Anti-synthetase and myelodysplastic syndromes with deep morphea: an example of shared immunopathogenesis? A case-based review.

Anti-synthetase syndrome (AS) is a subset of idiopathic inflammatory myopathy (IIM) characterized by the presence of anti-aminoacyl-transfer RNA synthetase accompanied by myositis, interstitial lung disease and other clinical features. According to a recent multicentric study, 31% of AS patients present skin lesions compatible with dermatomyositis, but sclerodermiform features are rare. Therefore, we aimed to report the case of a patient with simultaneous diagnosis of AS, deep morphea, vasculitic neuropathy, and myelodysplastic syndrome and review the current literature regarding these uncommon associations. A 57 year old man with axial and symmetrical proximal muscle weakness, skin thickening and B symptoms, later diagnosed with PL7 + AS, deep morphea, myelodysplastic syndrome (MDS) and vasculitic neuropathy documented by histopathologic studies and immunologic assessments. Since both AS and deep morphea share the vasculopathic changes and type II interferon-induced inflammation, we hypothesize that they may share pathogenic mechanisms. The muscle biopsy of the patient was consistent with AS and showed focal neutrophil infiltration. The patient received intensive immunosuppressive therapy for AS and vasculitic neuropathy, with high dose steroids, intravenous immunoglobulin (IVIg) and rituximab. Nonetheless, he suffered an unfavorable evolution with a fatal outcome due to septic shock. Albeit sclerodermiform features are rare in patients with AS, we propose a pathogenic link among AS, deep morphea and the autoimmune/autoinflammatory signs of MDS. The vasculopathic changes along with the activation of the innate and adaptive immune system leading to the production of proinflammatory cytokines may have been one of the contributing factors for the coexisting diagnosis of the patient.

Pseudolymphomatous Cutaneous Angiosarcoma Presenting With Persistent Firm Facial Edema in a Patient With Systemic Sclerosis.

ABSTRACT: Pseudolymphomatous cutaneous angiosarcoma (cAS) is a rare subtype characterized by a prominent lymphocytic infiltrate, posing diagnostic challenges due to its resemblance to lymphoid neoplastic processes. We present a novel case highlighting the clinical and histopathological features, notably its association with persistent firm facial edema in a patient with systemic sclerosis (SSc). A 47-year-old woman with a 21-year history of SSc presented with firm palpebral edema evolving to involve the entire face and cervical region over six months. Diagnostic imaging revealed inflammatory changes in orbital regions, supradiaphragmatic lymphadenopathies, and lytic lesions. Skin biopsy demonstrated a diffuse neoplasm with vascular channels and solid areas, accompanied by dense lymphocytic proliferation. Pseudolymphomatous cutaneous angiosarcoma, a rare malignant neoplasm, exhibits variable clinical presentations and rapid progression. Histologically, it manifests as irregularly shaped vascular channels lined by prominent endothelial cells. Immunohistochemistry, particularly markers such as v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG), aids in diagnosis. Notably, this case marks the first presentation of cAS with persistent facial edema in SSc, highlighting the association between SSc and cancer risk. This case underscores the diagnostic challenges posed by cAS and emphasizes the importance of early detection for optimal patient outcomes. Further understanding of its association with autoimmune disorders such as SSc is crucial for comprehensive management strategies.

Granulomatous Panniculitis as an Initial Manifestation of Sjögren Syndrome.

ABSTRACT: A 65-year-old woman presented with unexplained weight loss, recurrent fever, and a dermatosis with painful nodules on the extremities. Biopsies showed focal lobular panniculitis with neutrophilic microgranulomas. Comprehensive investigations ruled out infection and hematologic and solid organ neoplasms. Laboratory results showed anti-Ro/SSA and anti-La/SSB antibody positivity, and elevated inflammatory markers. Dry mouth and eye were confirmed. The diagnosis of Sjögren syndrome with cutaneous panniculitis was established. Prednisone treatment with 30 mg/d resulted in remission of fever and pain improvement. This case emphasizes Sjögren syndrome as an autoimmune disease with multiple cutaneous manifestations and highlights its association with granulomatous panniculitis.

Sweet Syndrome as a Herpetiform Mimic: A Diagnostic Challenge.

ABSTRACT: The authors present a singular case of Sweet syndrome (acute febrile neutrophilic dermatosis) manifesting with an unusual herpetiform clinical presentation, underscoring the imperative for its inclusion in differential diagnoses of herpetic infections. A 26-year-old female patient with a systemic lupus erythematosus history presented with facial edema, hyperthermia, cephalalgia, and polyarticular pain. Dermatological examination revealed clustered, vesicle-like papules on erythematous, edematous skin, mimicking herpetic infection. Elevated acute-phase reactants and urine anomalies were noted. Histopathology confirmed Sweet syndrome, characterized by superficial and deep neutrophilic dermatitis, karyorrhexis, and papillary dermal edema. The patient responded to corticosteroid therapy and a brief antibiotic course, resolving both systemic and cutaneous symptoms. This case is remarkable for its atypical herpetiform presentation, a clinical rarity in Sweet syndrome, challenging the conventional diagnostic process. It emphasizes the necessity of considering Sweet syndrome in differential diagnoses when encountering herpetiform lesions, particularly in patients with autoimmune backgrounds. This case contributes significantly to the understanding of Sweet syndrome's clinical variability and highlights the critical role of thorough clinicopathological evaluation in achieving accurate diagnosis in complex dermatological disorders.

Clinical atrophy patterns of filiform papillae of the tongue and their relationship with the serum levels of iron, vitamin B12 and folic acid in patients with systemic diseases.

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.

[Anti-MDA5 dermatomyositis. Literature review]. / Dermatomiositis anti-MDA5. Revisión de la literatura.

Dermatomyositis positive anti-melanoma differentiation-associated gene 5 (anti-MDA5 DM) is a rare disease that represents less than 2%. The prevalence of anti-MDA5 DM ranges from 7 to 60%, with higher prevalence in Asian (11-60%) and women. The clinical picture may be variable and is accompanied by the typical features of dermatomyositis, such as periorbital heliotrope (blue-purple) rash with edema, erythematous rash on the face, or the anterior chest (in a V-sign), and back and shoulders (in a shawl sign), violaceous papules or plaques located on the dorsal part of the metacarpophalangeal or interphalangeal joints, which are pathognomonic by definition; yet, one of the most striking signs is the painful ulceration skin that is found in 82% of cases, which is deep and in punching holes or showing hyperkeratotic crusts. For diagnosis is necessary the typical DM rashes (Gottron's papules or Gottron's sign and heliotrope rash), along with either an "interface dermatitis" skin pathology or evidence of myositis or a MSA (myositis-specific autoantibodies). Immunoprecipitation is the gold standard method to detect MSA. Combinations of glucocorticoids and immunosuppressants are used for treatment; besides, it is necessary the detection of rapidly progressive interstitial disease (RP-ILD) with a high-resolution CT because of its high association with fatal prognosis.

La dermatomiositis positiva contra el gen 5 asociado a la diferenciación de melanoma (DM anti-MDA5) es una enfermedad rara que representa menos del 2%. La prevalencia de DM anti-MDA5 varía de 7 a 60%, con mayor prevalencia en asiáticos (11-60%) y mujeres. El cuadro clínico es muy variado y se acompaña por las características típicas de dermatomiositis, como la eritema en heliotropo, con edema, exantema eritematoso en la cara o la parte anterior del tórax (signo de V) y en la espalda y los hombros (signo del chal), las pápulas de Gottron en la parte dorsal de las articulaciones metacarpofalángicas o interfalángicas, que son patognomónicas por definición, pero uno de los signos más llamativos es la ulceración cutánea dolorosa que se encuentra hasta en un 82% de los casos, es profunda y en sacabocados muestran costras hiperqueratósicas. Para el diagnóstico son necesarias las erupciones típicas de la DM (pápulas de Gottron o signo de Gottron y erupción de heliotropo), junto con una patología cutánea de "dermatitis de interfase" o evidencia de miositis o un MSA (autoanticuerpos específicos de miositis). La inmunoprecipitación es el método de referencia para detectar MSA. Para su tratamiento se usan combinaciones de glucocorticoides e inmunosupresores; ademas, es necesaria la detección de enfermedad intersticial rápidamente progresiva (RP-ILD) con tomografía computarizada de alta resolución por su alta asociación con un pronóstico fatal.

Predictive factors associated with the persistence of chest pain in post-laparoscopic myotomy and fundoplication in patients with achalasia.

Background: Episodic angina-like retrosternal pain is a prevalent symptom for achalasia patients pre- and post-treatment. The cause of postoperative chest pain remains poorly understood. Moreover, there are no reports on their predictive value for chest pain in the long-term post-treatment. The effect of laparoscopic Heller myotomy (LHM) and fundoplication techniques (Dor vs. Toupet) is unclear. Methods: We analyzed a cohort of 129 achalasia cases treated with LHM and randomly assigned fundoplication technique. All the patients were diagnosed with achalasia by high-resolution manometry (HRM). Patients were followed up at 1-, 6-, 12-, and 24-month post-treatment. We implemented unadjusted and adjusted logistic regression analyses to evaluate the predictive significance of pre- and post-operative clinical factors. Results: Preoperative chest pain with every meal was associated with an increased risk of occasional postoperative chest pain [unadjusted model: odds ratio (OR) = 12, 95% CI: 2.2-63.9, P = 0.006; adjusted model: OR = 26, 95% CI: 2.6-259.1, P = 0.005]. In type II achalasia, hypercontraction was also associated with an increased risk of chest pain (unadjusted model: OR = 2.6 e9 in all the patients). No significant differences were associated with age, type of achalasia, dysphagia, esophageal shape, and integrated relaxation pressure (IRP) with an increased risk of occasional postoperative chest pain. Also, there was no significant difference between fundoplication techniques or surgical approaches (e.g., length of myotomy). Conclusion: Preoperative chest pain with every meal was associated with a higher risk of occasionally postoperative chest pain.

Nail Changes in People Living with Human Immunodeficiency Virus: Observational and Cross-Sectional Study in a Third-Level Hospital.

Introduction: Nail changes in people living with human immunodeficiency virus (HIV) have been scarcely reported. The aim of this study was to establish the frequency and characteristics of nail alterations observed in adults with HIV infection in a third-level hospital in Mexico. Method: Observational and cross-sectional study carried out in 205 patients receiving care at the HIV/AIDS Clinic of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) in Mexico City. We performed a nail and iconographic assessment of both hands and toenails. We collected information of demographic and clinical variables, as well as drugs use, and antiretroviral treatment used by the participants through a questionnaire and from medical records. We performed direct cytological examinations and nail mycological cultures in participants with symptoms of onychomycosis. Results: The participants were predominantly male patients (91.2%), with a mean age of 41 (range 21-78) years, under antiretroviral therapy (91.2%), with a suppressed viral load (78.5%) and mean CD4+ lymphocyte count of 379.5 (range 20-1,162) cells/µL. Fitzpatrick's IV phototype was prevailing in the studied population (70%). Nail changes were documented in 72.2% of the patients; being pigmentary changes (37.1%) and trauma (30.7%) the most frequent. Onychomycosis was observed in 26.3%; with total dystrophic onychomycosis as the most frequent clinical variant (68.5%). We obtained fungal isolates in 59.3% of participants and Candida parapsilosis was the most frequent of these (37.5%). Conclusions: We observed a high prevalence of nail changes with very diverse etiology, as well as a variety of nondermatophytic yeasts and molds isolates associated with cases with onychomycosis. These findings reinforce and confirm the need for routine nail examination and stress the importance of medical personnel working with people living with HIV to have broad knowledge of nail pathology.

Pain Management in Patients with Severe Pemphigus Vulgaris.

To describe the pain management and clinical course of patients with severe Pemphigus Vulgaris (PV) admitted to a third-level Intensive Care Unit (ICU). This was a retrospective cohort study conducted in the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán over the period 2013-2020. Study population comprised patients with severe PV admitted to the ICU. Eleven patients with severe PV were included. Mean age of presentation was 43.6 years. Percentage of the total body surface area affected ranged from 70 to 85% (mean: 80%). Visual Analogue Scale was used for pain assessment upon admission. Nine patients (72%) reported a 10/10 pain. The median Morphine Equivalent Daily Dose was 200 mg (range: 90-518 mg). Mortality was 27% during the ICU stay. One patient (9%) continued to experience severe pain and consume opioids after discharge. PV is a life-threatening disease characterized by painful, persistent erosions and ulcers. Integrated and multidisciplinary approach is often required. Opioids remain the mainstay for acute pain control in patients with severe PV. Biological, psychological, and social factors influence patients' daily opioid requirements and dose escalation. Successful pain management contributes to improving the quality of life, and the suppression and remission of PV.

Extracellular Vesicles from Human Plasma Show a Distinctive Proteome and miRNome Profile in Patients with Severe Cutaneous Adverse Reactions.

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.

Cutaneous manifestations are frequent and diverse among patients with rheumatoid arthritis and impact their quality of life: a cross-sectional study in a cohort of patients with recent-onset disease.

INTRODUCTION/OBJECTIVES: Cutaneous involvement is often overlooked in rheumatoid arthritis (RA). We described cutaneous findings in outpatients attending a recent-onset cohort and identified factors associated with skin involvement and reduced (R) dermatological quality of life (DQoL). METHODS: Skin and rheumatological examinations were performed in 122 patients. DQoL was assessed through the Dermatology Life Quality Index (DLQI). Skin findings were classified as RA-specific and RA-nonspecific. Multiple regression analysis identified factors associated to skin involvement and RDQoL (DLQI score > 1). RESULTS: Patients were middle-aged females (91%), with a 1-year mean disease activity score in 28 joints as 2.0 (interquartile range: 1.5-2.6). There were 94 (77%) patients in whom at least one cutaneous finding was observed: 17 (13.1%) had RA-specific findings (all were rheumatoid nodules) and 91 (96.8%) had at least one RA-nonspecific finding, further classified into skin diseases (35.2%), hair diseases (20.9%), and skin-related signs (76.9%, among whom 94.3% had xerosis). Age (odds ratio [OR]: 1.054, 95% confidence interval [CI]: 1.015-1.094) and skin-health concerns (OR: 5.657, 95% CI: 1.771-18.070) were associated with cutaneous involvement, whereas increased age and DLQI score were associated with a higher number of skin findings/patient. There were 29 patients (24.2%) with RDQoL, which were associated with the Short Form-36 emotional component (OR: 0.955, 95% CI: 0.923-0.988) and the number of skin findings/patient (OR 2.873, 95% CI 1.723-4.791). Pruritus and hair diseases were the individual categories associated with RDQoL. CONCLUSIONS: Cutaneous manifestations are frequent in RA patients and have the potential to impact the emotional component of health-related quality of life. Key Points • Up to 77% of the RA patients with substantial follow-up, from a recent-onset disease cohort, had cutaneous manifestations; these were primarily RA-nonspecific findings, whereas 13.1% had RA-specific findings. • Skin-health concerns and age were associated with cutaneous involvement; meanwhile, increased age and Dermatology Life Quality Index (DLQI) score were associated with a higher number of cutaneous findings/patient. • Reduced dermatological quality of life (RDQoL) was documented in one in four patients and was associated with the SF-36 emotional component and the number of cutaneous findings/patient.

Toenail abnormalities in rheumatoid arthritis patients are associated with radiographic damage and impact disability: a cross sectional study nested within a cohort.

OBJECTIVES: Cutaneous involvement is an extra-articular manifestation of rheumatoid arthritis (RA). This includes nail abnormalities, which are often overlooked. We described nail findings in RA patients currently attending an early arthritis cohort (n=145), and associated them with disease activity and/or damage, as well as patient-reported outcomes. METHODS: A standardised nail examination was performed in 122 patients (84.1% of the cohort), concomitant to the rheumatic assessment. Disability, quality of life and perceived nail-related health were also assessed. Nail findings and their location were recorded and classified according to standardised definitions. Logistic and linear regression models were used to investigate predictors of nail findings and to identify the impact of toenail findings on disability, which was evaluated with the HAQ. Patients consented to participate. RESULTS: Patients were primarily middle-aged females, with median follow-up of 9 years, and had disease under control. Most patients (62.3%) had at least one nail finding and these patients scored lower their nail-related health. The median (IQR) of findings/abnormalities per patient was 3 (2-5) and the number of nails affected per patient was 10 (2-12). Age (OR: 1.04, 95%CI: 1.007-1.074) and erosive disease (OR: 2.26, 95%CI: 1.1-5.1) were associated with nail findings. Toenail involvement was consistently associated with HAQ score out of normal range (OR=3.4, 95%CI=1.24-9.35, p=0.02). There was a linear association between the number of toenails affected and the HAQ score. CONCLUSIONS: Nail abnormalities are common and heterogeneous findings in RA patients; they are associated with erosive damage and impact disability.

Biosimilar medicines for psoriasis. Positioning of the Mexican Academy of Dermatology.

The development and marketing of biosimilars opens a new scenario in the treatment of many pathologies, including psoriasis. This article reflects the position of the Mexican Academy of Dermatology (AMD) on the use of biosimilar medicines for the treatment of psoriasis in Mexico. In summary, the AMD estates that there is sufficient evidence to accept comparability of pharmacokinetics and pharmacodynamics of some biosimilar medicines to adalimumab, infliximab and etanercept; this evidence does not sufficiently support interchangeability or indication extrapolation. It is essential to establish a close pharmacovigilance not only to guarantee compliance with the Cofepris rules in Mexico, but also to facilitate the effective monitoring of the adverse effects of biosimilar medicines. Although the goal of biotechnological drugs is to achieve substantial savings for patients and public institutions, no economic criteria should prevail over rigorous scientific criteria that guarantee maximum therapeutic efficacy and optimum safety for patients.

El desarrollo y comercialización de biocomparables abre un nuevo escenario en el tratamiento de muchas patologías, entre ellas la psoriasis. El presente artículo recoge la postura de la Academia Mexicana de Dermatología (AMD) respecto al uso de medicamentos biocomparables para el tratamiento de la psoriasis en México. En resumen, la AMD establece que existe suficiente evidencia para aceptar la comparabilidad farmacocinética y farmacodinámica entre algunos medicamentos biocomparables al adalimumab, el infliximab y el etanercept; esta evidencia no sustenta suficientemente su intercambiabilidad ni la extrapolación de indicaciones; es fundamental establecer una farmacovigilancia estrecha no solo para garantizar el cumplimiento de las reglas de la Comisión Federal para la Protección contra Riesgos Sanitarios en México, sino para facilitar un seguimiento efectivo de los efectos adversos de los medicamentos biocomparables. Si bien la meta de los medicamentos biotecnológicos es lograr un ahorro sustancial para los pacientes y las instituciones públicas, los criterios económicos no deben anteponerse a criterios científicos rigurosos que garanticen la máxima eficacia terapéutica y la óptima seguridad para los pacientes.

Lamotrigine and its relationship with Stevens-Johnson syndrome and toxic epidermal necrolysis / Lamotrigina y su relación con el síndrome de Stevens-Johnson y la necrólisis epidérmica tóxica

Lamotrigine is an antiepileptic drug that has been widely used for epilepsy, as a mood stabilizer (for type 1 bipolar disorder) and in the management of neuropathic pain, it is used both in monotherapy and in complementary therapy. Considered relatively new, approved by the Food and Drug Administration in 1994, its benefits include a greater margin of safety compared to other anticonvulsants. However, although in a lower percentage, it causes severe adverse skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. A review is made about the probable pathways that trigger this delayed hypersensitivity immune response.

La lamotrigina es un fármaco anticonvulsivo que ha sido utilizado ampliamente para tratar la epilepsia, como estabilizador del ánimo (en casos de trastorno bipolar tipo 1) y en el manejo del dolor neuropático; se usa tanto en monoterapia como en terapia complementaria. Considerado como un medicamento relativamente nuevo, aprobado por la Food and Drug Administration en 1994, dentro de sus beneficios se encuentra un mayor margen de seguridad en comparación con otros anticonvulsivos; sin embargo, aunque en menor porcentaje, es causa de reacciones cutáneas adversas graves, como el síndrome de Stevens-Johnson y la necrólisis epidérmica tóxica. En el presente estudio se realiza una revisión de las probables vías que desencadenan esta respuesta inmunitaria de hipersensibilidad tardía.

Pénfigo vulgar / Pemphigus vulgaris

Resumen: El pénfigo es una enfermedad autoinmunitaria y crónica de incidencia y prevalencia bajas; sin embargo, puede alcanzar mortalidad de incluso 75% sin tratamiento. Existen dos variedades principales: el pénfigo vulgar y el foliáceo, que en términos clínicos se distinguen por la aparición de ampollas en la piel, con afección de las mucosas en los pacientes con pénfigo vulgar. En esta revisión se detalla la epidemiología, causas, fisiopatología y tratamiento de esta enfermedad, con insistencia en la importancia de los esteroides como piedra angular del tratamiento de estos pacientes.

Abstract: Pemphigus is an autoimmune and chronic disease with low incidence and preva- lence. Nevertheless it could reach a 75% mortality rate without treatment. There are two principal types: vulgar pemphigus and foliaceus pemphigus, which are clinically characterized by skin blister appearance, with mucosal affection in patients with pemphigus vulgaris. This review details the epidemiology, etiology, physiopathology and treatment of this disease, remarking the steroid importance as the cornerstone in the management of these patients.