Immune-mediated inflammatory diseases are rare but increasingly reported among patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). Systemic lupus erythematosus (LE) and cutaneous LE associated with MDS/CMML have been rarely described, with atypical features and refractory disease. To provide a comprehensive description of the phenotype and therapeutic responses of LE associated with MDS/CMML and to compare them with idiopathic LE. This retrospective case-control study included nationwide, multicenter data from January 1975 to January 2023. Patients with MDS/CMML who either fulfilled classification criteria for systemic LE or had skin lesions diagnosed as cutaneous LE were included. For MDS/CMML systemic LE, a 2:1 case-control study was conducted with idiopathic systemic LE. Clinical features, centralized skin histopathology, and targeted next-generation sequencing were analyzed. Data were analyzed from May 2022 to June 2025. The clinical, pathological, and molecular features of LE occurring in the setting of MDS or CMML compared with idiopathic LE. Of 24 included patients, 9 (38%) were female, 15 (63%) were male, and the median (range) age at diagnosis was 65 (32-85) years. A total of 19 were diagnosed with systemic LE and 5 with cutaneous LE. The median (range) follow-up was 4.5 (1-31) years. Cutaneous involvement was the most common manifestation of LE (17 [71%]). Chilblain lupus was the predominant subtype (6 [35%]). Compared with idiopathic systemic LE, patients with MDS/CMML-associated LE were older (median [range] age, 65 [32-85] years vs 23 [11-55] years; P < .001), more frequently male (10 [53%] vs 3 [8%]; P = .008), had less kidney involvement (2 [10%] vs 27 [71%]; P < .001), had less articular involvement (7 [36%] vs 37 [97%]; P < .001), and had reduced anti-double-stranded DNA positivity (6 [32%] vs 29 [76%]; P = .001). The underlying hematologic diseases included MDS (16 [66%]) and CMML (8 [34%]), with 22 (92%) classified as lower risk (Revised International Prognostic Scoring System score of 3.5 or less). Centralized histopathological review reclassified 6 skin biopsies (50%) as MDS/CMML cutis. Identical myeloid variants were detected in blood and skin in 6 of 8 patients, supporting a clonal inflammatory process. Standard LE therapies were often poorly effective, while clone-directed therapies (azacitidine or allogeneic hematopoietic stem cell transplant) led to parallel hematologic and LE responses in 5 of 7 patients. In this study, MDS/CMML-associated lupuslike manifestations were a distinct entity mimicking systemic LE or cutaneous LE and characterized by clonal inflammation rather than classic autoimmunity in most cases. Early recognition is important, as treatment may require clone-targeting therapies rather than conventional LE therapy.

Systemic lupus erythematosus (SLE) manifests with a broad spectrum of cutaneous manifestations, including chilblain lupus erythematosus (CHLE), which typically presents as cold-induced, painful acral lesions with specific dermatoscopic and histopathologic features. We describe an unusual case of a 32-year-old woman with established SLE and stage IV lupus nephritis who presented with a five-year history of asymptomatic, recurrent erythematous macules on the palms.  The patient reported no cold sensitivity, pain, or Raynaud's phenomenon, which are hallmark features of classic CHLE. Physical examination revealed irregularly shaped pink macules and patches on the volar aspect of the fingers and thumb base and dorsal hands, sparing the palms. Dermoscopy showed well-demarcated, non-scaling pink macules with nonspecific white dots and sparing of palmar skin lines. Histopathological analysis demonstrated superficial and deep perivascular lymphocytic infiltrates with increased dermal mucin. Direct immunofluorescence revealed granular IgM and IgG deposits at the dermoepidermal junction, supporting a lupus-related process. Although the patient met the histopathologic and minor clinical criteria for CHLE, the absence of cold triggers and pain suggests an atypical presentation of CHLE or a distinct variant of lupus-associated palmar macules. Differential diagnoses, including dermatomyositis and small-vessel vasculitis, were excluded through clinical and laboratory evaluations. This case highlights the clinical variability of cutaneous lupus and the diagnostic challenges posed by palmar lesions that do not strictly adhere to established diagnostic criteria for CHLE. Lupus erythematosus is a multisystem disorder that predominantly affects the skin. There are many types of lupus, including systemic lupus erythematosus (SLE), drug-induced lupus erythematosus, neonatal lupus erythematosus, and cutaneous lupus erythematosus. The most common types of cutaneous lupus erythematosus include acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and chronic cutaneous lupus erythematosus; discoid lupus erythematosus is a subtype of chronic cutaneous lupus erythematosus. Dr James Gilliam described the most commonly used classification of cutaneous lesions in lupus erythematosus. He distinguished lesions as either specific or nonspecific, based on the presence of interface dermatitis on histopathologic examination. Within the category of specific cutaneous lesions, he subdivided these into acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and chronic cutaneous erythematosus. Discoid lupus erythematosus is the most common subset of chronic cutaneous lupus erythematosus. Patients may or may not report photosensitivity, but lesions are frequently photodistributed and often exhibit secondary atrophy or scarring. Most patients with discoid lupus erythematosus do not have significant systemic disease. Discoid lupus erythematosus can also occur as a manifestation of SLE in approximately 20% of patients. Other less common variants of chronic cutaneous lupus erythematosus include hypertrophic lupus erythematosus, tumid lupus erythematosus, lupus erythematosus panniculitis (also known as lupus profundus), chilblain lupus erythematosus, oral discoid lupus erythematosus, and discoid lupus erythematosus lesions on the palms and soles.

Chilblain lupus erythematosus is a rare, cold-induced form of chronic cutaneous lupus that can occur in both genetic and sporadic forms. It is characterized by acral skin lesions and is commonly associated with autoimmunity and type I interferon pathway activation. Diagnosis is based on clinical features and histological findings. While topical and systemic therapies can be effective, the disease is often chronic and relapsing. We describe a case of a 48-year-old woman with chilblain lupus erythematosus who achieved almost complete clinical remission following treatment with hydroxychloroquine and methotrexate.

The adaptor molecule STING is embedded in the endoplasmic reticulum (ER) membrane. In innate immunity, STING is a critical cascade in regulating the cytoplasmic DNA-recognizing signaling. Aberrant STING signaling facilitates the host body to secrete an intolerable level of inflammatory cytokines as well as interferons, causing interferonopathies including STING-associated infantile vasculopathy, familial chilblain lupus, and amyotrophic lateral sclerosis. Suppressing the disordered STING signaling has demonstrated to ameliorate the inflammatory impairments of interferonopathy diseases. In this article, we provide the discovery of thieno[2,3-b][1,4]thiazin-2(3H)-one STING inhibitors. Through the structure-activity relationship (SAR) exploration, we identified compound 11 h as an oral-available STING inhibitor possessing cellular mouse- or human-STING inhibiting IC50 of 8.8 or 11.5 nM. Compound 11 h markedly hindered the cellular STING cascade in both murine- and human-derived cells. Furthermore, 11 h achieved robust in vivo activity opposing MAS-2-caused systemic inflammatory damage and cisplatin-caused renal inflammation and injury. Proposed binding model of 11 h-STING indicates that 11 h engages the transmembrane area of STING.

Autosomal recessive Aicardi-Goutières syndrome (AGS) and autosomal dominant familial chilblain lupus (FCL) are rare type I interferonopathies that can both result from loss-of-function variants in the TREX1 gene, which encodes a DNA exonuclease. Although phenotypic variability is well recognized in TREX1-related disorders, intrafamilial phenotypic discordance is seldom seen. We describe two siblings carrying a novel homozygous TREX1 variant (c.341G > T, p.Arg114Leu) who exhibit strikingly different clinical phenotypes. The younger sibling presented at 4 months of age with features of AGS, including tetraspasticity, muscular hypotonia and global developmental delay. Brain MRI showed brain atrophy and white matter abnormalities. In contrast, his older brother developed cutaneous chilblain lesions during the cold season at age 3 but was otherwise normally developed. Despite these divergent clinical presentations, both children demonstrated a highly elevated interferon signature. This case report expands the genetic and clinical spectrum of TREX1-related disorders and illustrates the considerable phenotypic variability associated with biallelic TREX1 variants in AGS. It highlights the complexity of genotype-phenotype correlations in type I interferonopathies and underscores the need for further research into factors that modulate disease expression.