Background
The mucocutaneous clinical profile of patients with amyloidosis in Latin America has been scarcely reported.
Objective
To describe clinical characteristics of skin and mucosal ...manifestations in systemic amyloidosis in a tertiary care center in Mexico City.
Methods
A cross sectional, retrospective analytical study was performed in patients with systemic amyloidosis over a 15‐year period. Statistical analysis was done.
Results
A total of 98 patients were included (53 54% men; overall median age = 49 years old). Acquired systemic immunoglobulin light chain amyloidosis (AL) was the most common (49%) type, followed by (24.5%) wild‐type transthyretin amyloidosis (H‐TTR) (24.5%), undetermined cases (21%), and reactive systemic amyloidosis (AA) (6.1%). There were mucocutaneous manifestations in 34.7% of cases, mostly multiple myeloma‐related AL (ALMM). Head and neck was the most often affected site (38.2%), and purpuric macules were the most common morphology (44.1%). Mucocutaneous affectation was predominantly observed in AL (50.0%) compared to other types (20.0%) of amyloidosis (P = 0.01). Likewise, involvement of organs was also significantly different among the diverse amyloidosis types (P < 0.05). The most frequent comorbidities were hypertension (18.3%) and hypothyroidism (18.3%).
Conclusion
The clinical spectrum of manifestations in amyloidosis is wide. Involvement of skin and mucosa in amyloidosis is common; significant differences were observed concerning distribution of mucocutaneous amyloid manifestations among the different types of amyloidosis.
Background
The purpose of the study was to evaluate the clinical patterns of atrophy of the filiform papillae (FP) of the tongue and their relationship with the serum levels of iron and vitamin B12 ...among patients with systemic diseases, in a tertiary care center.
Methods
A cross‐sectional, analytical, research study was designed. A systematic tongue examination was performed to evaluate the presence and clinical patterns of FP atrophy. We collected epidemiologic, clinical, and laboratory data. Statistical analysis included χ2 test, Fisher's exact test, Kruskal–Wallis test, and a logistic regression analysis.
Results
A total of 87 patients (83.9% females) were included median age = 55 (range 20–89) years. Endocrinopathy (60.9%) was the most frequent comorbidity. We found atrophy of the FP in 90.8% of the patients; the atrophy was mild in 83.5% of the cases, and severe in 16.5%. The most common atrophic patterns were as follows: focalized in 64 (73.6%) cases, “U”‐shaped pattern in 60 (69%), and generalized in 30 (34.5%). Geographic tongue and median rhomboid glossitis were observed in 12 (13.8%) and 11 (12.6%) subjects, respectively. Lower titers of serum iron were detected in cases with focal (median = 71 vs. 110 mcg/dl) and generalized (median = 55 vs. 78 mcg/dl) FP atrophy (P = 0.03 and P = 0.009, respectively), than their counterparts. The presence of symptomatology was related to the focal pattern of atrophy (P = 0.038).
Conclusions
A high frequency of filiform papillary atrophy of the tongue was observed in patients with comorbidities. Some atrophic patterns of the tongue were significantly associated with certain medical conditions.
Cutaneous drug-induced reactions are immune-mediated responses that can lead to life-threatening diseases such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson ...syndrome, and toxic epidermal necrolysis, collectively known as severe cutaneous adverse reactions (SCARs). Unfortunately, they cannot be predicted during drug development, and, at present, a prognostic biomarker is not available nor are validated in vitro assays for diagnosis. Thus, by using proteomic and microarray miRNA analysis, the cargo of extracellular vesicles obtained from SCARs patients was analyzed and correlated with the severity of the reaction. Confirmatory assays using Western blot and qRT-PCR were performed to validate findings, and bioinformatic tools were used to establish the correlation between protein and miRNAs expression between groups. The proteomic analysis showed an increase in the amount of pro-inflammatory proteins, von Willebrand factor, and C-reactive protein and a decrease in anti-inflammatory and protective proteins in the SCARs group compared with the control group. Additionally, histone protein H2A was enriched in DRESS patients. APO1 and SERPINA4 proteins, highly increased in the control group but absent in the SCARs group, are the target of several overexpressed miRNAs, suggesting that the regulation of these proteins might involve gene silencing and protein repressing mechanisms in the severe patients. According with previous reports showing its presence in plasma and T-cells, microRNA miR-18 was upregulated in extracellular vesicles obtained from the most severe patients. Determination of the unique cargo associated with different disease conditions will help to understand the pathophysiology of these complex reactions and might help to develop novel biomarkers for life-threatening iatrogenic cutaneous disease.
Dysregulation in the expression of microRNAs (miRNAs), single-stranded RNAs which regulate gene expression, has been associated with diseases such as Stevens–Johnson syndrome (SJS)/toxic epidermal ...necrolysis (TEN), although their cellular origin has not been explored. Thus, the focus of this work was to study expression patterns of reported miRNAs involved in T-cell activation following drug-specific stimulation in peripheral blood mononuclear cells (PBMCs) and drug-specific CD4+ T-cell clones (TCC) from patients with different cutaneous manifestations of delayed-type drug hypersensitivity reactions. CD4+ T-cells from hypersensitive patients were stimulated to proliferate, secreted cytokines (IFN-γ and IL-22), cytolytic molecules (Granzyme B) and up-regulate miRNAs 24 to 48 h after drug exposure. Carbamazepine-specific CD4+ T-cells that proliferated to the greatest extent and secreted the highest levels of IFN-γ showed an up-regulation of miR-18a and miR-155. In contrast, piperacillin-specific CD4+ T-cells displaying high expression of miR-9 and miR-21 showed an association with the extent of proliferation, but not IFN-γ secretion. MiR-155 up-regulation was detected in PBMCs from all hypersensitive patients 24 h after drug treatment, while miR-18a and miR-21 expression was up-regulated after 48 h. These findings demonstrate that miRNAs are expressed during drug-specific CD4+ T-cell activation and shows a new regulation path for drug hypersensitivity reactions.
Background
Dermatologic diseases are common in patients being treated in intensive care units (ICU). However, due to the seriousness of the patient's condition, skin diseases take a backseat, ...although these are sometimes the cause of the greatest deterioration. Very few studies focusing on these dermatoses have been undertaken.
Objectives
This study aimed to determine the prevalence and spectrum of dermatological disorders in patients treated in a medical ICU of a tertiary care centre.
Methods
This was a descriptive study conducted over a period of 8 months. All the patients admitted to the medical ICU were examined for the presence of any pre‐existing or newly developed dermatological disorder. Dermatological disorders were initially classified into infective and noninfective. Patients with dermatological findings were classified into two groups: those who survived and those who died; they were compared with each other with respect to age and sex distribution, length of ICU stay and dermatological findings.
Results
Out of 776 cases admitted to the ICU during the study period, dermatological disorders were observed in 164 (21.13%) cases. Life‐threatening dermatological disorders were seen in 3.05% of cases. Twenty‐nine (17.68%) patients with dermatological findings died. Among these cases, infectious dermatological disorders were significantly less common, while no significant difference was observed for reactive dermatological disorders.
Conclusions
Dermatological disorders in ICU are common and have a wide spectrum. They often need treatment and may be indicative of underlying potentially fatal systemic illness. Besides, a subset of cutaneous lesions may develop in response to various medical interventions, immunosuppression and immobility. Knowledge of such dermatoses is thus essential, both for the intensivist and dermatologist.
The study unveiled the prevalence of dermatological ailments among intensive care unit (ICU) patients, often overlooked due to the severity of their conditions. Dermatological disorders were noted in 21.13% of ICU admissions, with 3.05% deemed potentially fatal. Mortality stood at 17.68% among patients with such findings. Dermatology in the ICU is pivotal for early detection and proper management of these conditions, indicative of underlying systemic illnesses. Collaborative efforts between intensivists and dermatologists are indispensable for enhancing patient care in the ICU.
We compared the chemokine/receptor expression in skin biopsies of discoid (SLE/DLE) and subacute lupus (SLE/SCLE) and correlated it with tissue and circulating effector CD4 T cells/regulatory cells. ...Skin biopsies and peripheral blood from 9 active SLE/DLE patients, 9 SLE/SCLE patients, 5 control SLE patients without cutaneous lesions and 10 control healthy donors were included. Clinical skin activity was measured by Cutaneous Lupus Erythematosus Disease Area and Severity Index scoring, and systemic activity was measured by a modified SLEDAI-2K excluding the cutaneous items. Pain and pruritus were evaluated by a 10-point visual analogue scale. To determine the frequencies of CXCL-10/CXCR3-, CCL2/CCR2-, CCL17/CCR4-, CCL20/CCR6-, CCL27/CCR10-, CXCL8/CXCR1-, CXCL13/CXCR5-, IL-22-, CD4/IL-17A-, CD4/IL-4-, CD4/IFN-γ-, CD123/IDO-, CD25/Foxp3-, and CD20/IL-10-expressing cells, double immunostaining procedures were performed. Circulating CD4+/CD161-/IL-22+, CD4+/CD161+/IL-17+, CD4+/CD25-/IL-4+, CD4+/CD25-/IFN-γ+, CD4+/CD25hi/Foxp3+, CD3+/CD19+/CD38hi/IL-10+, and CD123+/CD196+/IDO + cells were analyzed by flow cytometry.
In the tissue, CXCL10, CXCR5, and CCL20 expression and IL-22+, CD4+/IL-17+, CD4+/IFN-γ + and CD123+/IDO + cell percentages were increased in SLE/DLE versus SLE/SCLE. Circulating CD4+/CD161-/IL-22+, CD4+/CD161+/IL-17+, CD4+/CD25-/IFN-γ+, CD19+/CD38hi/IL-10 + and CD123+/CD196+/IDO + cell percentages were higher in SLE/DLE versus SLE/SCLE. In the tissue, we found positive correlations between CXCR3 and CD4+/IL-17 + cells; CCR2 and CD4+/IFN-γ + cells; and CCR10 and CD123+/IDO + cells in the SLE/DLE patients and between CXCL13 and CD20+/IL-10 + cells in the SLE/SCLE patients. In the peripheral blood, we determined positive correlations between CXCR5 and CD4+/CD25-/IFN-γ + cells; CCL17 and CD4+/CD161-/IL-22 + cells; and CCL17 and CD4+/CD161+/IL-17 + cells in the SLE/DLE patients and between CXCR5 and CD3+/CD19+/CD38hi/IL-10 + cells; CCR2 and CD4+/CD25hi/Foxp3 + cells; and CXCR1 and CD4+/CD25hi/Foxp3 + cells in the SLE/SCLE patients. Positive correlations between the pain score and the expression of CCL2 and CCR6 expression were found in the SLE/SCLE patients.
In conclusion, the correlations between the expression of chemokines/receptors and subpopulations of effector/regulatory cells showed differential responses among the cutaneous pathologies.
Drug reaction with eosinophilia and systemic symptoms is a severe adverse drug reaction, with a reported mortality of 10%. Long-term outcomes involve organic failure and autoimmune diseases in some ...populations.
To evaluate the clinical prognosis of patients with drug reaction with eosinophilia and systemic symptoms.
We conducted a retrospective review at a referral hospital in Mexico City in a period of 22 years (1992-2013), looking up for records with diagnosis of DRESS according to RegiSCAR criteria. Clinical characteristics, organ failures, culprit drugs, treatment, and short and long-term sequelae were analyzed.
We found 11 patients with diagnosis of drug reaction with eosinophilia and systemic symptoms syndrome, 7 female and 4 male, with a median age of 22 years-old; 9 had maculopapular rash and 2 were erythrodermic. Affected organs were liver (8/11), kidney (6/11) and hematologic disorders (8/11). The most common culprit drugs were antiepileptic (63%). Systemic corticosteroids were given to 8 patients, being pyelonephritis (1/8) and pneumonia (2/8) the adverse events of this therapy. Long-term sequelae were 1 patient with renal failure, 1 patient with chronic anemia; and 2 patients developed autoimmune diseases (one autoimmune thyroid disease and another one with autoimmune thyroid disease and autoimmune hemolytic anemia). Study limitations: The retrospective nature of the study and the limited number of patients with drug reaction with eosinophilia and systemic symptoms.
Drug reaction with eosinophilia and systemic symptoms syndrome has been linked to the development of chronic organ failure. We found two young patients who developed autoimmune diseases in the short term. Patients with drug reaction with eosinophilia and systemic symptoms should have a long-term monitoring for signs or symptoms suggestive of an autoimmune disease.
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