Bullous eruption in a patient with B‐cell chronic lymphocytic leukemia: a diagnostic challenge

Maglie, Roberto; Antiga, Emiliano; Vannucchi, Margherita; Bianco, Elena Del; Bianchi, Beatrice; Massi, Daniela; Caproni, Marzia

doi:10.1111/ijd.13807

Cited by 13 publications

(11 citation statements)

References 10 publications

(12 reference statements)

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“…Patients in complete clinical response also display increased number of IL-10-producing regulatory B-cells and absence of Dsg3-IgG + B-cells (136). Altogether, these findings suggest that RTX induces a complete reset of the B-cell repertoire in pemphigus, favoring early appearance of immature B-cells and anti-inflammatory regulatory B (Breg) cells, and delayed reappearance of Dsg-specific memory B-cells, which eventually account for disease relapse (136, 139).…”

Section: Treatmentmentioning

confidence: 93%

Pemphigus: Current and Future Therapeutic Strategies

et al. 2019

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Pemphigus encompasses a heterogeneous group of autoimmune blistering diseases, which affect both mucous membranes and the skin. The disease usually runs a chronic-relapsing course, with a potentially devastating impact on the patients' quality of life. Pemphigus pathogenesis is related to IgG autoantibodies targeting various adhesion molecules in the epidermis, including desmoglein (Dsg) 1 and 3, major components of desmosomes. The pathogenic relevance of such autoantibodies has been largely demonstrated experimentally. IgG autoantibody binding to Dsg results in loss of epidermal keratinocyte adhesion, a phenomenon referred to as acantholysis. This in turn causes intra-epidermal blistering and the clinical appearance of flaccid blisters and erosions at involved sites. Since the advent of glucocorticoids, the overall prognosis of pemphigus has largely improved. However, mortality persists elevated, since long-term use of high dose corticosteroids and adjuvant steroid-sparing immunosuppressants portend a high risk of serious adverse events, especially infections. Recently, rituximab, a chimeric anti CD20 monoclonal antibody which induces B-cell depletion, has been shown to improve patients' survival, as early rituximab use results in higher disease remission rates, long term clinical response and faster prednisone tapering compared to conventional immunosuppressive therapies, leading to its approval as a first line therapy in pemphigus. Other anti B-cell therapies targeting B-cell receptor or downstream molecules are currently tried in clinical studies. More intriguingly, a preliminary study in a preclinical mouse model of pemphigus has shown promise regarding future therapeutic application of Chimeric Autoantibody Receptor T-cells engineered using Dsg domains to selectively target autoreactive B-cells. Conversely, previous studies from our group have demonstrated that B-cell depletion in pemphigus resulted in secondary impairment of T-cell function; this may account for the observed long-term remission following B-cell recovery in rituximab treated patients. Likewise, our data support the critical role of Dsg-specific T-cell clones in orchestrating the inflammatory response and B-cell activation in pemphigus. Monitoring autoreactive T-cells in patients may indeed provide further information on the role of these cells, and would be the starting point for designating therapies aimed at restoring the lost immune tolerance against Dsg. The present review focuses on current advances, unmet challenges and future perspectives of pemphigus management.

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Section: Treatmentmentioning

confidence: 93%

Pemphigus: Current and Future Therapeutic Strategies

et al. 2019

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“…Additional histopathologic features include dermal oedema, dermal-epidermal detachment, eosinophilic spongiosis and parakeratosis [ 113 ]. In patients presenting with blisters and histological evidence of dermal-epidermal detachment, direct immunofluorescence of perilesional skin or serum tests usually fail to identify autoantibodies against BP180 or other proteins of the dermal–epidermal junction [ 114 ]. This means EDHM can be distinguished from BP or other subepidermal autoimmune bullous disorders.…”

Section: Eosinophilic Dermatoses and Related Skin Manifestationsmentioning

confidence: 99%

Immune-Mediated Dermatoses in Patients with Haematological Malignancies: A Comprehensive Review

et al. 2020

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Haematological malignancies induce important alterations of the immune system, which account for the high frequency of autoimmune complications observed in patients. Cutaneous immune-mediated diseases associated with haematological malignancies encompass a heterogeneous group of dermatoses, including, among others, neutrophilic and eosinophilic dermatoses, autoantibody-mediated skin diseases, vasculitis and granulomatous dermatoses. Some of these diseases, such as paraneoplastic pemphigus, are associated with an increased risk of death; others, such as eosinophilic dermatoses of haematological malignancies, run a benign clinical course but portend a significant negative impairment on a patient's quality of life. In rare cases, the skin eruption reflects immunological alterations associated with an unfavourable prognosis of the associated haematological disorder. Therapeutic management of immune-mediated skin diseases in patients with haematological malignancies is often challenging. Systemic corticosteroids and immunosuppressive drugs are considered frontline therapies but may considerably augment the risk of serious infections. Indeed, developing a specific targeted therapeutic approach is of crucial importance for this particularly fragile patient population. This review provides an up-to-date overview on the immune-mediated skin diseases most frequently encountered by patients with onco-haematological disorders, discussing new pathogenic advances and therapeutic options on the horizon.

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“…2,3,4 Histopathologically, dermo-epidermal detachment and eosinophil-rich dermal inflammatory infiltrates are classically detected in both diseases. 4 Finally, EDHM may show confounding immunopathologic features, as reported in a study by Bottoni et al, in which six B-CLL patients with insect bite-like reactions had positive anti-BP180 antibodies on immunoblotting test, 5 and in a case by our group, in which a B-CLL patient with EDHM had linear deposition of Immunoglobulin M and C3 at direct immunofluorescence test. 4 Indeed, EDHM and BP appear challenging to distinguish, leading to potential diagnostic pitfalls.…”

Section: Accepted Manuscriptmentioning

confidence: 99%