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Nature Reviews. Rheumatology Sep 2017First described in the early 1980s, antiphospholipid syndrome (APS) is a unique form of acquired autoimmune thrombophilia in which patients present with clinical... (Review)
Review
First described in the early 1980s, antiphospholipid syndrome (APS) is a unique form of acquired autoimmune thrombophilia in which patients present with clinical features of recurrent thrombosis and pregnancy morbidity and persistently test positive for the presence of antiphospholipid antibodies (aPL). At least one clinical (vascular thrombosis or pregnancy morbidity) and one lab-based (positive test result for lupus anticoagulant, anticardiolipin antibodies and/or anti-β2-glycoprotein 1 antibodies) criterion have to be met for a patient to be classified as having APS. However, the clinical spectrum of APS encompasses additional manifestations that can affect many organs and cannot be explained exclusively by patients being in a prothrombotic state; clinical manifestations not listed in the classification criteria (known as extra-criteria manifestations) include neurologic manifestations (chorea, myelitis and migraine), haematologic manifestations (thrombocytopenia and haemolytic anaemia), livedo reticularis, nephropathy and valvular heart disease. Increasingly, research interest has focused on the development of novel assays that might be more specific for APS than the current aPL tests. This Review focuses on the current classification criteria for APS, presenting the role of extra-criteria manifestations and lab-based tests. Diagnostic approaches to difficult cases, including so-called seronegative APS, are also discussed.
Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Diagnostic Tests, Routine; Female; Humans; Male; Needs Assessment; Sensitivity and Specificity; Severity of Illness Index
PubMed: 28769114
DOI: 10.1038/nrrheum.2017.124 -
Journal of Clinical Immunology Jul 2018Deficiency of ADA2 (DADA2) is the first molecularly described monogenic vasculitis syndrome. DADA2 is caused by biallelic hypomorphic mutations in the ADA2 gene that... (Review)
Review
Deficiency of ADA2 (DADA2) is the first molecularly described monogenic vasculitis syndrome. DADA2 is caused by biallelic hypomorphic mutations in the ADA2 gene that encodes the adenosine deaminase 2 (ADA2) protein. Over 60 disease-associated mutations have been identified in all domains of ADA2 affecting the catalytic activity, protein dimerization, and secretion. Vasculopathy ranging from livedo reticularis to polyarteritis nodosa (PAN) and life-threatening ischemic and/or hemorrhagic stroke dominate the clinical features of DADA2. Vasculitis and inflammation can affect many organs, explaining the intestinal, hepatological, and renal manifestations. DADA2 should be primarily considered in patients with early-onset fevers, rashes, and strokes even in the absence of positive family history. Hematological manifestations include most commonly hypogammaglobulinemia, although pure red cell aplasia (PRCA), immune thrombocytopenia, and neutropenia have been increasingly reported. Thus, DADA2 may unify a variety of syndromes previously not thought to be related. The first-line treatment consists of TNF-inhibitors and is effective in controlling inflammation and in preserving vascular integrity. Hematopoietic stem cell transplantation (HSCT) has been successful in a group of patients presenting with hematological manifestations. ADA2 is highly expressed in myeloid cells and plays a role in the differentiation of macrophages; however, its function is still largely undetermined. Deficiency of ADA2 has been linked to an imbalance in differentiation of monocytes towards proinflammatory M1 macrophages. Future research on the function of ADA2 and on the pathophysiology of DADA2 will improve our understanding of the condition and promote early diagnosis and targeted treatment.
Topics: Adenosine Deaminase; Animals; Combined Modality Therapy; Disease Management; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Intercellular Signaling Peptides and Proteins; Mutation; Phenotype; Quantitative Trait Loci; Treatment Outcome; Vasculitis
PubMed: 29951947
DOI: 10.1007/s10875-018-0525-8 -
Dermatology (Basel, Switzerland) 2021Coronavirus disease-19 (COVID-19) is an ongoing global pandemic caused by the "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), which was isolated for the... (Review)
Review
BACKGROUND
Coronavirus disease-19 (COVID-19) is an ongoing global pandemic caused by the "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), which was isolated for the first time in Wuhan (China) in December 2019. Common symptoms include fever, cough, fatigue, dyspnea and hypogeusia/hyposmia. Among extrapulmonary signs associated with COVID-19, dermatological manifestations have been increasingly reported in the last few months.
SUMMARY
The polymorphic nature of COVID-19-associated cutaneous manifestations led our group to propose a classification, which distinguishes the following six main clinical patterns: (i) urticarial rash, (ii) confluent erythematous/maculopapular/morbilliform rash, (iii) papulovesicular exanthem, (iv) chilblain-like acral pattern, (v) livedo reticularis/racemosa-like pattern, (vi) purpuric "vasculitic" pattern. This review summarizes the current knowledge on COVID-19-associated cutaneous manifestations, focusing on clinical features and therapeutic management of each category and attempting to give an overview of the hypothesized pathophysiological mechanisms of these conditions.
Topics: Acrodermatitis; COVID-19; Exanthema; Humans; Livedo Reticularis; Patient Acuity; Purpura; SARS-CoV-2; Urticaria
PubMed: 33232965
DOI: 10.1159/000512932 -
JAMA Dermatology Nov 2021VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described severe adult-onset autoinflammatory disease that is associated with myeloid...
IMPORTANCE
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described severe adult-onset autoinflammatory disease that is associated with myeloid lineage-restricted ubiquitin-activating enzyme 1 (UBA1) somatic variations that primarily affect the skin (Sweet syndrome), cartilage, and bone marrow. Skin symptoms have been poorly described.
OBJECTIVE
To better describe clinical and pathological skin manifestations and their pathophysiology in VEXAS syndrome.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter retrospective case series study of clinical and histological features of 8 patients with VEXAS syndrome and skin involvement was conducted in France from December 2007 to March 2021, with molecular data obtained from March to April 2022. Any UBA1 variations were detected by Sanger or next-generation sequencing that was performed on bone marrow and formalin-fixed paraffin-embedded tissue sections of skin lesion biopsies.
RESULTS
All 8 patients were men, and the median age at symptom onset was 65.5 years (interquartile range, 54-76 years). All patients had neutrophilic dermatosis skin lesions, including tender red or violaceous papules, sometimes edematous, without fever, arthralgia, recurrence or pathergy, inflammatory edematous papules on the neck and trunk (sometimes umbilicated), and firm erythematous purpuric or pigmented infiltrated plaques and nodules. Three patients had livedo racemosa. The infiltrates were perivascular and consisted of mature neutrophils with leukocytoclasia, which were admixed with myeloperoxidase-positive CD163-positive myeloid cells with indented nuclei and lymphoid cells in all cases. A sequencing analysis of paired bone marrow samples and skin lesion biopsies identified the same loss-of-function UBA1 variation in both samples for all patients.
CONCLUSIONS AND RELEVANCE
This case series study describes the different clinical presentations of skin lesions found in VEXAS syndrome, which is characterized histologically by neutrophilic dermatosis. The findings suggested that the dermal infiltrates seen in VEXAS skin lesions are derived from the pathological myeloid clone. This suggests that using therapies that target the pathological clone may be effective in the long-term management of the disease.
Topics: Adult; Bone Marrow; Humans; Male; Mutation; Retrospective Studies; Sweet Syndrome; Ubiquitin-Activating Enzymes
PubMed: 34495287
DOI: 10.1001/jamadermatol.2021.3344 -
Arthritis and Rheumatism Apr 2002To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression.
OBJECTIVE
To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression.
METHODS
The clinical and serologic features of APS (Sapporo preliminary criteria) in 1,000 patients from 13 European countries were analyzed using a computerized database.
RESULTS
The cohort consisted of 820 female patients (82.0%) and 180 male patients (18.0%) with a mean +/- SD age of 42 +/- 14 years at study entry. "Primary" APS was present in 53.1% of the patients; APS was associated with systemic lupus erythematosus (SLE) in 36.2%, with lupus-like syndrome in 5.0%, and with other diseases in 5.9%. A variety of thrombotic manifestations affecting the majority of organs were recorded. A catastrophic APS occurred in 0.8% of the patients. Patients with APS associated with SLE had more episodes of arthritis and livedo reticularis, and more frequently exhibited thrombocytopenia and leukopenia. Female patients had a higher frequency of arthritis, livedo reticularis, and migraine. Male patients had a higher frequency of myocardial infarction, epilepsy, and arterial thrombosis in the lower legs and feet. In 28 patients (2.8%), disease onset occurred before age 15; these patients had more episodes of chorea and jugular vein thrombosis than the remaining patients. In 127 patients (12.7%), disease onset occurred after age 50; most of these patients were men. These patients had a higher frequency of stroke and angina pectoris, but a lower frequency of livedo reticularis, than the remaining patients.
CONCLUSION
APS may affect any organ of the body and display a broad spectrum of manifestations. An association with SLE, the patient's sex, and the patient's age at disease onset can modify the disease expression and define specific subsets of APS.
Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Antiphospholipid Syndrome; Autoantibodies; Child; Child, Preschool; Cohort Studies; Diagnosis, Differential; Female; Humans; Infant; Infant, Newborn; Lupus Vasculitis, Central Nervous System; Male; Middle Aged; Prevalence; Sex Distribution
PubMed: 11953980
DOI: 10.1002/art.10187 -
International Journal of Women's... Sep 2020Coronaviridae (CoV) is a large family of zoonotic viruses linked to a range of diseases from the common cold to severe acute and Middle East respiratory syndrome CoV... (Review)
Review
Coronaviridae (CoV) is a large family of zoonotic viruses linked to a range of diseases from the common cold to severe acute and Middle East respiratory syndrome CoV epidemics. In 2019, a novel virus emerged from Wuhan, China, and resulted in a marked worldwide outbreak of respiratory illness. Prevention and containment became the prioritized intervention against COVID-19, coupled with a continued search for hallmarks of the disease that would allow early detection and provide insight into management and triage. Cutaneous findings associated with COVID-19 include diffuse maculopapular rashes, livedo reticularis, and acro-ischemic "COVID toes." These skin findings occurred anywhere from days before respiratory symptom onset to weeks after recovery, and predominantly in child and adolescent populations. The role of dermatologists can be expanded during this COVID-19 pandemic to help identify disease through cutaneous presentations.
PubMed: 32838013
DOI: 10.1016/j.ijwd.2020.06.006 -
Medicina 2017Calciphylaxis is vasculopathy characterized by ischemia and painful skin necrosis due to calcification and intimal fibroplasia of thrombosis of the panicular arterioles....
Calciphylaxis is vasculopathy characterized by ischemia and painful skin necrosis due to calcification and intimal fibroplasia of thrombosis of the panicular arterioles. It most frequently compromises patients with terminal chronic renal failure and has a high mortality rate. Biopsy of skin lesions is used as a diagnostic method. No specific laboratory findings have been recorded. Skin lesions usually begin in the extremities like a painful purplish mottling similar to "livedo reticularis". The natural evolution is to ulcers and bedsores. The first line of treatment involves the care of skin lesions and antibiotic therapy. Sodium thiosulfate is used as treatment due to its antioxidant activity and as a chelating. Two clinical cases are here reported.
Topics: Adult; Calciphylaxis; Combined Modality Therapy; Debridement; Female; Humans; Kidney Failure, Chronic; Middle Aged
PubMed: 28825580
DOI: No ID Found -
The Israel Medical Association Journal... Feb 2015Livedo reticularis is a common cutaneous manifestation of APS and may be a prognostic marker of more severe disease. It is associated with arterial and venous thrombosis... (Review)
Review
Livedo reticularis is a common cutaneous manifestation of APS and may be a prognostic marker of more severe disease. It is associated with arterial and venous thrombosis and pregnancy morbidity irrespective of the presence of antiphospholipid antibodies. Recent results suggest the possibility of an association with accelerated atherosclerosis in patients with livedo. Given the similarities between APS and livedo (aPL negative), experts in this field believe that livedo may represent the so-called seronegative antiphospholipid syndrome, although the exact relationship of livedo with seronegative APS remains to be elucidated. LV may present as painful cutaneous ulcers that are often difficult to treat. The underlying pathology involves prothrombotic as well as immunological processes with some overlap with APS. Treatment remains challenging and results are often variable.
Topics: Adult; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Atherosclerosis; Diagnosis, Differential; Disease Management; Female; Humans; Livedo Reticularis; Pregnancy; Pregnancy Complications; Prognosis; Thrombosis
PubMed: 26223086
DOI: No ID Found -
The American Journal of Emergency... Sep 2020The novel coronavirus disease of 2019 (COVID-19) is associated with significant morbidity and mortality. While much of the focus has been on the cardiac and pulmonary... (Review)
Review
UNLABELLED
The novel coronavirus disease of 2019 (COVID-19) is associated with significant morbidity and mortality. While much of the focus has been on the cardiac and pulmonary complications, there are several important dermatologic components that clinicians must be aware of.
OBJECTIVE
This brief report summarizes the dermatologic manifestations and complications associated with COVID-19 with an emphasis on Emergency Medicine clinicians.
DISCUSSION
Dermatologic manifestations of COVID-19 are increasingly recognized within the literature. The primary etiologies include vasculitis versus direct viral involvement. There are several types of skin findings described in association with COVID-19. These include maculopapular rashes, urticaria, vesicles, petechiae, purpura, chilblains, livedo racemosa, and distal limb ischemia. While most of these dermatologic findings are self-resolving, they can help increase one's suspicion for COVID-19.
CONCLUSION
It is important to be aware of the dermatologic manifestations and complications of COVID-19. Knowledge of the components is important to help identify potential COVID-19 patients and properly treat complications.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Global Health; Humans; Incidence; Pandemics; Pneumonia, Viral; SARS-CoV-2; Skin; Skin Diseases
PubMed: 32731141
DOI: 10.1016/j.ajem.2020.06.011