Uncommon toxic epidermal necrolysis -like presentation of cutaneous lupus erythematosus: A series of 6 cases.

TEN like Lupus erythematosus is an uncommon life-threatening variant of Lupus erythematosus. It is usually associated with flares of systemic lupus erythematosus and also because of widespread skin erosions, it can cause acute skin failure. It is often confused with drug induced TEN, however the management of both the diseases is different and hence correct diagnosis becomes crucial. In this study we aimed to assess the clinical characteristics and outcome of TEN like LE in the Indian population. All patients satisfying ACR/EULAR 2019 criteria for SLE and clinically diagnosed with TEN like LE were retrospectively reviewed. A total of 6 patients were identified. All patients were female. Except 1 patient who presented de-novo, the others had pre-existing symptoms of connective tissue disease. Half of the patients had palmoplantar involvement. Mucosal involvement was only mild. Majority had systemic involvement in the form of nephritis followed by arthralgia, autoimmune hepatitis and autoimmune hemolytic anemia.

Comparison of patients with isolated cutaneous lupus erythematosus versus systemic lupus erythematosus with cutaneous lupus erythematosus as the sole clinical feature: A monocentric study of 149 patients.

BACKGROUND: Cutaneous lupus erythematosus (CLE) may present as an isolated entity or be classified as Systemic lupus erythematosus (SLE) by the presence of laboratory abnormalities, including cytopenia, low complement levels, and/or autoantibodies (CLE with laboratory SLE). OBJECTIVE: To compare isolated CLE and CLE with laboratory SLE and to validate an existing 3-item score with age < 25 years (1 point), phototypes V to VI (1 point), antinuclear antibodies ≥ 1:320 (5 points) to predict the risk of progression from CLE to severe SLE (sSLE). METHODS: Monocentric cohort study including consecutive patients with CLE. CLE with laboratory SLE was defined by 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for SLE score of ≥10 points at baseline with CLE as the sole clinical feature. RESULTS: Of the 149 patients with CLE, 20 had CLE with laboratory SLE. The median follow-up duration was 11.3 years (IQR: 5.1-20.5). Ten patients (7%) had sSLE developed. In survival analysis, the risk of progression to sSLE was higher among CLE with laboratory SLE (hazard ratio = 6.69; 95% CI: 1.93-23.14, P < .001) compared to isolated CLE. In both groups, none of the patients with a risk score ≤ 2 had sSLE developed. LIMITATIONS: Monocentric study with a limited number of patients. CONCLUSIONS: CLE with laboratory patients with SLE have a higher risk of progression to sSLE than isolated CLE.

Blaschkoid melanotic cutaneous lupus erythematosus with "melanocytic nests".

Melanotic cutaneous lupus erythematosus (LE) is a newly described clinical variant of chronic cutaneous LE, presenting with localized or diffuse brownish or grayish macular and reticulated pigmentation in the absence of erythema, scaling, atrophy, scarring, or telangiectasia. The diagnosis is based upon histopathology, which demonstrates the characteristic features of LE with an interface vacuolar dermatitis with melanophages, and a superficial and deep, perivascular and periadnexal lymphocytic infiltrate with mucin deposition. Herein, we describe a case of a 61-year-old White male presenting with melanotic cutaneous LE with a blaschkoid distribution on his face in which the histopathological phenomenon of "true melanocytic nests" in the setting of a lichenoid pattern was seen. We want to highlight how nests of cellular aggregates at the dermoepidermal junction labeling with melanocytic markers may occur in the setting of an interface tissue reaction. This benign reactional pattern may mimic atypical melanocytic proliferations, especially on sun-damaged skin. Clinicopathological correlation and careful microscopic examination using a panel of multiple melanocytic markers is crucial for making an accurate final diagnosis. All the cases of melanotic cutaneous LE reported in the literature are also reviewed.

Line-field confocal optical coherence tomography: Characteristic hints for the diagnosis of scarring alopecia due to lupus erythematodes: A preliminary study.

INTRODUCTION: Lupus erythematosus (LE) is an inflammatory autoimmune disease, that can affect the skin to varying degree. In particular, discoid LE (DLE) and the rare form of lupus panniculitis/profundus are associated with scarring alopecia. The heterogeneity of the clinical, dermatoscopic, and histologic presentation poses a major challenge to the clinician in the diagnosis and differential diagnosis of other forms of scarring alopecia. OBJECTIVE: While noninvasive imaging techniques using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) have proven to be helpful in the diagnosis of scarring alopecia in the context of LE, this study aimed to investigate line-field confocal OCT (LC-OCT) to identify characteristic features of cicatricial alopecia in LE. METHODS: Fifteen patients with cicatricial alopecia in LE were included and the most affected/inflamed areas of the scalp were prospectively examined. In analogy to histopathology and previously reported criteria in RCM, all images were evaluated according to seven established criteria and underwent descriptive analyses. RESULTS: LC-OCT revealed characteristic features of cicatricial alopecia, such as lymphocytic interface dermatitis (14/15; 93.3%) and basal cell vacuolization (13/15; 86.7%). The most impressive feature was the occurrence of prominent hyperreflective fibers in 14/15 patients (93.3%). CONCLUSION: LC-OCT imaging can noninvasively detect morphologic criteria such as lymphocytic and vacuolar interface dermatitis of cicatricial alopecia due to LE. In particular, the presence of hyperreflective collagen fibers appears to be a characteristic easily recognizable feature that may facilitate differential diagnosis with other forms of cicatricial alopecia. Further studies are mandatory to differentiate other forms of scarring alopecia.

Histopathologic Overlap Between Bullous Lupus Erythematosus and Linear IgA Bullous Dermatosis: A Comparative Study.

ABSTRACT: Bullous lupus erythematosus (BLE) and linear IgA disease (LAD) are rare autoimmune subepidermal blistering diseases, with overlapping features despite different pathogenetic mechanisms. Diagnosis is based on immunofluorescence and serology. This retrospective study was undertaken to compare the histopathologic features of BLE and LAD (11 cases each). The mean age was 36 years in both groups, and female preponderance was noted in BLE. Clinically, all cases presented as tense, itchy blisters distributed over the trunk, face, and extremities. Subepidermal neutrophil-rich blisters were seen in 60% BLE and 54.54% LAD cases. Eosinophils in the blisters were noted in 4 cases (36.4%) of linear IgA bullous dermatosis, but not in any of the BLE cases. The adjacent epidermal changes noted include spongiosis (33%; 40%), papillary microabscesses (22%; 20%), and basal tagging by neutrophils (77%; 70%). Superficial perivascular inflammation was seen in all cases while deep perivascular inflammation was observed in 54% BLE and 36% LAD cases. Lymphocytes were the predominant infiltrate. Increased dermal mucin was seen in 60% BLE and 45% LAD cases. None of the histopathologic features showed a statistically significant difference between the 2 groups. Hence, histopathology alone is of limited value in distinguishing the 2 groups. Diagnosis rests on immunofluorescence and serologic findings, which should be used even in cases that seem to be classic LAD or patients without history of systemic lupus erythematosus.

Diffuse Cutaneous Mastocytosis: A Current Understanding of a Rare Disease.

Mastocytosis is a heterogeneous disease characterized by the expansion and accumulation of neoplastic mast cells in various tissues. Diffuse cutaneous mastocytosis (DCM) is a rare and most severe form of cutaneous mastocytosis, which typically occurs in childhood. There have been reports of a familial DCM with specific gene mutations, indicating both sporadic and hereditary factors involved in its pathogenesis. DCM is associated with severe MC mediator-related symptoms and an increased risk of anaphylaxis. The diagnosis is based on the appearance of skin lesions, which typically show generalized thickening, erythroderma, blistering dermographism, and a positive Darier's sign. Recognition, particularly in infants, is challenging due to DCMs resemblance to other bullous skin disorders. Therefore, in unclear cases, a skin biopsy is crucial. Treatment focuses on symptom management, mainly including antihistamines and mast cell stabilizers. In extremely severe cases, systemic steroids, tyrosine kinase inhibitors, phototherapy, or omalizumab may be considered. Patients should be equipped with an adrenaline autoinjector. Herein, we conducted a comprehensive review of literature data on DCM since 1962, which could help to better understand both the management and prognosis of DCM, which depends on the severity of skin lesions, intensity of mediator-related symptoms, presence of anaphylaxis, and treatment response.

Neonatal lupus erythematosus presenting as a non-bullous histiocytoid neutrophilic dermatosis.

Histopathologic findings in neonatal lupus erythematosus (NLE) are usually congruent with those of subacute cutaneous lupus erythematosus. However, neutrophilic dermatosis-type histopathologic features are being increasingly recognized in the literature including rare cases with variant histiocytoid morphology. We report the case of a 7-week-old male presenting with figurate erythema. His mother was found to have elevated anti-nuclear antibodies and was positive for anti-SSA/Ro, anti-SSB/La antibodies and Ro52 autoantibodies. The infant had a similar serological profile. Skin biopsy showed a histiocytoid interstitial infiltrate with mild lichenoid features, sparse neutrophils and mild leukocytoclasis. The histiocytoid infiltrate showed prominent CD68, CD163, and myeloperoxidase expression. Isolated clusters of CD123+ histiocytes were also present. This case highlights the rare finding of non-bullous neutrophilic dermatosis with histiocytoid change in neonatal lupus. In neonates presenting with figurate erythemas with morphological histiocytic change on biopsy, NLE should be considered as a differential diagnosis and investigated for accordingly.

A case of reactive granulomatous dermatitis associated with neonatal lupus erythematosus.

Neonatal lupus erythematosus (NLE) is an uncommon disorder affecting approximately one out of 20 000 live births in the United States. Common manifestations of NLE include cutaneous eruptions and cardiac involvement. The typical rash of NLE most closely resembles the rash of subacute cutaneous lupus erythematosus both clinically and histopathologically. We present a case of reactive granulomatous dermatitis (RGD) associated with NLE in a 3-month-old male in whom the initial histopathology and immunohistochemistry were concerning for hematologic malignancy. RGD is a unifying term used to describe cutaneous granulomatous eruptions that occur in response to a variety of stimuli, including autoimmune connective tissue diseases. Our case demonstrates the range of histopathological findings that may be present in the setting of NLE.

German Shorthaired Pointer dogs with exfoliative cutaneous lupus erythematosus develop immune-complex membranous glomerulonephropathy.

German Shorthaired Pointer (GSHP) dogs with a UNC93B1 gene mutation develop exfoliative cutaneous lupus erythematosus (ECLE) and kidney disease resembling lupus nephritis in humans. The objective of this study was to characterize the kidney disease by light microscopy, immunofluorescence, and electron microscopy in a population of GSHP dogs with ECLE. Medical records were reviewed, and light microscopy of kidneys from 7 GSHP dogs with a previous histologic diagnosis of ECLE was performed. Immunofluorescence of fresh-frozen kidney from 1 dog and transmission electron microscopy of kidney from that dog and 2 additional dogs were performed. Five of 7 dogs had proteinuria diagnosed by urinalysis or urine protein-to-creatinine ratio. Two of 7 dogs were intermittently hypoalbuminemic, and none were azotemic. Histologic findings included early (2 dogs) to late (5 dogs) membranous glomerulonephropathy characterized by mild-to-severe glomerular capillary loop thickening and tubular proteinosis. In all 7 cases, trichrome staining revealed red granular immune deposits on the subepithelial surface of the glomerular basement membrane. Immunofluorescence revealed strong granular labeling for immunoglobulins and complement protein C3. Electron microscopy demonstrated subepithelial electron-dense immune deposits encircled by the remodeled glomerular basement membrane. These findings are diagnostic of immune-complex membranous glomerulonephropathy and are similar to class V lupus in humans. This cohort of GSHP dogs with ECLE developed immune-complex membranous glomerulonephropathy, which we hypothesize is a manifestation of systemic lupus erythematosus. GSHP dogs with ECLE should undergo clinical evaluation of renal function for early identification and treatment.

Subacute cutaneous lupus erythematosus following ribociclib therapy for metastatic breast cancer.

INTRODUCTION: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with drugs with different mechanisms of action, including anti-hypertensives, tumour necrosis factor-α inhibitors and even some chemotherapy medicines. In the last years, a few reports have been described in patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib. CASE REPORT: Here, we describe a case of DI-SCLE in association with ribociclib and exemestane in a woman diagnosed with metastatic breast cancer. MANAGEMENT AND OUTCOME: Topical mometasone was prescribed for two weeks with complete resolution of lesions, also abemaciclib was substituted for ribociclib, and the patient had stable disease with no relapse of DI-SCLE. DISCUSSION: To our knowledge, this is the first report of ribociclib-induced SCLE but based on the DI-SCLE reported cases associated others CDK4/6 inhibitors, the role of this family of drugs in dermatopathology must be further investigated.

Mucocutaneous diseases with manifestations in the head and neck region: 24 years of experience in a Dermatology service.

BACKGROUND: This study aimed to evaluate the clinicopathological features of mucocutaneous diseases with manifestation in the head and neck region. MATERIAL AND METHODS: A retrospective analysis of a dermatology reference center database was carried out. Over 24 years. Clinicopathological data were collected from medical records and the data was analyzed by descriptive statistics. RESULTS: A total of 11.538 medical records were analyzed, being 152 cases of mucocutaneous diseases with manifestations in the head and neck region. Cutaneous lupus erythematosus was the most prevalent diagnosis (66.4%). Face (44.1%), females (79.6%), and patients with 45 years mean age were the most common features. In the oral cavity, the most affected region was the buccal mucosa (37.5%). CONCLUSIONS: Mucocutaneous diseases with head and neck manifestation were rare in the sample analyzed (1.3%), with cutaneous lupus erythematosus and lichen planus being the most common lesions in this region.

Cutaneous erythematous lupus with acneiform presentation.

We present a 57-year-old woman with cutaneous lupus erythematosus (CLE), initially treated as acne. She noted blemishes, including nodules and facial swelling for nine months associated with discrete itching of the ears. Examination showed multiple malar nodules, comedones, pustules, atrophic scars, and hyperpigmentation. A biopsy was performed and revealed atrophic epidermis, discrete hyperkeratosis, vacuolar degeneration of basal layer, basal membrane zone with upper dermal lymphohistiocytic inflammatory infiltrate and deep perivascular and peri-adenexal lymphocytes, vascular ectasia, and mucin deposits. The acneiform presentation of CLE is commonly underdiagnosed due to the similarity with inflammatory acne. Histopathologic diagnostic in acneiform lupus is of extreme importance. This case emphasizes the relevance of knowing the notable variety of presentations of CLE and considering this diagnosis.

Lupus erythematosus-specific bullous lesions.

Lupus erythematosus (LE)-specific bullous lesions are often difficult to distinguish from other bullous diseases presenting in patients with systemic lupus erythematosus. Herein, we describe a 49-year-old woman with systemic lupus erythematosus with recurrent tense bullae on the forearms. Clinical, histopathologic, and serologic findings led to the diagnosis of LE-specific bullous lesions. We also summarize the diagnostic clues for distinguishing LE-specific bullous lesions, bullous systemic lupus erythematosus, and erythema multiforme-like lesions in LE (Rowell syndrome).

Non-scarring alopecia of lupus erythematosus: A comprehensive review.

BACKGROUND: Although non-scarring alopecia (NSA) is a frequent clinical finding in patients with systemic lupus erythematosus (SLE), it has been poorly described in the literature. It is considered a nonspecific sign in the current classification of skin lesions of LE. The aim of this study was to give an updated overview of the spectrum of NSA in LE patients, with emphasis on the clinical significance thereof. METHOD: We conducted a review of the English literature using the PubMed-Medline database using the keywords "Alopecia" + "Lupus erythematosus". Publications describing LE patients with NSA were included. RESULTS: Data for 237 patients from 27 publications were analyzed. Ninety-one patients had diffuse NSA, 43 had patchy NSA, 83 had lupus hair, 3 had alopecia of dermal cutaneous LE, and 17 had alopecia of linear and annular lupus panniculitis of the scalp. Patients with diffuse/patchy NSA and lupus hair shared the following features: strong association with systemic activity of LE, subtle clinical/trichoscopic signs of inflammation, histological aspect consistent with lesions specific to cutaneous LE, high likelihood of response to SLE therapy, and absence of progression to scarring alopecia. Association with SLE was rare in patients with dermal cutaneous LE or linear and annular lupus panniculitis of the scalp, and skin-directed therapies were most often effective. One patient of each subtype progressed to scarring alopecia. DISCUSSION: Diffuse/patchy NSA and lupus hair may represent a topographic variation of a single entity specific for LE. Prospective studies are warranted to further document the clinical significance of this manifestation.

Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus.

Background and Objectives: Cutaneous lupus erythematosus (CLE) presents clinically heterogeneous manifestations, partially explained by the different expression of Toll-like receptors (TLRs) type 8 and 9, located to endosomal compartments where they are poised to recognize microbial nucleic acids. This disease is empirically treated with hydroxychloroquine (HCQ), which is hallmarked with a safe and effective profile, but induces a slow and sometimes clinically insufficient therapeutic response. Currently, no biomarkers predictive of response are validated or even proposed in the scientific literature. We aimed to evaluate endosomal TLR type 7, 8 and 9 as predictive biomarkers of HCQ efficacy. Materials and Methods: We conducted a case-control study comparing CLE patients retrospectively assigned to three subgroups based on 3-6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = <40% vs. II = 40-80% vs. III = >80%). Before HCQ, lesional skin specimens were collected in untreated CLE and through immunohistochemistry; TLR-7, -8 and -9 expression was evaluated in the epidermis and the lymphocytic infiltrate was evaluated in the dermis. Results: Sixty-six lesional skin biopsies were compared with healthy controls. CLE patients displayed lower epidermal expression of total TLR 8 and 9 as well as infiltrating TLR-8, TLR9 + lymphocytes compared to controls. High HCQ responders differed from low responders for TLR-9 positivity (high vs. low) and for the lymphocytic dermal infiltrate (high vs. low). Conclusions: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients.

Skin CD4+ Trm cells distinguish acute cutaneous lupus erythematosus from localized discoid lupus erythematosus/subacute cutaneous lupus erythematosus and other skin diseases.

BACKGROUND: Although the contribution of aberrant CD4+ T cell signaling to systemic lupus erythematosus (SLE) is well established, its role in cutaneous lupus erythematosus (CLE) skin is largely unknown. Because the rate of systemic manifestations varies in each subtype, resident memory CD4+ T cells in lesions that are responsible for only skin-associated tissue responses may vary in each subtype. However, the role of CD4+ tissue-resident memory T (CD4+ Trm) cells in each CLE subtype remains unclear. OBJECTIVES: To analyze and compare CD4+ Trm cells and absent in melanoma 2 (AIM2) identified by smart RNA sequencing (Smart-seq) in CD4+ Trm cells from patients with acute CLE (ACLE), subacute CLE (SCLE), and localized discoid lupus erythematosus (localized DLE) lesions. METHODS: We performed Smart-seq to investigate differences in dermal CD4+ Trm cells between patients with ACLE and normal controls (NCs). Multicolor immunohistochemistry was utilized to measure the levels of AIM2 in CD4+ Trm cells present in the skin of 134 clinical patients, which included patients with localized DLE (n = 19), ACLE (n = 19), SCLE (n = 16), psoriasis (n = 12), rosacea (n = 17), lichen planus (n = 18), and annular granuloma (n = 15), as well as NCs (n = 18). RESULTS: The Smart-seq data showed higher AIM2 expression in skin CD4+ Trm cells from ACLE lesions than NCs (fold change >10, adjusted P < 0.05). AIM2 expression in CD4+ Trm cells did not vary according to age or sex. AIM2 expression in CD4+ Trm cells was significantly lower in patients with ACLE (6.38 ± 5.22) than localized DLE (179.41 ± 160.98, P < 0.0001) and SCLE (63.43 ± 62.27, P < 0.05). In an overall comparison of ACLE with localized DLE and SCLE, the receiver operating characteristic curve for AIM2 expression in CD4+ Trm cells had a sensitivity of 100.00% and a specificity of 82.86% at a cutoff value of 18.26. In a comparison of ACLE with localized DLE, the sensitivity was 89.47%, and the specificity was 100.00% at a cutoff value of 12.26. In a comparison of ACLE with SCLE, the sensitivity was 100.00%, and the specificity was 75.00% at a cutoff value of 18.26. CONCLUSIONS: The number of CD4+ Trm cells is increased in lesions of SCLE and localized DLE compared to ACLE, suggesting that CD4+ Trm cells may have a more crucial role in persistent lesions of SCLE and localized DLE. In addition, AIM2 expression in CD4+ Trm cells discriminates patients with ACLE from those with localized DLE and SCLE.

Chilblains in immune-mediated inflammatory diseases: a review.

Chilblains were first described over a hundred years ago as cutaneous inflammatory lesions, typically on the digits, occurring on cold exposure. Chilblains can be primary, or secondary to a number of conditions such as infections, including COVID-19, and immune-mediated inflammatory disorders (IMIDs) with SLE being the commonest. Chilblain lupus erythematosus (CHLE) was first described in 1888 as cold-induced erythematous lesions before the terms 'chilblains' or 'perniosis' were coined. Diagnostic criteria exist for both chilblains and CHLE. Histopathologically, CHLE lesions show interface dermatitis with perivascular lymphocytic infiltrate. Immunofluorescence demonstrates linear deposits of immunoglobulins and complement in the dermo-epidermal junction. This narrative review focuses on chilblains secondary to immune-mediated inflammatory disorders, primarily the epidemiology, pathogenesis and treatment of CHLE.

Cutaneous manifestations of lupus erythematosus: a practical clinicopathological review for pathologists.

Accurate diagnosis of connective tissue diseases is often challenging, and relies upon careful correlation between clinical and histopathological features, direct immunofluorescence studies and laboratory work-up. Lupus erythematosus (LE) is a prototype of connective tissue disease with a variety of cutaneous and systemic manifestations. Microscopically, cutaneous LE is classically characterised by an interface dermatitis although other histopathological patterns also exist, depending upon the clinical presentation, location and chronicity of the skin lesions. In this article, we review the clinical, serological, histopathological and direct immunofluorescence findings in LE-specific and LE non-specific skin lesions, with an emphasis upon lesser-known variants, newly described features and helpful ancillary studies. This review will guide general pathologists and dermatopathologists in accurately diagnosing and subclassifying cutaneous LE.

Tight correlation of 5-hydroxymethylcytosine expression with the scarring damage of discoid lupus erythematosus.

OBJECTIVE: Cutaneous lupus erythematosus (CLE) is a heterogenous skin disease. The two most common subtypes are discoid LE (DLE) characterized by scarring skin damage and acute CLE (ACLE) presenting with transiently reversible skin lesions. It remains unknown what causes the difference of skin lesions. Studies have shown the existence of tissue-specific 5-Hydroxymethylcytosine (5 hmC)-modified regions in human tissues, which may affect the tissue-related diseases. Here, we aim to assess the expression of 5 hmc in DLE and ACLE lesions and explore the relationship of 5 hmc with scarring damage in DLE. METHODS: 84 CLE samples were included in the study. We evaluated the skin damage score and reviewed the histopathologic sections. Immunohistochemical staining was performed to detect the expression of 5 hmc in the appendage and periappendageal inflammatory cells. The 5 hmc expression in periappendageal lymphocytic cells was investigated by multi-spectrum immunohistochemistry staining. RESULTS: Scarring/atrophy was the most significant damage in differentiating the DLE from ACLE. Perifollicular inflammatory infiltration was present in all patients with DLE scarring alopecia (DLESA). The 5 hmc expression in the appendage and periappendageal inflammatory cells was significantxly increased in DLESA than ACLE. Similar expression pattern was seen in the staining of IFN-alpha/beta Receptor (IFNAR). The expression of 5 hmc in the appendage was positively correlated with that in the periappendageal inflammatory cells. There was an increased 5 hmc expression in lymphocytes cluster around hair follicle consisting of CD4+ cells, CD8+ cells, and CD19+ cells in DLESA lesions. CONCLUSION: These data demonstrate a close association of the expression pattern of 5 hmc with the histopathological characteristic distribution, and with the type I interferons (IFNs) signals in DLESA, supporting the importance of 5 hmc in the amplification of appendage damage and periappendageal inflammation, thereby offering a novel insight into the scarring damage of DLE and the heterogeneity of CLE skin lesions.

The Overlap between Genetic Susceptibility to COVID-19 and Skin Diseases.

Coronavirus disease 2019 (COVID-19) mainly affects the respiratory system, but the involvement of other organ systems has also been commonly reported. Acute acro-ischemia or chilblain like lesions were among the first recognized dermatological presentations of COVID-19. Though the occurrence of such lesions has been attributed to the similar interferon-1 mediated immune response in both COVID-19 and systemic lupus erythematosus, we propose another possible explanation based on a common genetic background. In a recent genome-wide association study, the 3p21.31 region was found to be associated with COVID-19 severity. This region also contains the TREX1 gene. Missense mutations of the TREX1 gene are responsible for familial chilblain lupus and its genetic polymorphisms have been implicated in the pathogenesis of systemic lupus erythematosus. Based on this observation, herein we have reviewed other COVID-19 risk loci for potential overlap with dermatological conditions.