Lymphocytic Variant Of Hypereosinophilic Syndrome Research Articles

Lymphocytic variant of hypereosinophilic syndrome: Diagnostic challenge

T-cell phenotyping by flow cytometry and PCR analysis of TCR gene rearrangement patterns, are necessary to assess the diagnosis of Lymphocytic variant of Hypereosinophilic Syndrome (L-HES). The aim of this study was to evaluate the diagnostic contribution of flow cytometry using a single panel.

Hematological Neoplasms with Eosinophilia.

Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 × 109/L. A count above 0.5 × 109/L is considered to indicate eosinophilia, while a count equal to or above 1.5 × 109/L is defined as hypereosinophilia. In bone marrow aspirate, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non-hematologic, whether they are non-neoplastic (allergic diseases, drugs, infections, or immunological diseases) or neoplastic (solid tumors). Eosinophilia that is associated with a hematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphocytic variant of hypereosinophilic syndrome, and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia that is associated with a hematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with its origin in stem cells (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with core binding factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive or clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of hematological malignancies with eosinophilia.

The Phase 3 Natron Study Evaluating Benralizumab in Patients with Hypereosinophilic Syndrome: Study Design and Patient Characteristics

Background and Significance: Hypereosinophilic syndrome (HES) is a rare, heterogeneous disorder defined by blood eosinophilia (absolute eosinophil count [AEC] >1500 cells/μL) on 2 examinations ≥1 month apart and eosinophil-mediated end-organ involvement, including dermatologic, pulmonary, gastrointestinal, and/or cardiovascular manifestations. Symptoms and health-related quality of life vary depending on the organ systems involved. HES is often treated with corticosteroids and other immunosuppressants. However, long-term use of these agents is associated with decreased efficacy and significant toxicity. Whereas anti-IL-5 antibody mepolizumab was recently approved for the treatment of HES (Roufosse, et al. J Allergy Clin Immunol. 2020;146(6):1397-1405), response is not universal and additional targeted agents are clearly warranted. Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor α monoclonal antibody that induces rapid, near-complete depletion of eosinophils through antibody-dependent, cell-mediated cytotoxicity. It is currently approved for use in patients with severe eosinophilic asthma and has demonstrated AEC-reducing effects in patients with HES (Kuang, et al. N Engl J Med. 2019;380(14):1336-46). Study Design and Methods:This phase 3, multicenter, randomized, double-blind (DB), placebo-controlled study (NATRON; NCT04191304) evaluating the efficacy of benralizumab versus placebo will enroll ~120 patients with documented HES (Figure 1A). Recruitment will stop after approximately 38 patients have had their first HES worsening/flare during the DB period, at which point the data cutoff for the primary analysis will occur. Eligible patients are ≥12 years of age with an AEC ≥1000 cells/mL at screening, have active signs/symptoms of an HES worsening/flare or a history of ≥2 HES worsening/flares within 12 months before enrollment, and have a stable treatment regimen (≥4 weeks). Patients must be FIP1L1-PDGFRA-negative and corticosteroid-responsive, defined as an AEC of <1000 cells/μL after 2 days of corticosteroid treatment. The primary endpoint is time to first HES worsening/flare during the DB period. Key secondary endpoints during the DB period include the proportion of patients who experience HES worsening/flare events, the number of HES worsening/flare events (annualized rate/year), time to first hematologic relapse, and change from baseline in fatigue at week 24 as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a. Patients who complete the 24-week DB treatment period will continue with active treatment in a ≥52-week open-label extension. We present the study design and interim baseline characteristics of patients recruited to date. Results:As of the June 6, 2023, cutoff date, 87 patients were enrolled in the full analysis set (Figure 1B). Among these patients, the mean (SD) age was 48.4 (17.79) years, 64.4% were female, and 84.3% were White. The mean (SD) time since the first appearance of HES symptoms and since HES diagnosis was 8.14 (8.12) and 4.87 (6.54) years, respectively. The proportion of patients with the lymphocytic variant HES was 14.9%. The most common primary organs involved were the lungs (35.6%), followed by the skin (25.3%) and the gastrointestinal tract (21.8%). Thirty-four (39.1%) and 32 (36.8%) patients experienced 2 and ≥3 HES worsening/flare events in the previous 12 months, respectively. The mean (SD) PROMIS Fatigue T-score was 55.0 (9.42). Mean (SD) baseline eosinophil levels were 1960 (2610) cells/µL, with median (interquartile range) levels of 1120 (60, 20910) cells/µL. Conclusions: Results from the NATRON study will provide insight into whether benralizumab is beneficial in addition to background therapy in patients with FIP1L1-PDGFRA-negative steroid-responsive HES. Funding: This study is funded by AstraZeneca (Gothenburg, Sweden). This work is funded in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Acknowledgments:Vivian H. Shih, Dianne Griffis, Himanshu Parikh, Ron A. Chen, Ying Fan, Gaëll Mayer, Rohit Katial, and Ioannis Psallidas.

T-cell chronic active EBV diagnosed in a 65-year-old male presenting as idiopathic hypereosinophilic syndrome

A 65-year-old male from Nigeria, admitted with dehydration and painful oral ulcers, is seen by allergy/immunology for hypereosinophilia.The patient had idiopathic eosinophilia (mean 5,000 cells/uL) ongoing for nine years. There were no evident drug or infectious causes. The eosinophilia peaked at 28,000 cells/µL, accompanied by parotid swelling, pustular skin rash, and elevated serum-IgG4 level (400 mg/dL). Rheumatology evaluated for IgG4-related disease and hypereosinophilic syndrome. This work-up demonstrated elevated IgE (39,000 IU/mL) and tryptase (40 ng/mL) levels. Bone marrow biopsy showed a hypercellular marrow with erythroid hyperplasia and eosinophilia. Submandibular gland, skin, and excisional lymph node biopsies demonstrated IgGsecreting plasma cells, lymphocytic/eosinophilic infiltrates, and lymphoid hyperplasia, respectively. All biopsies stained negative for IgG4. Treatment for idiopathic hypereosinophilia was initiated with corticosteroids, rituximab, and mycophenolate mofetil (MMF). Symptomatic improvement was attained on MMF (1000 mg twice daily) with the addition of mepolizumab (300 mg every 4 weeks).He unfortunately progressed to high fevers with elevated ferritin (7,286 ug/L) and soluble IL-2Ra (31,276.7 pg/mL) levels. He did not meet full criteria for hemophagocytic lymphohistiocytosis and improved after corticosteroids. EBV PCR from blood was >220,000 IU/mL.Dedicated immune work-up showed a non-specific population of lymphocyte-like cells without clear lineage markers (CD2dim/- surface CD3-CD4-CD8-CD7-CD56-CD49d-CD294dim) on peripheral blood flow cytometry, with otherwise normal T, B, and NK cell enumeration. There was reduced cytotoxic killing function of CD8+ T cells and NK cells by chromium-51 release assay. Sorted peripheral blood mononuclear cells demonstrated positive EBV viral load in B cells (1,018,239 IU/mL), T cells (857,418 IU/mL),NK cells (237,459), and myeloid cells (532,641 IU/mL). EBV-encoded RNA was positive within lymph node T cells, most consistent with a diagnosis of T-cell CA-EBV. The Invitae 407 gene immunodeficiency panel was sent; however, a pathogenic variant was not identified. The patient was seen by hematology/oncology with plans for hematopoietic stem cell transplant. Unfortunately, he succumbed to complications from CA-EBV and multiorgan failure.We describe a male with lymphocytic-variant hypereosinophilic syndrome and a longstanding constellation of inflammatory and lymphoproliferative symptoms due to CA-EBV. His course initially eluded his care team and only after careful multidisciplinary discussion was a diagnosis reached.

JAK inhibition for CD3− CD4+ lymphocytic-variant hypereosinophilic syndrome

Alternatives are urgently needed in patients with CD3− CD4+ lymphocytic-variant hypereosinophilic syndrome (L-HES) requiring high-level steroids or who are unresponsive and/or intolerant to conventional alternative therapies. We report five L-HES patients (44–66 years) with cutaneous involvement (n = 5) and persistent eosinophilia (n = 3) despite conventional therapies, who successfully received JAK inhibitors (tofacitinib n = 1, ruxolitinib n = 4). JAKi led to complete clinical remission in the first 3 months in all (with prednisone withdrawal in four). Absolute eosinophil counts normalized in cases receiving ruxolitinib, while reduction was partial under tofacitinib. After switch from tofacitinib to ruxolitinib, complete clinical response persisted despite prednisone withdrawal. The clone size remained stable in all patients. After 3–13 months of follow-up, no adverse event was reported. Prospective clinical trials are warranted to examine the use of JAKi in L-HES.

What we have learned about lymphocytic variant hypereosinophilic syndrome: A systematic literature review

Lymphocytic variant is a rare subtype of hypereosinophilic syndrome (L-HES) secondary to overproduction of eosinophilopoietic cytokines by the underlying clonal T lymphocytes with abnormal immunophenotypes. Clinical profiles, treatment responses, and outcomes of L-HES are not well characterized given its rarity. We performed a systematic literature review to summarize cases identified in PubMed and Embase databases between January 1994 and July 2021. A total of 148 patients met the inclusion criteria with a median age at diagnosis of 46 years and 51.4% being male. Cutaneous manifestations (81.1%) predominated the clinical picture, while the characteristic cardiovascular involvement was seen in 11.5% of cases. The median eosinophil count at baseline was 5.3 × 109/L and 109 patients (73.6%) had underlying clonal T lymphocytes harboring the classic CD3−CD4+ immunophenotype, which was associated with higher numbers of eosinophils and organ involvement at baseline. Corticosteroids were the most common first-line agent (88.1%), but most patients required additional treatment, leading to clinical or hematologic response in two-thirds. The 10-year overall survival was 81.6% (95% confidence interval [CI] 68.1–89.8). Transformation into malignant T cell lymphoma was observed in 19 patients, specifically in those with cardiovascular involvement (odds ratio [OR] 4.723, 95% CI 1.304–17.108, p = 0.018) and imatinib use (OR 4.284, 95% CI 1.191–15.404, p = 0.026). Taken together, a heavier disease burden was shown in L-HES patients with classic CD3−CD4+ lymphocytes but they were manageable with corticosteroids and sparing agents. There is an increased risk of lymphoma transformation that could be associated with certain clinical surrogates.

27660 Parasite infection in a patient with a CD30 clonal T-cell lymphocytic variant of hypereosinophilic syndrome: Cause or coincidence

Hypereosinophilic syndromes (HES) are defined by the presence of blood and/or tissue hypereosinophilia producing organ damage. HES can arise from a primary (neoplastic) growth of eosinophils or a reactive proliferation of eosinophils secondary to parasitic infestations, inflammatory diseases or neoplasms. A lymphocytic variant (L-HES) has been recently described in which a clonal T-cell population releasing Th2-related cytokines induce eosinophil proliferation. Cutaneous lesions in HES are frequent and nonspecific. A 65-year-old Dominican male presented with a progressive generalized rash and dyspnea for 2 years. A skin biopsy was performed, showing an unspecific spongiotic dermatitis. Blood tests revealed eosinophilia (6.4ˆ3/uL) and IgE 1.050 UI/mL. Strongyloides stercolaris, Schistosoma mansoni, and Hymenolepsis nana were detected in the stool. Antiparasitic treatment was carried out and stool parasites were no longer detectable. However, both the dyspnea and the skin rash progressed. Hyperesosinophilia persisted. A CT scan and a lung biopsy confirmed an eosinophilic pneumonia. A new cutaneous specimen showed a perivascular and interstistitial infiltrated composed of eosinophils and atypical CD30+ T cells. Bone marrow biopsy was normal. Clonality of T-cell receptor was detected in peripheral blood. Brentuximab and meplizumab were introduced with rash and dyspnea improvement. Herein, we present a case of HES in which a parasite infestation was first diagnosed and correctly treated, yet without resolution of the symptoms. The subsequent hematologic investigations and skin biopsy revealed the presence of a clonal, atypical T cell proliferation consistent with the diagnosis of a L-HES. To our knowledge, this coincidence has not previously described.

Treatment of lymphocyte-variant hypereosinophilic syndrome (L-HES): what to consider after confirming the elusive diagnosis.

Lymphocyte-variant hypereosinophilic syndrome (L-HES) is a rare disease driven by immunophenotypically aberrant T cells producing eosinophilopoetic cytokines such as interleukin-5 (IL-5). Treatment is challenging because L-HES is relatively steroid resistant and not amenable to tyrosine kinase inhibitors. We searched the literature for clinical trials and observational studies, including case reports, of patients treated for L-HES. In all, 25 studies were selected; two were randomised controlled trials of IL-5 blockade, which included some patients with L-HES, and the rest were observational studies. Corticosteroids are often used as first-line therapy, but patients with L-HES have lower response rates than other types of HES. Treatments that reduce symptoms and steroid dependence in some patients include interferon-alpha (IFN-α), anti-IL-5 monoclonal antibodies, cyclosporine and mycophenolate. These drugs target T-cell activation and proliferation, or IL-5 directly. Although effective, IFN-α and cyclosporine were commonly reported to cause side-effects resulting in discontinuation. Alemtuzumab can induce remissions, but these are generally short lived. The anti-IL-5 monoclonal antibodies mepolizumab and benralizumab are effective and well tolerated, but with a high rate of relapse once withdrawn. Hydroxyurea, methotrexate, imatinib were unsuccessful in most patients studied. More prospective clinical trials are needed for patients with L-HES.

CD3−CD4+ Lymphocytic Variant Hypereosinophilic Syndrome: Diagnostic Tools Revisited

Identification of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) is challenging, and has important prognostic and therapeutic implications. This study was undertaken to assess diagnostic tools for L-HES and to develop evidence-based diagnostic recommendations. Biomarkers of T-cell-driven disease were compared between patients with L-HES versus idiopathic HES (I-HES) variants. Those performed routinely (serum immunoglobulin levels, T-cell phenotyping, T-cell receptor [TCR] gene rearrangement patterns) were collected from medical files, whereas others were prospectively assessed on stored blood samples (serum CCL17/thymus and activation regulated chemokine [TARC] levels, invitro cytokine production). This study included 48 patients with I-HES and 20 with L-HES associated with a CD3-CD4+ T-cell subset, including 7 with less than 5% aberrant cells. Neither increased serum immunoglobulin levels nor clonal TCR gene rearrangements were sufficiently sensitive or specific for L-HES. In contrast, systematically enhanced expression of the T-cell surface antigens CD2, CD5, CD45RO, and CD95 by these cells allowed for accurate detection by flow cytometry. Serum CCL17/TARC levels were significantly higher in patients with L-HES compared with those with I-HES, and a threshold of 3000 pg/mL allowed for detection of all subjects with L-HES with 75% specificity. Quantification of intracytoplasmic cytokine production by flow cytometry is the most reliable method for detection of enhanced type 2 cytokine expression, most notably for IL-4 and IL-13. Adapting the standard of procedure for T-cell phenotyping in patients with unexplained hypereosinophilia is currently the most reliable means of identifying those with CD3-CD4+ L-HES.

A case of lymphocytic variant hypereosinophilic syndrome in an elderly patient

A case of lymphocytic variant hypereosinophilic syndrome in an elderly patient

Reactive Eosinophil Proliferations in Tissue and the Lymphocytic Variant of Hypereosinophilic Syndrome.

The 2019 Society for Hematopathology and European Association for Haematopathology Workshop reviewed the spectrum of neoplastic, nonneoplastic, and borderline entities associated with reactive eosinophilia in tissue. The workshop panel reviewed 46 cases covered in 2 workshop sessions. The 46 cases were presented with their consensus diagnoses during the workshop. Reactive eosinophilia in lymph nodes and other tissues may be accompanied by or be distinct from peripheral blood eosinophilia. Reactive etiologies included inflammatory disorders such as Kimura disease and IgG4-related disease, which may show overlapping pathologic features and reactions to infectious agents and hypersensitivity (covered in a separate review). Hodgkin, T-cell, and B-cell lymphomas and histiocytic neoplasms can result in reactive eosinophilia. The spectrum of these diseases is discussed and illustrated through representative cases. Reactive eosinophilia in lymph nodes and tissues may be related to both nonneoplastic and neoplastic lymphoid proliferations and histiocytic and nonhematolymphoid processes. Understanding the differential diagnosis of reactive eosinophilia and the potential for overlapping clinical and pathologic findings is critical in reaching the correct diagnosis so that patients can be treated appropriately.

Gene Expression Comparison between Sézary Syndrome and Lymphocytic-Variant Hypereosinophilic Syndrome Refines Biomarkers for Sézary Syndrome.

Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma (CTCL) with poor prognosis, is characterized by the clinical hallmarks of circulating malignant T cells, erythroderma and lymphadenopathy. However, highly variable clinical skin manifestations and similarities with benign mimickers can lead to significant diagnostic delay and inappropriate therapy that can lead to disease progression and mortality. SS has been the focus of numerous transcriptomic-profiling studies to identify sensitive and specific diagnostic and prognostic biomarkers. Benign inflammatory disease controls (e.g., psoriasis, atopic dermatitis) have served to identify chronic inflammatory phenotypes in gene expression profiles, but provide limited insight into the lymphoproliferative and oncogenic roles of abnormal gene expression in SS. This perspective was recently clarified by a transcriptome meta-analysis comparing SS and lymphocytic-variant hypereosinophilic syndrome, a benign yet often clonal T-cell lymphoproliferation, with clinical features similar to SS. Here we review the rationale for selecting lymphocytic-variant hypereosinophilic syndrome (L-HES) as a disease control for SS, and discuss differentially expressed genes that may distinguish benign from malignant lymphoproliferative phenotypes, including additional context from prior gene expression studies to improve understanding of genes important in SS.

Eosinophilia Associated With CD3-CD4+ T Cells: Characterization and Outcome of a Single-Center Cohort of 26 Patients.

Background: Lymphocytic variant hypereosinophilic syndrome is characterized by marked over-production of eosinophilopoietic factor(s) by dysregulated T cells leading to eosinophil expansion. In most cases, these T cells are clonal and express a CD3−CD4+ phenotype. As this is a rare disorder, presenting manifestations, disease course, treatment responses, and outcome are not well-characterized.Materials and Methods: In this retrospective single-center observational study, we reviewed medical files of all patients with persistent hypereosinophilia seen between 1994 and 2019 in whom CD3−CD4+ T cells were detected. Data collection included clinical and biological findings at presentation, treatment responses, disease course, and serial CD3−CD4+ T cell counts.Results: Our cohort comprises 26 patients, including 2 with hypereosinophilia of undetermined significance. All 24 symptomatic patients had cutaneous lesions and/or angioedema, and fasciitis was present in several cases. The aberrant T cell subset represented 2% or less total lymphocytes in 11 subjects. TCR gene rearrangement patterns on whole blood were polyclonal in these cases, while they all had serum CCL17/TARC levels above 1,500 pg/ml. Disease manifestations were mild and did not require maintenance therapy in roughly one third of the cohort, while two thirds required long-term oral corticosteroids and/or second-line agents. Among these, interferon-alpha was the most effective treatment option with a response observed in 8/8 patients, one of whom was cured of disease. Treatment had to be interrupted in most cases however due to poor tolerance and/or development of secondary resistance. Anti-interleukin-5 antibodies reduced blood eosinophilia in 5/5 patients, but clinical responses were disappointing. A sub-group of 5 patients had severe treatment-refractory disease, and experienced significant disease- and treatment-related morbidity and mortality, including progression to T cell lymphoma in three.Conclusions: This retrospective longitudinal analysis of the largest monocentric cohort of CD3−CD4+ T cell associated lymphocytic variant hypereosinophilic syndrome published so far provides clinicians confronted with this rare disorder with relevant new data on patient presentation and outcome that should help tailor therapy and follow-up to different levels of disease severity. It highlights the need for novel therapeutic options, especially for the subset of patients with severe treatment-refractory disease. Future research efforts should be made toward understanding CD3−CD4+ T cell biology in order to develop new treatments that target primary pathogenic mechanisms.

Prevalence and spectrum of T-cell lymphoproliferative disorders in patients with Hypereosinophilia: A reference laboratory experience

Hypereosinophilia (HE) is defined as persistently elevated absolute eosinophil count (AEC) ≥ 1.5 × 109/L, which can be due to a variety of underlying causes. In this study, we investigated the prevalence and spectrum of T-cell lymphoproliferative disorders in 124 consecutive patients with HE by flow cytometric immunophenotyping. Available medical records, pathology reports and T-cell receptor (TCR) gene rearrangement were reviewed. Fifteen patients (12%) with HE had abnormal T-cell populations that were initially detected by flow cytometry. The presence of immunophenotypically abnormal T cells was not associated with higher AEC or higher absolute lymphocyte count levels, in comparison to those without abnormal T cells. Molecular studies concordantly identified a clonal TCR gene rearrangement in 8 of 10 cases tested. Based on the combination of clinical presentation, morphologic findings and laboratory studies, seven patients were diagnosed with the lymphocytic variant of hypereosinophilic syndrome and five with overt T-cell lymphoma (4 peripheral T-cell lymphoma NOS, 1 primary cutaneous T-cell lymphoma). The remaining three had an unknown diagnosis due to lack of information and additional workup would be warranted. These findings underscore the importance of flow cytometry as a screening tool to identify T-cell lymphoproliferative disorders in patients with HE.

Assessment of T-cell polarization on the basis of surface marker expression: Diagnosis and potential therapeutic implications in lymphocytic variant hypereosinophilic syndrome

Assessment of T-cell polarization on the basis of surface marker expression: Diagnosis and potential therapeutic implications in lymphocytic variant hypereosinophilic syndrome

Transcriptome analysis of Sézary syndrome and lymphocytic-variant hypereosinophilic syndrome T cells reveals common and divergent genes.

Sézary syndrome (SS) is an aggressive cutaneous T cell lymphoma with pruritic skin inflammation and immune dysfunction, driven by neoplastic, clonal memory T cells in both peripheral blood and skin. To gain insight into abnormal gene expression promoting T cell dysfunction, lymphoproliferation and transformation in SS, we first compared functional transcriptomic profiles of both resting and activated CD4+CD45RO+ T cells from SS patients and normal donors to identified differential expressed genes. Next, a meta-analysis was performed to compare our SS data to public microarray data from a novel benign disease control, lymphocytic-variant hypereosinophilic syndrome (L-HES). L-HES is a rare, clonal lymphoproliferation of abnormal memory T cells that produces similar clinical symptoms as SS, including severe pruritus and eosinophilia. Comparison revealed gene sets specific for either SS (370 genes) or L-HES (519 genes), and a subset of 163 genes that were dysregulated in both SS and L-HES T cells compared to normal donor T cells. Genes confirmed by RT-qPCR included elevated expression of PLS3, TWIST1 and TOX only in SS, while IL17RB mRNA was increased only in L-HES. CDCA7 was increased in both diseases. In an L-HES patient who progressed to peripheral T cell lymphoma, the malignant transformation identified increases in the expression of CDCA7, TIGIT, and TOX, which are highly expressed in SS, suggesting that these genes contribute to neoplastic transformation. In summary, we have identified gene expression biomarkers that implicate a common transformative mechanism and others that are unique to differentiate SS from L-HES.

Romidepsin is an effective and well-tolerated therapy in CD3−CD4+ lymphocyte-variant hypereosinophilic syndrome: A case report

Romidepsin is an effective and well-tolerated therapy in CD3−CD4+ lymphocyte-variant hypereosinophilic syndrome: A case report

1037 Transcriptome analysis in Sézary syndrome and lymphocytic variant hypereosinophilic syndrome identify common and unique genes

1037 Transcriptome analysis in Sézary syndrome and lymphocytic variant hypereosinophilic syndrome identify common and unique genes

014 - Analysis of Sézary syndrome (SS) and lymphocytic variant of hypereosinophilic syndrome (L-HES) transcriptome identify common genes to reflect similar manifestation and highlight genes important in proliferation

014 - Analysis of Sézary syndrome (SS) and lymphocytic variant of hypereosinophilic syndrome (L-HES) transcriptome identify common genes to reflect similar manifestation and highlight genes important in proliferation

AN EVOLVING DIAGNOSIS OF A DIFFUSE ERYTHRODERMIC RASH

Introduction Lymphocytic variant hypereosinophilic syndrome (L-HES) is a rare condition that can be challenging to diagnose. In patients presenting with an erythrodermic skin rash and eosinophilia, it is imperative to review the L-HES diagnostic criteria and periodically reassess for alternative etiologies, particularly with disease progression. Case Description A 39-year-old female presented with a 4-year history of an erythematous, confluent plaque-like rash. Initially, her skin biopsy demonstrated granulomatous dermatitis with necrobiosis but no eosinophils. She had a peripheral absolute eosinophil count of 1100/uL. Her bone marrow biopsy demonstrated a CD4+, CD3-T-cell population with small, non-necrotizing granulomas and no clonal eosinophilia. She was diagnosed with L-HES and started on high-dose glucocorticoids with initial skin improvement; however, skin symptoms subsequently progressed, covering 90% of her body surface area. She was then managed as cutaneous sarcoidosis, but treatment with methotrexate and leflunomide did not improve symptoms. Given her persistent symptoms, she underwent repeat skin biopsy, which demonstrated cutaneous T-cell lymphoma. Symptoms improved with romidepsin. Discussion This patient had initial findings suggestive of L-HES but did not meet L-HES diagnostic criteria. She never had an absolute eosinophil count >1500/uL, nor tissue biopsy demonstrating eosinophil-mediated organ damage. Her disease progression led to re-evaluation and a malignancy diagnosis. Although patients with L-HES can progress to cutaneous T-cell lymphoma, clonal CD4+, CD3- T cells can be found in primary cutaneous T-cell lymphoma without prior HES diagnosis. This case illustrates the importance of continued diagnostic inquiry when the diagnosis is unclear and symptoms progress despite therapy. Lymphocytic variant hypereosinophilic syndrome (L-HES) is a rare condition that can be challenging to diagnose. In patients presenting with an erythrodermic skin rash and eosinophilia, it is imperative to review the L-HES diagnostic criteria and periodically reassess for alternative etiologies, particularly with disease progression. A 39-year-old female presented with a 4-year history of an erythematous, confluent plaque-like rash. Initially, her skin biopsy demonstrated granulomatous dermatitis with necrobiosis but no eosinophils. She had a peripheral absolute eosinophil count of 1100/uL. Her bone marrow biopsy demonstrated a CD4+, CD3-T-cell population with small, non-necrotizing granulomas and no clonal eosinophilia. She was diagnosed with L-HES and started on high-dose glucocorticoids with initial skin improvement; however, skin symptoms subsequently progressed, covering 90% of her body surface area. She was then managed as cutaneous sarcoidosis, but treatment with methotrexate and leflunomide did not improve symptoms. Given her persistent symptoms, she underwent repeat skin biopsy, which demonstrated cutaneous T-cell lymphoma. Symptoms improved with romidepsin. This patient had initial findings suggestive of L-HES but did not meet L-HES diagnostic criteria. She never had an absolute eosinophil count >1500/uL, nor tissue biopsy demonstrating eosinophil-mediated organ damage. Her disease progression led to re-evaluation and a malignancy diagnosis. Although patients with L-HES can progress to cutaneous T-cell lymphoma, clonal CD4+, CD3- T cells can be found in primary cutaneous T-cell lymphoma without prior HES diagnosis. This case illustrates the importance of continued diagnostic inquiry when the diagnosis is unclear and symptoms progress despite therapy.