Periprocedural Edoxaban Management and Clinical Outcomes in Patients Undergoing Transcatheter Cardiovascular Procedures in the EMIT-AF/VTE Program.

Clinical trial registration number: NCT02950168, NCT02951039.

Management of edoxaban therapy and clinical outcomes in patients undergoing major or nonmajor surgery: a subanalysis of the EMIT-AF/VTE study.

BACKGROUND: Optimising periprocedural management of direct oral anticoagulation in patients with atrial fibrillation on chronic treatment undergoing major surgeries is an important aspect of balancing the risk of surgery-related bleeding with the risk of thromboembolic events, which may vary by surgery type. METHODS: This subanalysis of the prospective EMIT-AF/VTE programme assessed periprocedural-edoxaban management, according to physicians' decisions, and bleeding and thromboembolic event rates in patients who underwent major vs. nonmajor surgeries. Edoxaban interruption and clinical outcomes were compared between major vs. nonmajor surgeries and between renal function subgroups (creatinine clearance [CrCL] ≤ 50 mL/min vs. > 50 mL/min). RESULTS: We included 276 major and 512 nonmajor surgeries. The median pre- and postprocedural duration of edoxaban interruption in major vs. nonmajor surgeries was 4 vs. 1 days, whereas median duration of interruption for those with preprocedural-only and postprocedural-only interruption was 2 vs. 1 days and 2 vs. 0 days, respectively (P < 0.0001). Rates of all bleeding and clinically relevant nonmajor bleeding were numerically higher in major vs. nonmajor surgeries. Event rates (number of events per 100 surgeries) were low overall (< 6 events per 100 surgeries), independent of renal function subgroups. CONCLUSION: In this subanalysis of the EMIT-AF/VTE programme, periprocedural-edoxaban interruption was significantly longer in patients undergoing major vs. nonmajor surgery. This clinician-driven approach was associated with low rates of bleeding and thromboembolic events following both major and nonmajor surgeries. TRIAL REGISTRATION: NCT02950168, registered October 31, 2016; NCT02951039, registered November 1, 2016.

Edoxaban use in the context of dental procedures: analysis from the EMIT-AF/VTE database.

INTRODUCTION: Literature reviews support continuing anticoagulation during dental procedures. However, studies often present grouped anticoagulation data, and information on individual anticoagulant management would be helpful to dentists. The Edoxaban Management in Diagnostic and Therapeutic Procedures (EMIT-AF/VTE) programme (NCT02950168; NCT02951039) demonstrated low periprocedural bleeding and thrombotic event rates in patients with atrial fibrillation receiving edoxaban. AIMS: To report periprocedural edoxaban interruption and clinical events in patients from EMIT-AF/VTE who underwent dental procedures. METHODS: Dental procedures were categorised by type (cleaning/noncleaning). Edoxaban interruption, bleeding events, and thrombotic events were observed 5 days preprocedure through 29 days postprocedure. RESULTS: Overall, 196 patients underwent 350 cleaning and/or noncleaning procedures; most patients (171/196 [87.2%]) underwent noncleaning procedures (282/350 [80.6%]), whereas 48/196 (24.5%) underwent 68/350 (19.4%) cleaning procedures. Edoxaban was uninterrupted for most cleanings (53/68 [77.9%]). Preprocedural interruption was common for single and multiple tooth extractions (single, 67/100 [67.0%]; multiple, 16/30 [53.3%]). The only major bleeding occurred after an unrelated cleaning. Minor bleeding occurred in 1/68 (1.5%) cleaning and 4/282 (1.4%) noncleaning procedures. There were no thrombotic events. CONCLUSIONS: For most cleanings, edoxaban was not interrupted, whereas preprocedural interruption was more common for tooth extractions. Overall, bleeding rates were low, and no thrombotic events occurred.

[COVID-19 vaccination for people with severe mental diseases : Results of the COVID Ψ outpatient survey and recommendations for psychiatry]. / COVID-19-Impfung für Menschen mit schweren psychischen Erkrankungen : Ergebnisse des COVID-Ψ-Ambulant-Surveys und Empfehlungen für die Psychiatrie.

BACKGROUND: Severe mental illnesses are risk factors for SARS-CoV-2-related morbidity and mortality. Vaccination is an effective protection; therefore, high vaccination rates should be a major priority for people with mental illnesses. OBJECTIVES: (1) Identification of at-risk groups for non-vaccination and structures and interventions needed for widespread vaccination among people with mental illnesses from the perspective of outpatient psychiatrists and neurologists, (2) discussion of the results in the context of the international literature and (3) recommendations derived from them. MATERIAL AND METHODS: Qualitative content analysis of COVID-19 vaccination-related questions from the COVID Ψ online survey of n = 85 psychiatrists and neurologists in Germany. RESULTS: In the survey, people with schizophrenia, severe lack of drive, low socioeconomic status and homelessness were seen as risk groups for non-vaccination. Increased and targeted information, education, addressing and motivation and easily accessible vaccination offers by general practitioners, psychiatrists, and neurologists as well as complementary institutions were considered as important interventions. DISCUSSION: COVID-19 vaccinations as well as information, motivation and access support should be systematically offered by as many institutions of the psychiatric, psychotherapeutic and complementary care systems in Germany as possible.

Mental, Neurological, and Somatic Comorbidities and Their Treatment in Persons With Intellectual Disability.

BACKGROUND: Persons with intellectual disability (ID) often suffer from significant comorbidities. As data have been lacking until now, the present report is the first one containing outpatient data on the prevalence of ID in Germany, its comorbidities, and outpatient (drug) treatment. METHODS: This study is based on the nationwide outpatient billing data and drug prescription data of all SHI-insured adults (SHI, statutory health insurance) (age 18-109) who were seen at least once in an outpatient medical practice in 2018. Patients with at least two F70-F79 diagnoses in two quarters were included in the study group (SG) (n = 324 428). A random sample of patients without ID served as the control/comparison group (CG) (n = 648 856). The odds ratios (SG vs. CG) for comorbidities, prescriptions of selected classes of drugs, and involvement of medical specialties were each analyzed by multivariate logistic regression. RESULTS: The prevalence of ID was 0.55%. ID was found to be associated with a variety of comorbidities. The highest odds ratios [OR] were for infantile cerebral palsy (OR: 121.71; 95% confidence interval: [111.67; 132.67]), autism spectrum disorders (OR: 83.85 [75.54; 93.08]), and developmental disabilities (OR: 61.34 [58.86; 63.94]). The most frequently prescribed drug categories (as classified by the anatomic-therapeutic-chemical (ATC) convention) were psychoactive drugs (antipsychotic, anxiolytic, and hypnotic drugs and sedatives) and antiepileptic drugs (OR: 10.40 [10.27; 10.53] and 9.90 [9.75; 10.05], respectively). Both general practitioners (OR: 2.64 [2.59; 2.69]) and medical specialists were consulted by the SG more frequently than by the CG; the type of specialist most commonly consulted was in the neuropsychiatric field, i.e., a neurologist or psychiatrist (OR: 6.85 [6.77; 6.92]). CONCLUSION: A diagnosis of ID frequently appears in outpatient billing data. Future analyses should be devoted to the specific care of people with intellectual disability, who constitute an especially multimorbid and vulnerable patient group.

A clinically applicable gene expression-based score predicts resistance to induction treatment in acute myeloid leukemia.

Prediction of resistant disease at initial diagnosis of acute myeloid leukemia (AML) can be achieved with high accuracy using cytogenetic data and 29 gene expression markers (Predictive Score 29 Medical Research Council; PS29MRC). Our aim was to establish PS29MRC as a clinically usable assay by using the widely implemented NanoString platform and further validate the classifier in a more recently treated patient cohort. Analyses were performed on 351 patients with newly diagnosed AML intensively treated within the German AML Cooperative Group registry. As a continuous variable, PS29MRC performed best in predicting induction failure in comparison with previously published risk models. The classifier was strongly associated with overall survival. We were able to establish a previously defined cutoff that allows classifier dichotomization (PS29MRCdic). PS29MRCdic significantly identified induction failure with 59% sensitivity, 77% specificity, and 72% overall accuracy (odds ratio, 4.81; P = 4.15 × 10-10). PS29MRCdic was able to improve the European Leukemia Network 2017 (ELN-2017) risk classification within every category. The median overall survival with high PS29MRCdic was 1.8 years compared with 4.3 years for low-risk patients. In multivariate analysis including ELN-2017 and clinical and genetic markers, only age and PS29MRCdic were independent predictors of refractory disease. In patients aged ≥60 years, only PS29MRCdic remained as a significant variable. In summary, we confirmed PS29MRC as a valuable classifier to identify high-risk patients with AML. Risk classification can still be refined beyond ELN-2017, and predictive classifiers might facilitate clinical trials focusing on these high-risk patients with AML.

[Experience of Practice-Based Psychiatrists and Neurologists During the COVID-19 Pandemic]. / Erfahrungen und Belastungserleben niedergelassener Neurologen und Psychiater während der COVID-19-Pandemie.

AIM: To date, to our knowledge there are no studies regarding attitudes and experiences of outpatient medical personnel during a pandemic. This study's aim was to evaluate the impact of the COVID-19 pandemic in March 2020 on German psychiatrists and neurologists. METHODS: An e-mail and fax-based short survey of 2,072 practice-based psychiatrists and neurologists was performed including Likert-type questions on personal burden and concerns, anticipated risk of infection, practice management as well as anxiety and sleep problems. RESULTS: 396 physicians returned the questionnaire (19 %). More than 60 % of the participants felt restricted strongly or very strongly, more than 30 % were strongly and very strongly concerned. They anticipated a high own risk of infection. However, 91 % did not report any contact with patients positively screened for COVID-19, which they were aware of. One third felt financially threatened and loss of business volume was anticipated. 18 % reported, that the pandemic triggers substantial anxiety. Sleep problems, which occur at least almost every night, were rarely reported (9 %). CONCLUSION: Practice-based psychiatrists and neurologists are negatively affected by the COVID-19 pandemic.

Innovations and changes in the ICD-11 classification of mental, behavioural and neurodevelopmental disorders.

Following approval of the ICD-11 by the World Health Assembly in May 2019, World Health Organization (WHO) member states will transition from the ICD-10 to the ICD-11, with reporting of health statistics based on the new system to begin on January 1, 2022. The WHO Department of Mental Health and Substance Abuse will publish Clinical Descriptions and Diagnostic Guidelines (CDDG) for ICD-11 Mental, Behavioural and Neurodevelopmental Disorders following ICD-11's approval. The development of the ICD-11 CDDG over the past decade, based on the principles of clinical utility and global applicability, has been the most broadly international, multilingual, multidisciplinary and participative revision process ever implemented for a classification of mental disorders. Innovations in the ICD-11 include the provision of consistent and systematically characterized information, the adoption of a lifespan approach, and culture-related guidance for each disorder. Dimensional approaches have been incorporated into the classification, particularly for personality disorders and primary psychotic disorders, in ways that are consistent with current evidence, are more compatible with recovery-based approaches, eliminate artificial comorbidity, and more effectively capture changes over time. Here we describe major changes to the structure of the ICD-11 classification of mental disorders as compared to the ICD-10, and the development of two new ICD-11 chapters relevant to mental health practice. We illustrate a set of new categories that have been added to the ICD-11 and present the rationale for their inclusion. Finally, we provide a description of the important changes that have been made in each ICD-11 disorder grouping. This information is intended to be useful for both clinicians and researchers in orienting themselves to the ICD-11 and in preparing for implementation in their own professional contexts.

Quality of life and patient satisfaction in patients with atrial fibrillation on stable vitamin K antagonist treatment or switched to a non-vitamin K antagonist oral anticoagulant during a 1-year follow-up: A PREFER in AF Registry substudy.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are being introduced for stroke prevention in non-valvular Atrial Fibrillation (AF), and promise to be accepted better than Vitamin K Antagonists (VKAs) by patients, improving their Quality of Life (QoL). AIM: To assess to what extent patient-related factors influence decisions to switch from a VKA to a NOAC. METHODS: The PREFER in AF Registry collected data at baseline in 2012 - at the beginning of NOAC prescriptions - and at 1-year follow-up, in 6412 patients in seven Western European countries. QoL and patient satisfaction questionnaires (EQ-5D-5L and/or PACT-Q2) were completed in 3777 patients at both visits. Data were compared across categories of patients on stable treatment with a VKA (i.e. continuously over the previous 12 months) (n=2102) or recently switched (within 12 months) from a VKA to a NOAC (n=213) during a 1-year follow-up, allowing a snapshot of factors influencing the switch at a time when NOACs were being introduced into the market. RESULTS: Compared to patients on stable treatment with a VKA, switched patients were similar in terms of age, sex, body mass index and other risk factors, but had lower prevalences of hypertension and heart valve dysfunction, and a lower rate of use of concomitant treatment with antiplatelet/anti-inflammatory agents; they also had a lower CHA2DS2-VASc score. Among 25 features investigated, switched patients more often reported bruising or bleeding, complained about bruising, were dissatisfied with the anticoagulant treatment, and reported mobility problems and anxiety/depressive traits. CONCLUSIONS: At the beginning of NOAC prescriptions, European doctors tended to switch from VKAs to NOACs those patients at lower risk than "non-switchers". Complaints about bruising or bleeding, dissatisfaction with treatment, mobility problems and anxiety/depression traits appear to be related to - and may have influenced - the choice to switch from a VKA to a NOAC.

ADC changes in schizophrenia: a diffusion-weighted imaging study.

Studies using diffusion tensor imaging (DTI) have shown multifocal reduction in anisotropy of white matter fibre tracts in schizophrenia, and a few of these also suggest changes in apparent diffusion coefficient (ADC). In this study, we assessed ADC in 18 patients with schizophrenia and 18 healthy controls using a voxel-based approach. We did not find evidence of statistically significant changes in ADC in either direction at P < 0.05 (FDR corrected) using different smoothing filter sizes; only at an uncorrected threshold of P < 0.001 did we find an increase in a small right prefrontal area close to our previous FA finding. Our findings therefore do not support ADC changes to be a marker of white matter or grey matter abnormalities in schizophrenia. Changes in other parameters like fractional anisotropy (FA) might be a more sensitive indicator of white matter pathology in this disorder.

CD163 expression is present in cutaneous histiocytomas but not in atypical fibroxanthomas.

CD163, a hemoglobin scavenger receptor, is expressed in monocytes and macrophages. Recent work has shown that this marker is specific for neoplasms of histiocytic differentiation. Our aim was to test the ability of CD163 to separate cutaneous histiocytomas from their morphologic mimics. We tested the expression of CD163 in 78 cases, including 19 xanthogranulomas, 16 atypical fibroxanthomas, 6 reticulohistiocytomas, 8 epithelioid cell histiocytomas, 9 cases of Langerhans cell histiocytosis, 10 xanthomas, and 10 intradermal Spitz nevi. CD163 expression was seen in all xanthogranulomas and reticulohistiocytomas, 4 epithelioid cell histiocytomas, 2 cases of Langerhans cell histiocytosis, and 8 xanthomas but was absent in atypical fibroxanthomas and Spitz nevi. CD163 is an excellent marker for confirming histiocytic differentiation and is useful in eliminating morphologic mimics such as Spitz nevi from the differential diagnosis. The lack of CD163 in atypical fibroxanthomas argues against a histiocytic origin for this tumor.

Combined use of PCR-based TCRG and TCRB clonality tests on paraffin-embedded skin tissue in the differential diagnosis of mycosis fungoides and inflammatory dermatoses.

The distinction between mycosis fungoides (MF) and inflammatory dermatoses (ID) by clinicopathologic criteria can be challenging. There is limited information regarding the performance characteristics and utility of TCRG and TCRB clonality assays in diagnosis of MF and ID from paraffin-embedded tissue sections. In this study, PCR tests were performed with both TCRG and TCRB BIOMED-2 clonality methods followed by capillary electrophoresis and Genescan analysis using DNA samples from 35 MF and 96 ID patients with 69 and 133 paraffin-embedded specimens, respectively. Performance characteristics were determined for each test individually and in combination. TCRG and TCRB tests demonstrated identical sensitivity (64%) and specificity (84%) when analyzed as individual assays. The positive predictive value, negative predictive value, and change of posttest MF probability over a range of MF pretest probabilities were obtained. These data were used to construct an algorithm for sequential use of TCRG and TCRB. As single tests, commercially available BIOMED-2 PCR-based TCRG and TCRB clonality tests on paraffin-embedded tissue have no significant difference in terms of sensitivity and specificity. Combined use of the two tests in patients with intermediate pretest probabilities as proposed in the algorithm could improve test utility.

Prognostic factors in primary cutaneous anaplastic large cell lymphoma: characterization of clinical subset with worse outcome.

OBJECTIVES: To identify prognostic factors in primary cutaneous anaplastic large cell lymphoma (pcALCL), focusing on extensive limb disease (ELD), defined as initial presentation or progression to multiple skin tumors in 1 limb or contiguous body regions, and to study gene expression profiles of patients with pcALCL. DESIGN: Retrospective cohort study. SETTING: The Stanford Comprehensive Cancer Center and dermatology ambulatory clinics. PATIENTS: A total of 48 patients with pcALCL evaluated from 1990 through 2005. MAIN OUTCOME MEASURES: Hazard ratios (HRs) for prognostic factors for overall survival (OS) and disease-specific survival (DSS) and risk factors for progression to extracutaneous disease were identified using Cox regression. Gene expression profiles of 9 typical pcALCL and 3 ELD samples were investigated using complementary DNA microarrays. RESULTS: Univariate analysis demonstrated age, ELD, and progression to extracutaneous disease as significant prognostic factors for OS, whereas ELD and progression to extracutaneous disease were significant for DSS. In multivariate analysis, age (HR, 1.83; 95% confidence interval [CI], 1.02-3.26) and progression to extracutaneous disease (HR, 6.42; 95% CI, 1.39-29.68) remained significant for OS, whereas ELD (HR, 29.31; 95% CI, 1.72-500.82) and progression to extracutaneous disease (HR, 13.12; 95% CI, 1.03-167.96) remained independent prognostic factors for DSS. Presentation with T3 disease was a risk factor for progression to extracutaneous disease (HR, 10.20; 95% CI, 1.84-56.72). Microarray data revealed that patients with ELD and typical pcALCL formed distinct clusters. CONCLUSIONS: Patients with ELD have a more aggressive course associated with a differential gene expression profile. More aggressive treatments may be indicated for patients with ELD and those whose disease progresses to extracutaneous disease because they have poorer outcomes.

Evaluation of B-cell clonality using the BIOMED-2 PCR method effectively distinguishes cutaneous B-cell lymphoma from benign lymphoid infiltrates.

Primary cutaneous B-cell lymphomas (CBCL) are a diverse group of lymphomas that are limited to the skin at the time of diagnosis. Recently, standardized polymerase chain reaction protocols for immunoglobulin (Ig) rearrangement in nodal malignancies using the BIOMED-2 method have been studied extensively. However, reports of investigations of Ig clonality in CBCL using the BIOMED-2 method have been scant. We hypothesized that clonality detection in CBCL with the BIOMED-2 method could effectively distinguish malignant from benign B-cell-rich infiltrates in the skin. Formalin-fixed tissue samples from 26 patients with CBCL and 23 with benign lymphoid infiltrates were analyzed for Ig clonality using standardized BIOMED-2 polymerase chain reaction protocols. The (14;18) translocation was also assessed. A clone was detected in 22 (85%) of the 26 patients with CBCL [12/15 (80%) marginal zone B-cell lymphoma; 10/11 (91%) follicle center lymphoma] and in 1 (4%) of the 23 patients with benign infiltrates. The (14;18) translocation was present in 3 (12%) of the 26 patients with CBCL [1/15 (7%) marginal zone B-cell lymphoma; 2/11 (18%) follicle center lymphoma]. Our preliminary data indicate that Ig clonality can be detected in formalin-fixed samples of CBCL with meaningful sensitivity (85%) and high specificity (96%) using the BIOMED-2 method. This study forms the basis for further investigating the role of Ig clonality in distinguishing CBCL from benign lymphoid infiltrates that may pose a challenge in morphologic diagnosis.

Clinicopathologic features and treatment outcomes in Woringer-Kolopp disease.

Woringer-Kolopp disease, also known as pagetoid reticulosis, is an exceedingly rare variant of mycosis fungoides. Accurate diagnosis and effective treatment is essential to prevent progression to debilitating disease. We identified 7 patients with Woringer-Kolopp disease treated at our institution. We review the major clinical and pathologic characteristics of this disease, focusing on treatment strategies and patient outcomes. All of our patients were successfully treated with skin-directed therapies including topical steroids, topical nitrogen mustard, psoralen plus ultraviolet A, narrow-band ultraviolet B, and radiation therapy. Our observations confirm that Woringer-Kolopp disease carries an excellent prognosis, and support that the most effective and appropriate treatment for recalcitrant or severe Woringer-Kolopp disease is localized radiation therapy.

Reactive eccrine syringofibroadenoma arising in peristomal skin: An unusual presentation of a rare lesion.

We report the third case of eccrine syringofibroadenoma (ESFA) arising in peristomal skin. A 55-year-old man presented with a 15- x 10-cm pale pink verrucous, exophytic, intermittently tender plaque involving his ileostomy site. He had undergone proctocolectomy with ileostomy creation 33 years prior for ulcerative colitis. The clinical differential diagnosis included granulomatous dermatitis, infection (fungus or atypical mycobacterium), or neoplasm. A punch biopsy specimen was performed and showed ESFA. Although ESFA is considered to be benign, recent reports have demonstrated an association of ESFA with malignancy or malignant transformation of ESFA. Furthermore, ESFA and reported cases of ileostomy carcinoma share similar clinical symptoms at presentation including pain, irritation, ulceration, bleeding, and the presence of a fungating mass. The lesion was, therefore, excised in toto and the excisional specimen showed no evidence of malignancy. We speculate that ESFA is a reaction to chronic irritation and, analogous to other long-standing reactive processes such as lichen sclerosis or burn scar ulcers, may be associated with malignant transformation. Because of this possibility and the clinical overlap with ileostomy carcinoma, peristomal ESFA should be treated with complete excision. If it is not amenable to complete excision because of lesion size or anatomic complexity, generous sampling and close clinical follow-up are recommended.

Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma.

The classification of primary cutaneous large B-cell lymphoma (PCLBCL) is based on standard morphology, immunohistochemistry, and clinical presentation. There are two major subtypes in the current WHO-EORTC classification: follicle center lymphoma and diffuse large B-cell lymphoma, leg-type (DLBCL-LT). The goals of this study were to examine a series of DLBCLs to determine (1) whether the immunohistochemical paradigm of germinal center B-cell and non-germinal center B-cell types of systemic DLBCL could be applied to PCLBCL; (2) whether application of the newly described germinal center B-cell marker, human germinal center-associated lymphoma (HGAL) also discriminates between these types as a further support for germinal center B-cell origin for primary cutaneous center lymphoma; and (3) whether any of these biologic markers were of prognostic significance. To this end, 32 cases of diffuse PCLBCL (22 primary cutaneous follicular center lymphomas and 10 DLBCL-LT) were classified based on the WHO-EORTC criteria and studied for expression of CD20, BCL2, BCL6, CD10, MUM-1, and HGAL by immunohistochemistry. Results were correlated with clinical features. HGAL and BCL6 expression and germinal center B-cell phenotype were associated with primary cutaneous follicular center lymphoma. The combination of HGAL and BCL6 positivity had the highest sensitivity (88%) and specificity (100%) for predicting subtype compared to either marker alone. Both HGAL and BCL6 were associated with the germinal center B-cell phenotype. The correlation of HGAL expression with the germinal center B-cell phenotype demonstrates the role of this marker in the classification of cutaneous large B-cell lymphomas. BCL6 expression was the only immunohistochemical marker associated with overall survival. Characterizing PCLBCLs with markers of B-cell maturation stage is a useful framework for studying, classifying, and clinically stratifying these lymphomas.

Palisaded neutrophilic and granulomatous dermatitis associated with limited systemic sclerosis.

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a condition that is characterized histopathologically by a characteristic pattern of granulomatous inflammation in the presence or absence of leukocytoclastic vasculitis. It has been associated with systemic diseases, especially autoimmune conditions such as rheumatoid arthritis and Behçet's disease. A 44-year-old woman with underlying limited systemic sclerosis presented with painful erythematous nodules located on her face and scalp. Histopathologic analysis confirmed a diagnosis of PNGD, which self-resolved within weeks of the biopsy. To our knowledge, this is the first report of a case of PNGD associated with systemic sclerosis. A review of the literature revealed that PNGD is a female-predominant disease that is most commonly associated with rheumatoid arthritis, followed closely by lupus erythematosus. Most patients with PNGD respond to treatment of the underlying systemic disease, although spontaneous resolution is not uncommonly observed.