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

Abstract

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.

Localized pemphigus exacerbation associated with underlying breast cancer

“…PNP was ruled out due to i) the absence of severe mucosal involvement and internal complications at the time of pemphigus relapse, ii) negative results of the indirect immunofluorescence test using rat bladder as a substrate, and iii) lack of evidence of interface dermatitis in the skin biopsy. 8 Although the breast cancer was likely present before the onset of the first pemphigus manifestation, the causal relationship between the presence of the tumor and the localized pemphigus flare was strengthened by the prompt disease improvement following the surgical removal of the tumor and the lack of recurrence of the pemphigus lesions on the postoperative skin.…”

Dupilumab for the treatment of recalcitrant eosinophilic dermatosis of haematologic malignancy

“…1 Notwithstanding the effectiveness of systemic glucocorticoids and other immunosuppressants as frontline therapies, relapses are commonly observed upon discontinuation. 2 A woman in her 50s presented to our outpatient dermatology clinic for a 2-month history of a persistent pruritic rash distributed over her upper and lower limbs. She was suffering from a small lymphocytic lymphoma, for which she had received six cycles of rituximab combined with bendamustine, ended 3 months before the onset of the skin rash, achieving a complete remission.…”

“…The management of patients with EDHM can prove challenging, due to the recurrent behaviour of the dermatosis, the association with persistent and invalidating pruritus, and the risks underlying prolonged immunosuppressive therapies in these patients. 2 On a pathogenetic basis, a shift in Th2-type immunity, induced by the tumour itself or the associated therapies, has been hypothesized as an explanation for EDHM. 3 However, the expression of Th2-associated molecules in patients with EDHM has not been analysed so far.…”

“…Given the lack of immunosuppressive activity, dupilumab may represent a safer option than glucocorticoids and immunosuppressants, in terms of risk of infections and leukaemia progression. 2 Remarkably, dupilumab has been shown to induce disease progression in some cases of cutaneous T-cell lymphoma (CTCL), 8 although in others it has been used successfully without safety issues for long-term management of CTCL-associated pruritus. 9 Close monitoring haematologic patients receiving IL-4 targeting drugs is thereby of utmost importance.…”

Retrospective analysis of 578 inpatient dermatology consultations in hematology and hematopoietic stem cell transplant patients

“…Previous studies have confirmed our finding that neutrophilic dermatoses are most frequently associated with myeloid malignancy, and emerging evidence suggests the skin-infiltrating neutrophils may be clonally related to the neoplastic cells. 14 Patients with lymphoid malignancies had more frequent viral infection with cutaneous manifestations; however, whether this is due to the malignancy itself or other factors remains unknown. Lastly, although we did not collect data regarding pharmacotherapy, we suspect that the higher frequency of drug reactions in severely neutropenic patients is secondary to the additional antimicrobial and anticancer therapies these patients receive.…”