Causes of hypereosinophilia in 100 consecutive patients.

BACKGROUND: Hypereosinophilia (HE, persistent peripheral blood eosinophilia > 1.5 × 109 /L) and hypereosinophilic syndrome (HES, HE with end-organ damage) are classified as primary (due to a myeloid clone), secondary (due to a wide variety of reactive causes), or idiopathic. Diagnostic evaluation of eosinophilia is challenging, in part because secondary causes of HE/HES such as lymphocyte-variant HES (L-HES) and vasculitis are difficult to diagnose, and emerging causes such as immunoglobulin G4-related disease (IgG4-RD) have rarely been examined. OBJECTIVE AND METHODS: We reviewed 100 consecutive patients with HE/HES who underwent extensive evaluation for primary and secondary eosinophilia at a single tertiary care center to determine causes of HE/HES in a modern context. RESULTS: Six patients had primary HE/HES, 80 had a discrete secondary cause identified, and 14 had idiopathic HE/HES. The most common causes of secondary eosinophilia were L-HES/HES of unknown significance (L-HESus) (20), IgG4-RD (9), and eosinophilic granulomatosis with polyangiitis (EGPA) (8). CONCLUSIONS: In contrast to other large published series of HE/HES, most patients in this study were found to have a discrete secondary cause of eosinophilia and only 14 were deemed idiopathic. These findings highlight the importance of extensive evaluation for secondary causes of eosinophilia such as L-HES, IgG4-RD, and EGPA.

Red cell distribution width and neutrophil-lymphocyte ratio in rheumatoid arthritis.

Red cell distribution width (RDW) and neutrophil-lymphocyte ratio (NLR) are potential low-cost markers for detecting rheumatoid arthritis (RA) disease activity, but evidence on their accuracy for this purpose is conflicting. We aimed to determine the relationship between these and the Disease Activity Score of 28 joints (DAS-28) among Filipino RA patients, and to evaluate their ability to discriminate between patients with active RA and those in remission. This was a cross-sectional study done through a 7-year review of medical records of 134 adult patients with RA in a tertiary government hospital. Correlations were analyzed using Spearman analysis, and the receiver operating characteristic (ROC) curve was used to derive the sensitivity, specificity, and optimal cut-off values of RDW and NLR. Most patients were females with a mean disease duration of 7 years. Eighty-one percent (81%) had active disease using DAS-28 ESR. A weak positive correlation was found between NLR and DAS-28 and between NLR and ESR, but RDW did not correlate with either DAS-28 or ESR. The ROC analysis showed that in the differentiation of active RA and inactive RA, both RDW (area under the curve [AUC] 0.516, cut-off of ≥ 14.2% with 55.6% sensitivity and 42.3% specificity) and NLR (AUC 0.629, cut-off of ≥ 2.32 with 54.6% sensitivity and 76.9% specificity) had poor performance. NLR, but not RDW, was positively but weakly correlated with DAS-28 and ESR, making it a helpful marker of disease activity and inflammation in RA. Both NLR and RDW had low sensitivity and specificity for active RA and may not be useful in detecting disease activity.

Convalescent Plasma as Adjunctive Therapy for Hospitalized Patients with COVID-19: The Co-CLARITY Trial.

Background and Objective: Convalescent plasma therapy (CPT) may reduce the risk of disease progression among patients with COVID-19. This study was undertaken to evaluate the efficacy and safety of CPT in preventing ICU admission among hospitalized COVID-19 patients. Methods: In this open-label randomized controlled trial, we randomly assigned hospitalized adult patients with COVID-19 in a 1:1 ratio to receive convalescent plasma as an adjunct to standard of care or standard of care alone. The primary endpoint was ICU admission within first 28 days of enrolment. Primary safety endpoints include rapid deterioration of respiratory or clinical status within four hours of convalescent plasma transfusion and cumulative incidence of serious adverse events during the study period including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), severe allergic reactions, and transfusion-related infections. Results: A total of 22 patients were assigned to receive convalescent plasma as an adjunct to standard of care and 22 to receive standard of care alone. The median time from onset of COVID-19 symptoms to study enrolment was eight days (IQR, 4 to 10). Two patients (9.1%) in the CPT group and one patient (4.5%) in the control group were admitted to the ICU. The primary outcome measure, ICU admission, was not different between the two groups (q-value >0.9). No patient who received convalescent plasma had rapid deterioration of respiratory/clinical status within four hours of transfusion and none developed TRALI, TACO, anaphylaxis, severe allergic reactions, or transfusion-related infections. There was also no significant difference in the secondary outcomes of 28-day mortality (two patients in the CPT group and none in the control group, q-value >0.90), dialysis-free days, vasopressor-free days, and ICU-free days. Conclusions: Among hospitalized COVID-19 patients, no significant differences were observed in the need for ICU admission between patients given CPT as adjunct to standard of care and those who received standard of care alone. Interpretation is limited by early termination of the trial which may have been underpowered to detect a clinically important difference.

A 54-Year-Old Woman with Cutaneous Nodules.

A 54-Year-Old Woman with Cutaneous NodulesA 54-year-old woman presented with chronic cutaneous nodules and plaques. How do you approach the evaluation, and what is the diagnosis?

IgG4 plasma cell myeloma without clinical evidence of IgG4-related disease: a report of two cases.

Background: Serum IgG4 is typically measured to investigate for Immunoglobulin G4-related Disease (IgG4-RD), a fibroinflammatory condition associated with polyclonal increase in serum IgG4. However, increased IgG4 can also be monoclonal, and little is known about IgG4 myeloma. Methods: We describe two cases of IgG4 myeloma without clinical, radiologic, or laboratory features of IgG4-related disease. Results: An 84 year old man presented with anemia and compression fractures and a 77 year old man presented with anemia, hypercalcemia and renal failure. Both had markedly elevated monoclonal serum IgG4, 34 g/L and 48 g/L in the beta region, and increased IgG positive bone marrow plasma cells, 50% and 80%, respectively. Neither had clinical or radiological manifestations of IgG4-related disease (IgG4-RD) such as salivary or lacrimal gland swelling, autoimmune pancreatitis , or retroperitoneal fibrosis. Both cases responded well to standard myeloma therapy. The IgG4 paraprotein caused spuriously elevated beta-2 microglobulin of 45.2 mg/L in case two due to interference with the assay. Conclusion: These cases illustrate the importance of performing serum protein electrophoresis in tandem with IgG subclasses to distinguish between polyclonal and monoclonal increases in serum IgG4. The lack of typical IgG4-RD features in these two patients suggests that monoclonal elevation in serum IgG4 alone is insufficient to cause the organ damage characteristic of IgG4-RD. Larger studies of IgG myeloma subtypes are warranted to explore whether IgG1, IgG2, IgG3 and IgG4 myeloma differ in natural history and whether the interference with beta-2 microglobulin is specific to IgG4 monoclonal proteins.

Clinical utility of serum IgG4 measurement.

This article will review the structure and function of IgG4, methods of measuring serum IgG4 concentrations, clinical conditions associated with increased and decreased serum IgG4, and the test characteristics of serum IgG4 in the diagnosis and management of Immunoglobulin G4-Related Disease (IgG4-RD). The four subclasses of IgG were discovered in 1964 through experiments on monoclonal IgG in patients with myeloma. Since 2001, interest in measuring serum IgG subclasses has increased dramatically due to the emergence of IgG4-RD, a multisystem fibroinflammatory condition wherein polyclonal serum IgG4 concentration is increased in approximately 70% of cases. Increased serum IgG4 typically manifests as a restriction in the anodal gamma region on serum protein electrophoresis, often with beta-gamma bridging, and can be mistaken as a monoclonal protein or polyclonal increase in IgA. Limitations of current clinical methods used in quantitation of serum IgG4 concentrations will be discussed, including the common immunonephelometric assays and LC-MS/MS based assays. Polyclonal IgG4 elevation is not specific for IgG4-RD, and may also occur in conditions such as eosinophilic granulomatosis with polyangiitis (EGPA), lymphoma, and multicentric Castleman disease (MCD). Race and gender differences also affect interpretation of serum IgG4 concentrations, for instance Asians have a higher serum IgG4 concentration than Whites and males have a higher concentration than females.

Autoimmune-Associated Hemophagocytosis and Myelofibrosis in a Newly Diagnosed Lupus Patient: Case Report and Literature Review.

Bone marrow abnormalities in SLE are now becoming increasingly recognized, suggesting that the bone marrow may also be an important site of target organ damage. In this study, we present a rare case of concurrent autoimmune hemophagocytic syndrome and autoimmune myelofibrosis, potentially life-threatening conditions, in a newly diagnosed SLE patient. We report a case of a 30-year-old Filipino woman who presented with a one-year history of fever, constitutional symptoms, exertional dyspnea, joint pains, and alopecia and physical examination findings of fever, facial flushing, cervical lymphadenopathies, and knee joint effusions. Laboratory workup revealed pancytopenia with leukoerythroblastosis, elevated ESR, increased serum levels of transaminases, elevated CRP and LDH, hyperferritinemia, hypertriglyceridemia, proteinuria, hepatomegaly, and positive antinuclear antibody. Bone marrow aspiration and trephine biopsy revealed hemophagocytosis and moderate myelofibrosis. The patient was diagnosed with SLE with concomitant autoimmune-associated hemophagocytic syndrome and autoimmune myelofibrosis. Treatment with high-dose corticosteroids led to dramatic clinical improvement with normalization of laboratory data and complete resolution of bone marrow hemophagocytosis and myelofibrosis. Hemophagocytosis and myelofibrosis, although uncommon, are possible initial manifestations of SLE and should be included in the differential diagnosis of cytopenias in SLE. Thorough clinical assessment and microscopic bone marrow examination and timely initiation of corticosteroid therapy are essential in the diagnosis and management of these potentially life-threatening conditions. This case emphasizes that the bone marrow is an important site of target organ damage in SLE, and evaluation of cytopenias in SLE should take this into consideration.

Seizure and Acute Vision Loss in a Filipino Lupus Patient: A Case of Posterior Reversible Encephalopathy Syndrome with Intraparenchymal Hemorrhage.

Posterior reversible encephalopathy syndrome (PRES) is a rare and poorly understood neurologic condition that has been described in some patients with systemic lupus erythematosus (SLE). Intracerebral hemorrhage is a unique and atypical presentation of PRES and has been described only in a small number of patients with SLE. We present the case of a 33-year-old female, diagnosed with SLE and active nephritis, who was admitted for seizures. She had acute-onset headache, confusion, and bilateral vision loss associated with severe hypertension. CT scan revealed right occipital and parietal lobe hemorrhage. MRI showed vasogenic edema and hyperintense foci in bilateral cortical and subcortical regions of the occipital and posterior parietal lobes which are consistent with posterior reversible encephalopathy syndrome (PRES). Strict blood pressure control and medical ICP-lowering treatment were immediately instituted, while maintaining her on anticonvulsants, high-dose steroids, and mycophenolate mofetil. The patient was discharged with improvement in vision and resolution of headache. On follow-up, she had gained her premorbid visual acuity and reported no recurrence of headache or seizures. Despite its name, reversibility remains to be conditional in PRES. A high index of suspicion is important, especially among those who present with seizure, headache, and visual loss. Early diagnosis and timely initiation of therapy is recommended, as clinical symptoms are potentially reversible and delayed therapy may result in life-threatening complications, such as coma or death.