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      Morphologic Spectrum of Lymphadenopathy in Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome

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      Archives of Pathology & Laboratory Medicine
      Archives of Pathology and Laboratory Medicine

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          Abstract

          Context.—

          Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS) is a drug-induced, adverse T-cell–mediated hypersensitivity reaction that most often involves skin. The pathologic findings of DRESS-related lymphadenopathy have been described infrequently in the literature.

          Objective.—

          To present a case series of DRESS-related lymphadenopathy with an emphasis on the morphologic spectrum.

          Design.—

          We describe detailed clinical and pathologic findings along with the literature review. We focus on the differential diagnosis between DRESS lymphadenopathy and angioimmunoblastic T-cell lymphoma (AITL).

          Results.—

          There were 4 men and 1 woman with a mean age of 41 years (range, 23–59 years). One patient (20%) died. Three lymph node biopsy specimens showed a pattern reminiscent of AITL (AITL-like pattern) and 2 cases showed necrotizing lymphadenitis (Kikuchi-like pattern), associated with vasculitis in 1 case. The AITL-like morphology of DRESS-related lymphadenopathy may be difficult to distinguish from genuine AITL. The clinical information is important for differential diagnosis, including history of drug exposure, age, and the rarity or absence of AITL-associated manifestations such as hemolytic anemia and hypergammaglobulinemia. Molecular analysis of the T-cell receptor genes is helpful, typically revealing a polyclonal pattern in DRESS-related lymphadenopathy.

          Conclusions.—

          In the literature, 4 histologic patterns of DRESS lymphadenopathy have been described: reactive lymphoid hyperplasia, necrotizing lymphadenitis, Hodgkin lymphoma–like, and AITL-like. These patterns, particularly those that resemble lymphoma, highlight the importance of correct diagnosis to avoid unnecessary therapies.

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          Most cited references37

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          How regulatory T cells work.

          Regulatory T (T(Reg)) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. However, they also limit beneficial responses by suppressing sterilizing immunity and limiting antitumour immunity. Given that T(Reg) cells can have both beneficial and deleterious effects, there is considerable interest in determining their mechanisms of action. In this Review, we describe the basic mechanisms used by T(Reg) cells to mediate suppression and discuss whether one or many of these mechanisms are likely to be crucial for T(Reg)-cell function. In addition, we propose the hypothesis that effector T cells may not be 'innocent' parties in this suppressive process and might in fact potentiate T(Reg)-cell function.
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            Regulatory T cells: how do they suppress immune responses?

            Regulatory T cells (Tregs), either natural or induced, suppress a variety of physiological and pathological immune responses. One of the key issues for understanding Treg function is to determine how they suppress other lymphocytes at the molecular level in vivo and in vitro. Here we propose that there may be a key suppressive mechanism that is shared by every forkhead box p3 (Foxp3)(+) Treg in vivo and in vitro in mice and humans. When this central mechanism is abrogated, it causes a breach in self-tolerance and immune homeostasis. Other suppressive mechanisms may synergistically operate with this common mechanism depending on the environment and the type of an immune response. Further, Treg-mediated suppression is a multi-step process and impairment or augmentation of each step can alter the ultimate effectiveness of Treg-mediated suppression. These findings will help to design effective ways for controlling immune responses by targeting Treg suppressive functions.
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              Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS).

              Since the first description by Saltzstein in 1959, the denomination of drug-induced pseudolymphoma was used to describe two cutaneous adverse drug reactions with a histological picture mimicking malignant lymphoma. On the basis of clinical presentation, this term includes two different patterns: (1) hypersensitivity syndrome which begins acutely in the first 2 months after the initiation of the drug and associates fever, a severe skin disease with characteristic infiltrated papules and facial edema or an exfoliative dermatitis, lymphadenopathy, hematologic abnormalities (hypereosinophilia, atypical lymphocytes) and organ involvement such as hepatitis, carditis, interstitial nephritis, or interstitial pneumonitis. The cutaneous histological pattern shows a lymphocytic infiltrate, sometimes mimicking a cutaneous lymphoma, and the mortality rate is about 10%. When organ involvement exists, corticosteroids are often prescribed with dramatic improvement. Relapses may occur. (2) drug-induced pseudolymphoma which has a more insidious beginning with nodules and infiltrated plaques appearing several weeks after the beginning of the drug without constitutional symptoms. A pseudolymphoma pattern is seen on cutaneous histological slides. Complete improvement is usual after drug withdrawal, but a delayed lymphoma is possible. To decrease the ambiguity of the denomination of hypersensitivity syndrome, we propose the term of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms).
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                Author and article information

                Journal
                Archives of Pathology & Laboratory Medicine
                Archives of Pathology and Laboratory Medicine
                1543-2165
                0003-9985
                September 01 2022
                December 13 2021
                September 01 2022
                December 13 2021
                : 146
                : 9
                : 1084-1093
                Article
                10.5858/arpa.2021-0087-OA
                fe1faefd-9c9b-471e-915b-e9dcbfe739a5
                © 2021
                History

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