The Growing Spectrum of DADA2 Manifestations—Diagnostic and Therapeutic Challenges Revisited

Escherich, Carolin S; Bötticher, Benedikt; Harmsen, Stefani; Hömberg, M.; Schaper, Jörg; Lorenz, Myriam Ricarda; Schwarz, Klaus; Oommen, Prasad T.

doi:10.3389/fped.2022.885893

Cited by 6 publications

(8 citation statements)

References 30 publications

(96 reference statements)

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“…Low‐density granulocytes have also been detected in a monogenic condition named deficiency of adenosine deaminase 2 (DADA2) where the gene ( ADA2 ) that encodes an enzyme involved in the metabolism of adenosine is affected 91 . These patients present with recurrent episodes of fever, early onset lacunar strokes and cutaneous involvement, as well as features of the systemic vasculitis polyarteritis nodosa 91‐93 . The condition tends to respond to TNF blockade 93 .…”

Section: Ldgs In Other Inflammatory/autoimmune Conditionsmentioning

confidence: 99%

“…91 These patients present with recurrent episodes of fever, early onset lacunar strokes and cutaneous involvement, as well as features of the systemic vasculitis polyarteritis nodosa. [91][92][93] The condition tends to respond to TNF blockade. 93 LDGs have been detected in DADA2 patients; they are mainly CD10 + and display enhanced NET formation that activates macrophages to release TNFα.…”

Section: Deficiency Of Adenosine Deaminasementioning

confidence: 99%

“…[91][92][93] The condition tends to respond to TNF blockade. 93 LDGs have been detected in DADA2 patients; they are mainly CD10 + and display enhanced NET formation that activates macrophages to release TNFα. 94 Indeed, those patients with DADA2 that were treated with anti-TNF agents displayed lower numbers of LDGs than those with active disease.…”

Section: Deficiency Of Adenosine Deaminasementioning

confidence: 99%

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Low‐density granulocytes in systemic autoimmunity and autoinflammation

Carmona-Rivera

Kaplan

2022

Immunological Reviews

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Born in the bone marrow, neutrophils are sentinel effector cells of the innate immune system that protect the host from microbes and other danger signals. Over a billion neutrophils are produced daily in the bone marrow, making these cells the most abundant white blood cells in circulation in humans. 1 Classically, neutrophils are considered short-lived cells and are the first to arrive to the site of infection to protect the host from pathogens. [2][3][4] These cells are endowed with a powerful arsenal of enzymes and antimicrobial peptides that are deployed to kill pathogens through different mechanisms that encompass phagocytosis, degranulation, and the formation of neutrophil extracellular traps (NETs). 3,5 With technological advances and the development of multi-omics approaches for data analysis, there have been significant advances in the understanding of neutrophils' phenotype and function in health and disease. [6][7][8] These cells can respond rapidly to immunological insults, return to the circulation and to the bone marrow after being in tissues (reverse transmigration),

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Section: Ldgs In Other Inflammatory/autoimmune Conditionsmentioning

confidence: 99%

Section: Deficiency Of Adenosine Deaminasementioning

confidence: 99%

Section: Deficiency Of Adenosine Deaminasementioning

confidence: 99%

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Low‐density granulocytes in systemic autoimmunity and autoinflammation

Carmona-Rivera

Kaplan

2022

Immunological Reviews

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“…It was first described in 2014 as an autoinflammatory disease 1 2. Since then, over 300 cases of DADA2 with varying clinical spectrum have been described 3. The DADA2 phenotypic spectrum resembles polyarteritis nodosa (PAN), ischaemic stroke and bone marrow failure (BMF).…”

Section: Introductionmentioning

confidence: 99%

Deficiency of adenosine deaminase 2: a genetic autoinflammatory disorder mimicking childhood polyarteritis nodosa

Mhatre,

Muranjan,

Karande

et al. 2024

BMJ Case Rep

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A girl in the early adolescent age group presented with multisystem manifestations in the form of periodic fever, recurrent abdominal pain, hypertension, seizure, skin lesions over the chest and gangrene over the left ring and middle fingertips. Her condition had remained undiagnosed for 11 years. On evaluation, she had features of polyarteritis nodosa (PAN) (multiple aneurysms, symmetric sensorimotor peripheral neuropathy, superficial ulcers, digital necrosis, myalgia, hypertension and proteinuria). As childhood PAN is a phenocopy of adenosine deaminase 2 with a different management strategy, whole-exome sequencing was performed, which revealed a pathogenic variant inADA2gene. The child was treated with TNF alpha inhibitors and showed improvement in the Paediatric Vasculitis Activity Score. The paper highlights the gratifying consequences of correct diagnosis with disease-specific therapy that ended the diagnostic odyssey, providing relief to the patient from debilitating symptoms and to the family from the financial burden of continued out-of-pocket health expenditure.

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“…Initially reported as a case series of 34 patients by two different groups, more than 300 cases have been reported worldwide [ 1 , 2 , 14 ]. However, DADA2 remains an underdiagnosed condition due to its strong phenotypic variability (fever, myalgia, rash, early onset of strokes, and hematological, neurological, and intestinal manifestations) which generates a difficult question about knowing the perfect time to raise a clinical suspicion [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

A Rare Genetic Mutation Leading to a Deficiency of Adenosine Deaminase 2 Enzyme in a Long-Standing Case of Cutaneous Polyarteritis Nodosa: A Case Report

Contractor¹,

Bhavsar²,

Joshi³

et al. 2022

Cureus

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Vasculitis is an inflammatory disorder of blood vessels affecting multiple organs. A deficiency of adenosine deaminase enzyme type 2 (DADA2) is a novel condition identified as a monogenic cause of cutaneous vasculitis. Since its first description in 2014, numerous case series and literature across several countries have expanded the scope of our understanding of this rare genetic condition. However, due to a scarcity of reported cases in adults, little is known regarding its full spectrum of clinical presentations, treatment guidelines, or outcomes in the adult patient population. It is established that it commonly affects multiple organ systems, such as the skin, musculoskeletal, neurological, hematological, gastrointestinal, and renal systems. It presents with a wide range of clinical manifestations, including fever, Livedoid rash, cutaneous polyarteritis nodosa, polyneuropathy, and immunodeficiency. Such a varied clinical spectrum opens an opportunity for discussion to list some of the differential signs of DADA2. In this article, we report a unique case of a 26-year-old male with a delay of nine years in diagnosing a genetic mutation that led to DADA2. In addition, a 10-year history of recurring cutaneous ulcers and peripheral neuropathy makes this case a noteworthy addition to the literature on cutaneous vasculitis and its miscellaneous causes.

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The Growing Spectrum of DADA2 Manifestations—Diagnostic and Therapeutic Challenges Revisited

Cited by 6 publications

References 30 publications

Low‐density granulocytes in systemic autoimmunity and autoinflammation

Low‐density granulocytes in systemic autoimmunity and autoinflammation

Deficiency of adenosine deaminase 2: a genetic autoinflammatory disorder mimicking childhood polyarteritis nodosa

A Rare Genetic Mutation Leading to a Deficiency of Adenosine Deaminase 2 Enzyme in a Long-Standing Case of Cutaneous Polyarteritis Nodosa: A Case Report

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