations for Rheumatology (PANLAR) US Study Group (n = 16). The following step consisted in a web-based exercise with the participation of larger number of sonographers (n = 63) from different centers. Images were rated evaluating the presence/absence of any US elementary lesion. Inter- and intra-reader reliabilities were analyzed using kappa coefficients. Participants were stratified according to their level of experience. In the first exercise, inter-reader kappa values were 0.45 for aggregates, 0.57 for tophus, 0.69 for erosions, and 0.90 for double contour (DC). Intra-reader kappa values were 0.86, 0.76, 0.80, and 0.90, respectively. The web-based exercise showed inter-reader kappa values for aggregates, tophus, erosions, and DC of 0.42, 0.49, 0.69, and 0.79, respectively. The intra-reader kappa values were 0.62, 0.69, 0.77, and 0.85, respectively. Reliability was not influenced by the sonographer's level of experience. The reliability of the new OMERACT US definitions for elementary lesions in gout ranged from moderate to excellent, depending on the type of lesion.

Interstitial lung disease in patients with mixed connective tissue disease: pilot study on predictors of lung involvement.

OBJECTIVES: Mixed connective tissue disease (MCTD) is an immune-mediated systemic disorder characterised by serum autoantibodies against U1-ribonucleoprotein and diverse multisystemic clinical manifestations. Approximately 50% of patients with MCTD develop a radiologic pattern of interstitial lung disease (ILD). Our single centre, cross-sectional study sought to identify clinical and serologic associations of ILD in patients with MCTD which may serve as predictors of lung disease and prognosis. METHODS: Patients who met validated criteria for diagnosis of MCTD were included in the study, and were further differentiated into study and control groups based on presence or absence of ILD. RESULTS: Multivariate logistic regression showed an association of two clinical variables: dysphagia with an R2 value of 0.33 (p-value <0.001) and Raynaud's phenomenon with R2 value of 0.28 (p-value <0.001). CONCLUSIONS: An association of dysphagia with the development of ILD in our study is in harmony with the existing literature. There are primarily case reports, suggesting an association of Raynaud's phenomenon with development of ILD in patients with undifferentiated CTD. To our knowledge, this is the first study highlighting the association of Raynaud's phenomenon with development of ILD in patients with MCTD. The mechanistic aspects of the association between Raynaud's phenomenon and ILD remain unexplored. The association of easily elicited historical and clinical features of MCTD with subtle, but worrisome, pulmonary pathology carries the promise of sensitising the unsuspecting clinician about the entity of ILD in MCTD.

2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.

Tocilizumab, an effective treatment for relapsing giant cell arteritis.

OBJECTIVES: Patients with giant cell arteritis (GCA) often respond to corticosteroid (CS) therapy; however, the majority of patients relapse when CS therapy is tapered or withdrawn. The purpose of this study was to assess the efficacy of tocilizumab (TCZ) in patients with relapsing GCA. METHODS: Four patients with relapsing GCA received TCZ monthly (4mg/kg or 8mg/kg). Disease activity and drug tolerability were evaluated clinically and via laboratory test results at the beginning of the study and every 3 months until the publication of this study. All four patients were still receiving TCZ monthly at the time of manuscript submission. RESULTS: All four patients treated with TCZ achieved clinical and laboratory response. No adverse events were detected. CONCLUSIONS: In our small case series, TCZ was efficacious and well tolerated in patients with relapsing GCA. Proper randomised controlled trials are required to achieve confident conclusions regarding the safety and efficacy of TCZ in GCA.

Investigating the concomitance of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides and inflammatory bowel disease (IBD).

OBJECTIVE: To assess relationship between Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and inflammatory bowel disease (IBD). METHODS: This is a retrospective study design. The patients were identified using a preset criteria of patients who have the diagnosis of ANCA associated vasculitis including a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) with overlapping inflammatory bowel disease (Crohn's disease or ulcerative colitis) in the time period from 01/01/2020 to 08/03/2023. Subsequently data from each patient was collected that will include baseline demographics, disease characteristics, disease activity, treatment information, multiorgan involvement, and pathology findings which were then analyzed. RESULTS: 39 patients were identified that met criteria. 20 patients carried a diagnosis of GPA, 6 had MPA and 4 patients had EGPA. 20 patients with GPA had inflammatory bowel disease, 13 with ulcerative colitis and 6 with Crohn's disease while 1 GPA patient had unspecified inflammatory bowel disease. 4 patients with EGPA had inflammatory bowel disease, 2 with ulcerative colitis and 2 with Crohn's disease. 6 patients with MPA had inflammatory bowel disease, 4 with ulcerative colitis and 2 with Crohn's disease. IBD diagnosis preceded the diagnosis of ANCA vasculitis in 77.8 % of the cases. CONCLUSION: Objective observation and deductions from this study raise the concern for a possible pathogenic association of ANCA associated vasculitis and inflammatory bowel disease and more research is needed to identify any causal association or influence of the two systemic disease on each other.

Nailfold videocapillaroscopy in antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of illnesses that cause inflammation and alterations to small vessels in the body. Some of the most common and detrimental manifestations, including alveolar hemorrhage and glomerulonephritis, are caused by this capillary inflammation. We sought to clarify whether patients with AAV would have abnormal nailfold capillaries when evaluated with nailfold videocapillaroscopy. METHODS: Patients with a current diagnosis of AAV and a control group were identified for enrollment. Nailfold videocapillaroscopy images were used for a semiquantitative analysis on capillary density, morphology, dilation, and microhemorrhage after review by 2 rheumatologists. Disease characteristics, occurrence of recent disease flare, and presence of ANCA were recorded. RESULTS: Thirty-three patients with a diagnosis of AAV and 21 controls were recruited. The AAV group had a median age of 59 and 17 (52%) were women. Granulomatosis with polyangiitis was the most common diagnosis (19 [58%]), followed by eosinophilic granulomatosis with polyangiitis (7 [21%]) and microscopic polyangiitis (7 [21%]). Twenty-seven patients (82%) had positive ANCA tests. After assessment of capillary density, dilation, morphology, microhemorrhages, and disorganization, there were no statistically significant differences between the 2 groups. CONCLUSION: There was no evidence of differences in nailfold capillaroscopy abnormalities between those diagnosed with AAV and the control group. While this cohort was relatively small, we did not find a high enough prevalence or specific phenotype of capillary abnormalities that could aid in diagnosis or prognostication of these diseases in the clinical setting.

Dermatomyositis in Association With SARS-CoV-2 Infection or COVID-19 Vaccine.

OBJECTIVE: New-onset and relapsed dermatomyositis (DM) has been reported following SARS-CoV-2 infection or COVID-19 vaccination. This study aims to show the characteristics of a DM cohort after COVID-19 infection and vaccination. METHODS: A retrospective review was performed on patients treated for DM between March 1, 2020, and October 31, 2022. Charts were evaluated for the presence of new-onset DM or relapse of preexisting DM following either SARS-CoV-2 infection or COVID-19 vaccination. Data on symptom onset, timing of vaccination, type of vaccination, and disease characteristics were collected. RESULTS: Ninety-eight patients treated for DM at our institution in the Division of Rheumatology were included. In total, 12 of 98 patients (12.2%) experienced DM symptoms (either incident or relapse) following either infection or vaccination. Of the 12 patients who developed incident disease or relapse, 7 (58.3%) developed postinfection symptoms, and 8 (66.7%) developed symptoms after vaccination (3 patients had symptoms following both infection and vaccination). The mean onset of symptoms following COVID-19 infection was 3.2 days (median 0.5 days), and mean onset following COVID-19 vaccination was 5.75 days (median 3.5 days). Nine of 12 patients (75%) had a positive myositis-specific antibody, and the remaining 3 (25%) had myositis-associated antibodies. There was no predominant vaccine associated with the development of postvaccination DM symptoms. CONCLUSION: This retrospective review revealed a strong temporal relationship between DM symptoms and COVID-19 infection or vaccination in 12.2% of all patients with DM evaluated in our clinic during the pandemic. Additional studies are required to understand the possible pathophysiology behind this association.

Bilateral Lumbosacral Plexopathy As the Initial Manifestation of Systemic Sarcoidosis: A Case Report.

Neurosarcoidosis is one of the most relevant involvements in systemic sarcoidosis and can be the initial presentation. Its diagnosis is often considered difficult because of unusual clinical manifestations or diagnostic mimics. The peripheral nervous system is less frequently involved than the central nervous system, although it may also lead to irreversible neurologic impairment. Lumbosacral plexopathy in sarcoidosis is a rare presentation and has been scarcely described in anecdotal case reports and small case series. We describe the case of a 61-year-old female who presented with right inguinal pain, right thigh weakness, and gait limitation, with imaging evidence of bilateral lumbosacral plexopathy as the initial manifestation of systemic sarcoidosis and subsequently developed joint and pulmonary involvement. This case report aims to bring awareness of this involvement as a possible initial manifestation of systemic sarcoidosis and mention key features of the differential diagnosis. Prompt recognition and treatment may prevent neurologic impairment.

2012 Provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain. These criteria are not meant for diagnostic purposes.