Cold agglutinin disease is an autoimmune haemolytic anaemia related to a clonal B-cell disorder of the bone marrow. Haemolysis is complement-dependent, while acrocyanosis is monoclonal agglutinin-dependent. Established therapies target the clonal B cells or the classical complement pathway. Treatment can be tailored based on clinical phenotypes.

OBJECTIVE: This study aims to report the clinical, laboratory, and imaging manifestations of juvenile Sjögren’s disease (SjD) and highlight the role of large salivary gland ultrasound and small salivary gland biopsy for the purpose of diagnosis and classification in this age group. BACKGROUND: Currently, there are no unified classification criteria for juvenile SjD, and pediatric-specific literature is scarce. The current literature lacks validated pediatric-specific classification and diagnostic tools. Many tests used in adult classification criteria are not routinely assessed in children because they can be difficult to perform on younger patients and lack age-specific thresholds for abnormal results. This study aims to help build the foundation for future proposals to specifically classify SjD in the pediatric age group. METHODS: This was a single-center exploratory pilot retrospective study of medical records of patients diagnosed with juvenile SjD over the past five years. RESULTS: Fifteen patients with juvenile SjD were included. The median age of disease onset was 11.5 years (range 8.5–17.5 years), and the median age at diagnosis was 12.5 years (range 8.5–17.5 years). Ten patients had primary SjD, and five patients had SjD secondary to systemic lupus erythematosus and limited scleroderma. The clinical manifestations at onset included musculoskeletal manifestations (n = 9), recurrent parotitis (n = 7), mucocutaneous manifestations (n = 6), cervical lymphadenopathy (n = 6), Raynaud’s phenomenon or acrocyanosis (n = 3), fever (n = 2), dysphagia (n = 2), respiratory symptoms (n = 2), and sicca manifestations (n = 2). One patient with primary SjD presented with life-threatening macrophage activation syndrome. Sarcoidosis, IgG-4-related disease, and relevant infections were ruled out in all patients. Anti-SSA antibodies were positive in 13/15 patients. All patients had abnormal large salivary gland ultrasound findings, including heterogeneous echogenicity (14/15), gland enlargement (14/15), hyperemia (11/14), cystic changes (10/15), cervical lymphadenopathy (8/15), and intraductal mucus plugging or calcifications (3/15). Small salivary gland biopsies from 13/13 patients were negative for granulomas and malignancies and revealed lymphocytic sialoadenitis with a focus score of ≥1. CONCLUSION: Recurrent parotitis and scarce sicca manifestations are two distinct clinical features of juvenile versus adult SjD. Large salivary gland ultrasound study is a promising practical tool that should be considered in suspected juvenile SjD patients. These clinical and imaging features should be considered in any proposed classification criteria for juvenile SjD.

The article presents a clinical case of secondary erythromelalgia in a comorbid patient with antiphospholipid syndrome, accompanied by burning pain, hyperemia and swelling of the lower extremities. A comprehensive examination involving a neurologist, dermatologist, and rheumatologist was conducted to establish the diagnosis and select the optimal therapy. Significant clinical improvement in the patient's condition is demonstrated against the background of pregabalin therapy. The importance of a multidisciplinary approach and the difficulty of diagnosis due to the lack of specific examination methods and insufficient awareness of doctors about this disease are emphasized. The described case demonstrates the need for a personalized approach to managing patients with erythromelalgia to improve their quality of life.

Ethylmalonic encephalopathy is a rare autosomal recessive mitochondrial disorder caused by biallelic pathogenic variants in ETHE1, the gene encoding mitochondrial persulfide dioxygenase, an enzyme crucial for hydrogen sulfide (H2S) detoxification. Loss of this enzyme results in H2S accumulation, cytochrome c oxidase inhibition, oxidative stress, and disrupted energy metabolism. Clinically, ethylmalonic encephalopathy manifests during early infancy with developmental delay, hypotonia, progressive encephalopathy, seizures, chronic diarrhea, and microvascular abnormalities such as petechiae and acrocyanosis. Fewer than 100 cases have been reported globally, mostly among Mediterranean and Arab populations, with scarce data from Latin America. We report the first documented case of ethylmalonic encephalopathy in a Mexican patient. The affected male infant, born to healthy nonconsanguineous parents of indigenous Maya origin from Yucatán, presented at 2 weeks of age with persistent hemorrhagic diarrhea, followed by metabolic acidosis, hyperammonemia, hyperlactatemia, elevated C4-acylcarnitine, and increased urinary ethylmalonic acid. Neurological findings included developmental delay, hypotonia, and myoclonic epilepsy. Whole-exome sequencing revealed a homozygous frameshift pathogenic variant in ETHE1 (NM_014297.5):c.19_20dup (p.Val8Glyfs*7), predicted to introduce a premature stop codon and abolish protein function. Despite targeted interventions-antiepileptic therapy, ammonia-lowering treatment, and metabolic support-the patient's condition progressively worsened, culminating in death at 15 months after metabolic decompensation and brain death. This case broadens the known mutational spectrum of ETHE1 by identifying a previously unreported pathogenic variant and underscores the need to include ethylmalonic encephalopathy in the differential diagnosis of infants presenting with chronic diarrhea, vascular lesions, and neurological deterioration, even in regions where the condition is not typically observed.

This report describes the first documented case of concurrent cold agglutinin disease (CAD) and acquired hemophilia A (AHA) in a 53-year-old male presenting with recurrent hematuria, hematemesis, and cold-induced acrocyanosis. Diagnostic findings included severe anemia with hemoglobin of 61 g/L, markedly prolonged activated partial thromboplastin time (aPTT, 88.6 s), critically reduced factor VIII activity (1.4%), a factor VIII inhibitor titer of 3.6 Bethesda units, and an elevated cold agglutinin titer of 1:320. Initial immunosuppression with corticosteroids and cyclophosphamide failed to improve either the coagulopathy or hemolytic anemia, consistent with the recognized poor response of CAD to steroid therapy. Clinical deterioration occurred during steroid tapering, complicated by hospital-acquired pneumonia. Administration of rituximab (375 mg/m[2] weekly for 4 weeks) resulted in simultaneous resolution of both autoimmune processes, with normalization of coagulation parameters and significant improvement in hemoglobin levels. This outcome aligns with established evidence supporting B-cell targeted therapy for autoimmune hematologic disorders. The case highlights the diagnostic challenges posed by overlapping autoimmune hematologic conditions and demonstrates the therapeutic potential of rituximab in simultaneously addressing both coagulation and hemolytic pathologies. It further underscores the importance of targeted treatment strategies that minimize infection risks associated with broad immunosuppression. This unique presentation advances our understanding of shared autoimmune mechanisms in hematologic disease and supports the use of early B-cell-directed therapy in complex autoimmune hematologic conditions.

Acrocyanosis is a peripheral vascular disorder characterized by bluish discoloration of the distal extremities. While drug-induced acrocyanosis has been associated with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and other medications, venlafaxine has not previously been reported as a causative agent. We present a case of a 40-year-old female who developed acute acrocyanosis following the initiation of venlafaxine for insomnia. Symptoms appeared within 24 h of intake and progressively involved the hands and feet. Laboratory investigations were largely unremarkable, and other potential causes, including Raynaud's phenomenon and vasculitis, were excluded. Discontinuation of venlafaxine led to complete resolution of symptoms within a week, confirming a strong temporal association. This case underscores the need for clinical awareness of venlafaxine-induced acrocyanosis as a rare but possible adverse effect, emphasizing timely recognition and management to prevent complications.

Catatonia is a psychomotor syndrome that can present secondary to mood and psychotic disorders, other medical conditions, antipsychotic use, and alcohol withdrawal (Rasmussen et al., World Journal of Psychiatry, 6:391-398, 2016). In addition, acute and chronic trauma are increasingly recognized as a substrate for catatonia (Dhossche et al., Acta Psychiatrica Scandinavica, 125:25-32, 2012). Catatonia is a clinical diagnosis that relies on standardized examination of the patient. The Pediatric Catatonia Rating Scale (PCRS) was modified from the Bush Francis Catatonia Rating Scale and validated in children and adolescents (Benarous et al., Schizophrenia Research, 176:378-386, 2016). Changes included the addition of urinary incontinence, schizophasia and acrocyanosis; and withdrawal was separated into refusal to eat or drink and social withdrawal (Benarous et al., Schizophrenia Research, 176:378-386, 2016). In both pediatric and adult patients, catatonia must be differentiated from other movement disorder emergencies such as serotonin syndrome and neuroleptic malignant syndrome, which can also present with altered mental status and autonomic dysfunction (Rajan et al., Seminars in Neurology, 39:125-136, 2019). In pediatric patients, catatonia may be the genuine diagnosis in cases of Resignation Syndrome and Pervasive Refusal Syndrome (Sallin et al., Frontiers in Behavioral Neuroscience, 10(7), 2016; Ngo and Hodes, Clinical Child Psychology and Psychiatry, 25:227-241, 2019). The literature on pediatric catatonia is scarce but nevertheless expanding. Herein, we contribute to the literature by reporting four complex cases of pediatric catatonia that appear to have been triggered by a traumatic event and further reviewing the role of acute and chronic trauma in the presentation of pediatric catatonia.

BACKGROUND: Subungual splinter hemorrhages may represent an expression of infective endocarditis as well as autoimmune diseases or neoplasms. Anti-SAE1 autoantibody is directed against a small ubiquitin-like modifier-activating enzyme that plays a role in regulating transcription, cell cycle, and apoptosis. It is specific for dermatomyositis with skin rash and mild muscle involvement, and it can be associated with cancer. CASE REPORT: We describe the case of a patient who developed subungual splinter hemorrhages and acrocyanosis. Infections were excluded, and autoimmunity resulted in anti-SAE1 autoantibodies. A cancer screening found a high-grade urothelial carcinoma. The splinter hemorrhages disappeared after the carcinoma enucleation. CONCLUSIONS: Our case describes an atypical onset of anti-SAE1 dermatomyositis with splinter hemorrhages, potentially linked to urothelial cancer. This highlights the importance of comprehensive cancer screening in patients with unusual dermatomyositis presentations.

Acrocyanosis and gangrene are rare but serious manifestations of CAS caused by MP infection in children. These symptoms may lead to severe complications if not managed appropriately, highlighting the need for clinicians to remain vigilant and provide proper supportive care. In the case we discussed, the administration of FFP, plasmapheresis, corticosteroids, and IVIG led to a satisfactory improvement in the patient's condition.

Paraneoplastic acral vascular syndrome (PAVS) is a rare condition characterised by signs of digital ischaemia, including Raynaud's phenomenon, acrocyanosis and digital gangrene, in the context of an underlying neoplastic process. Prompt recognition of this syndrome, as well as accurate identification and classification of the associated neoplastic condition, are crucial.This report describes the case of a woman diagnosed with PAVS secondary to stage IV non-small cell lung adenocarcinoma harbouring a Kirsten Rat Sarcoma viral homolog oncogene (KRAS) G12A mutation (p.Gly12Ala).

Symmetrical peripheral gangrene (SPG) is an exceptionally uncommon complication of malaria, predominantly linked with Plasmodium falciparum and mixed infections. We report a 41-year-old female who presented to a tertiary care centre of eastern India in 2022 with complaint of fever with chills and rigor for 4 days along with pain and acrocyanosis of distal portions of bilateral upper and lower limbs for last 2 days. Investigations revealed anaemia and neutrophilic leucocytosis with thrombocytopaenia. The peripheral smear revealed trophozoites of P. vivax and the malaria rapid diagnostic test confirmed the presence of P. vivax antigen. D-dimer and fibrin degradation product was elevated and prothrombin time and activated partial thromboplastin time were prolonged; arterial colour doppler of all 4 extremities were within normal limits. A diagnosis of P. vivax malaria was made complicated with disseminated intravascular coagulation leading to SPG.