Population Characteristics, Symptoms, and Risk Factors of Idiopathic Chilblains: A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: Chilblains/perniosis is a non-freezing cold injury causing painful inflammatory skin lesions. Its pathogenesis remains poorly understood because it is often studied as secondary to other underlying conditions. METHODS: We systematically investigated the population characteristics, symptoms, and predisposing factors of chilblains in healthy adults exposed to cool/cold environments. We screened PubMed, Embase, and Cochrane Library, and we adopted PRISMA reporting guidelines (PROSPERO: CRD42021245307). The risk of bias was assessed by two independent reviewers (RTI item bank). Random-effects model meta-analyses were performed to calculate the pooled prevalence of histopathological features. Mixed-effects meta-regressions were used to assess other sources of between-study heterogeneity. RESULTS: Thirteen studies (477 patients) were included. Chilblains affect more women than men, up to 12% of the body skin surface, and most frequently, the hands and fingers. Meta-analyses of nine studies (303 patients) showed a frequent presence of perivascular lymphocytic infiltrate (81%), basal epidermal-cell layer vacuolation (67%), papillary dermal edema (66%), and perieccrine lymphocytic infiltrate (57%). Meta-regressions (p ≤ 0.05) showed that smoking and frequent occupational exposure to water increase the likelihood of histopathological features. CONCLUSIONS: The population characteristics, symptoms, and predisposing factors of chilblains revealed in this analysis should be incorporated in medical care to improve the condition's diagnosis and management.

COVID-19 Toes and Other Skin Lesions During the Pandemic: Emerging Entities?

There is accumulating evidence to indicate an association between coronavirus infectious disease 2019 (COVID-19) and clusters of incident cutaneous eruptions. Of these, chilblains-like perniosis have received widespread medical and media attention. These typically affect the toes, and have been called "COVID-toes." Other acral lesions such as large bullae have also been reported. However, a definitive causal relationship with the severe acute respiratory syndrome coronavirus 2 has not yet been definitively proven, nor has a pathogenic mechanism been established. These episodes are self-limiting, but we need to know whether long-term sequelae exist.

Chilblains during lockdown are associated with household exposure to SARS-CoV-2: a multicentre case-control study.

OBJECTIVES: During the COVID-19 pandemic, numerous cases of chilblains have been reported. However, in most cases, RT-PCR or serology did not confirm SARS-CoV-2 infection. Hypotheses have been raised about an interferon-mediated immunological response to SARS-CoV-2, leading to effective clearance of the SARS-CoV-2 without the involvement of humoral immunity. Our objective was to explore the association between chilblains and exposure to SARS-CoV-2. METHODS: In this multicentre case-control study, cases were the 102 individuals referred to five referral hospitals for chilblains occurring during the first lockdown (March to May 2020). Controls were recruited from healthy volunteers' files held by the same hospitals. All members of their households were included, resulting in 77 case households (262 individuals) and 74 control households (230 individuals). Household exposure to SARS-CoV-2 during the first lockdown was categorized as high, intermediate or low, using a pre-established algorithm based on individual data on symptoms, high-risk contacts, activities outside the home and RT-PCR testing. Participants were offered a SARS-CoV-2 serological test. RESULTS: After adjustment for age, the association between chilblains and viral exposure was estimated at OR 3.3, 95% CI (1.4-7.3) for an intermediate household exposure, and 6.9 (2.5-19.5) for a high household exposure to SARS-CoV-2. Out of 57 case households tested, six (11%) had positive serology for SARS-CoV-2, whereas all control households tested (n = 50) were seronegative (p = 0.03). The effect of potential misclassification on exposure has been assessed in a bias analysis. DISCUSSION: This case-control study demonstrates the association between chilblains occurring during the lockdown and household exposure to SARS-CoV-2.

Acrofacial necrotic ulcers in an infant: An undiagnosed presentation.

Acral necrotic ulcers in infancy are rare but have been described in type I interferonopathies. Herein, we present a case of an 8-year-old child who presented at the age of one month with severe ulceronecrotic lesions on the face and limbs with exacerbations following exposure to cold weather. Despite extensive investigation the case remains undiagnosed to this day. We hypothesize that this case represents a novel and yet unknown autoinflammatory disease.

COVID-19 Pediatric Dermatology.

Children are a unique subset of patients in relation to the COVID-19 pandemic, often presenting asymptomatically, mildly, or atypically. Manifestations of the skin may be a primary (or the only) presenting sign. Recognizing cutaneous manifestations of COVID-19 in the pediatric population is important to guiding precautions, testing, and management for patients and close contacts. Whereas some dermatologic signs in children overlap with those in adults, other skin findings are reported with higher frequency in children and may be clues to multisystemic sequelae. This article describes presentation, pathophysiologic theories, and management strategies for cutaneous manifestations of COVID-19 in children.

Lesiones cutáneas en niños durante la primera ola de la pandemia por SARS-CoV-2 / Skin lesions in children during the first wave of the SARS-CoV-2 pandemic

Introducción: Las manifestaciones cutáneas se han incluido en el espectro clínico de los pacientes con COVID-19. Nuestro objetivo fue determinar la asociación entre las lesiones cutáneas observadas en niños durante la primera ola de la pandemia y la infección por SARS-CoV-2, analizando otras posibles etiologías infecciosas o autoinmunes.Material y métodosEstudio observacional, multicéntrico, de corte transversal, desarrollado en niños con manifestaciones cutáneas desde abril hasta mayo de 2020. La determinación de SARS-CoV-2 se realizó mediante PCR en exudado nasofaríngeo y/o serología.ResultadosSe seleccionó a 62 niños; 9 (14,5%) presentaron serología positiva para SARS-CoV-2, siendo la PCR negativa en todos los casos en los que se realizó. Los pacientes con serología positiva para SARS-CoV-2 presentaron con más frecuencia lesiones pernióticas y/o vesiculosas (66,7 vs. 24,5%; p=0,019). El exantema generalizado, urticarial y maculopapuloso fue más habitual en el grupo de pacientes con serología negativa (37,7 vs. 0%; p=0,047); se aislaron otros patógenos en el 41,5%. No hubo diferencias significativas en cuanto a la positividad de autoanticuerpos entre ambos grupos.ConclusiónEn nuestro estudio, las lesiones de tipo perniosis o vesiculosas se relacionaron significativamente con el contacto previo con SARS-CoV-2. (AU)

Background: Cutaneous manifestations have been included in COVID-19 patients’ clinical spectrum. Our objective was to determine the association between skin lesions in children and SARS-CoV-2 infection, analyzing others possible infectious/autoimmune etiologies.Material and methodsObservational, multicenter, cross-sectional study, about children with skin manifestations from April to May 2020. The diagnosis of SARS-CoV-2 was performed by PCR in nasopharyngeal exudate and/or presence of antibodies by serology.ResultsSixty-two children were included, 9 (14.5%) presented positive antibodies to SARS-CoV-2, with no positive PCR to SARS-Cov-2 in those patients in whom it was made. Patients with positive serology to SARS-CoV-2 presented chilblains and/or vesicular-bullous skin lesions more frequently (66.7% vs. 24.5%, p=0.019). Generalized, urticarial and maculopapular rash was more common in patients with negative antibodies (37.7 vs. 0%, p=0.047), others pathogens were isolated in 41.5% of these patients. There were no significant differences in the positivity for autoantibodies between both groups.ConclusionIn our study, the presence of chilblains-like and/or vesicular lesions were significantly related to SARS-CoV-2 previous contact. (AU)

[Skin lesions in children during the first wave of the SARS-CoV-2 pandemic]. / Lesiones cutáneas en niños durante la primera ola de la pandemia por SARS-CoV-2.

BACKGROUND: Cutaneous manifestations have been included in COVID-19 patients' clinical spectrum. Our objective was to determine the association between skin lesions in children and SARS-CoV-2 infection, analyzing others possible infectious/autoimmune etiologies. MATERIAL AND METHODS: Observational, multicenter, cross-sectional study, about children with skin manifestations from April to May 2020. The diagnosis of SARS-CoV-2 was performed by PCR in nasopharyngeal exudate and/or presence of antibodies by serology. RESULTS: Sixty-two children were included, 9 (14.5%) presented positive antibodies to SARS-CoV-2, with no positive PCR to SARS-Cov-2 in those patients in whom it was made. Patients with positive serology to SARS-CoV-2 presented chilblains and/or vesicular-bullous skin lesions more frequently (66.7% vs. 24.5%, p=0.019). Generalized, urticarial and maculopapular rash was more common in patients with negative antibodies (37.7 vs. 0%, p=0.047), others pathogens were isolated in 41.5% of these patients. There were no significant differences in the positivity for autoantibodies between both groups. CONCLUSION: In our study, the presence of chilblains-like and/or vesicular lesions were significantly related to SARS-CoV-2 previous contact.

Idiopathic perniosis presenting as acral purpuric lesions: Clustering of cases before COVID-19 pandemic and their comparison with chilblain like lesions reported in the literature.

Perniosis/chilblains are the acral inflammatory skin lesions developing in susceptible individuals as an abnormal reaction to cold. In the absence of a discernible cause, it is labeled as idiopathic perniosis (IP). With the ongoing COVID-19 pandemic, there was an upsurge of reports of chilblain like lesions (CLL) especially in young patients possibly implicated to the SARS-CoV-2 virus. Twelve clinically suspected and histopathologically confirmed cases of IP seen from November 2019 through February 2020 were retrospectively recruited. Clinical, dermoscopic, and histopathological characteristics of these were reviewed and compared with CLL reported in the literature. Mean age of patients was 26.58 ± 15.18 years with an equal male to female ratio. Characteristic histopathology findings were spongiosis (100%), dermal edema (100%), perivascular lymphocytic infiltrate (100%) with peri-eccrine accentuation (66.7%), keratinocyte necrosis (50%), focal basal vacuolar damage (58.3%), and lymphocytic vasculitis (58.3%). Significant dermoscopy findings were variable background color ranging from dull red and violaceous to copper red and brown orange, coiled vessels (44.4%) and orange-red structureless areas (63.9%). Lesions over palms and soles preferentially had white dots/clods and lines (38.9%). There appears no exclusive histopathological as well as dermoscopy features of CLL and IP, yet certain clues can be appreciated. Keratinocyte necrosis and severe dermal edema favors IP, whereas fibrin thrombi with involvement of both superficial and deep dermal vessels favor CLL. Dermoscopically presence of irregular, linear or branching vessels, red/purple dots and clods and gray brown reticule supports CLL while white dots/clods and lines supports IP.

Actividad lúpica en paciente con enfermedad renal terminal: reporte de caso / Lupus activity in a patient with end-stage renal disease: a case report

RESUMEN El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que afecta múltiples órganos; el compromiso renal se encuentra en el 50% de los pacientes y es variable de acuerdo con el grupo racial y étnico. Se estima que el 10% de los pacientes con nefritis lúpica (NL) desarrollan enfermedad renal terminal (ERT) y, una vez que se da la progresión, el 80% de los pacientes negativizan los marcadores de actividad. Sin embargo, aunque es inusual, la reactivación de la enfermedad puede presentarse en compromiso renal avanzado y es importante diagnosticarla oportunamente para definir la causa, tratarla y evitar complicaciones. Presentamos el caso clínico de una paciente de 45 arios, con ERT en diálisis peritoneal, que se encontraba en remisión de la enfermedad y posteriormente desarrolló actividad lúpica.

ABSTRACT Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs, and renal involvement is found in 50% of patients and is variable according to racial and ethnic group. It is estimated that 10% of patients with lupus nephritis (NL) develop end-stage renal disease (ERT), and once progression occurs, 80% of patients are negative for activity markers. However, although it is rare, the reactivation of the disease can occur in advanced renal involvement, and it is important to diagnose it in a timely manner to define the cause and treat it, avoiding complications.

Approach to Chilblains During the COVID-19 Pandemic [Formula: see text].

Coronavirus disease (COVID-19) chilblains is a well-reported cutaneous pattern of severe acute respiratory syndrome coronavirus (SARS-CoV-2). Through this narrative review, we provide an evidence-based overview of idiopathic and secondary chilblains, distinguishing features of COVID-19 chilblains, and a systematic clinical approach to history, examination, investigations, and treatment. In the absence of cold or damp exposure, COVID-19 should be considered as a cause of acute chilblains. The timing of onset of COVID-19 chilblains relative to active SARS-CoV-2 viremia remains unclear. Patients with suspected COVID-19 chilblains should thus follow public health guidelines for COVID-19 testing and self-isolation.

Perniosis during the COVID-19 pandemic: Negative anti-SARS-CoV-2 immunohistochemistry in six patients and comparison to perniosis before the emergence of SARS-CoV-2.

BACKGROUND: Acral inflammatory lesions that have some resemblance to idiopathic or autoimmune-associated perniosis (chilblains) have been described in multiple countries during the COVID-19 pandemic. METHODS: We examined histopathologic findings in six consecutive such cases from five patients received in mid-May to mid-June of 2020, evaluating immunohistochemical staining for the SARS-CoV-2 nucleocapsid protein. We compared these six cases to eight cases diagnosed as perniosis between January and June of 2019. RESULTS: Five of six lesions with perniosis-like histopathology during the COVID-19 pandemic had distinctive tight cuffing of lymphocytes; intravascular material was present in one case. SARS-CoV-2 immunohistochemical staining using an antibody directed at the nucleocapsid protein was negative in all six cases. Only one of eight specimens with microscopic findings of perniosis received prior to the COVID-19 pandemic had tightly cuffed perivascular lymphocytes, and none had obvious intravascular occlusion. CONCLUSIONS: A tightly cuffed pattern of perivascular lymphocytes is a feature of perniosis during the COVID-19 pandemic. The absence of SARS-CoV-2 nucleocapsid protein in these cases suggests against the virus being directly present in these lesions.

Treatment of primary perniosis with oral pentoxifylline (a double-blind placebo-controlled randomized therapeutic trial).

Primary perniosis is an annoying cold-induced dermatosis. Many therapeutic agents have been tried with either unsatisfactory or controversial results. The aim of this study was to assess the efficacy of oral pentoxyfylline in the treatment of primary perniosis. A double-blind placebo-controlled randomized therapeutic study conducted in dermatology department of Al-Yarmouk Teaching Hospital, Baghdad, Iraq during four winter seasons between 2010 and 2014. The patients were randomly allocated into two equal groups: group A patients were given oral pentoxyfylline 400 mg thrice daily whereas patients in group B were given an identical placebo tablet thrice daily for 3 weeks. Therapeutic response of both groups was clinically assessed weekly for 3 weeks and side-effects were recorded. A total of 110 patients with chilblains completed this therapeutic trial. The mean age was 24.98 ± 9.17 year. Male to female ratio was 1:2.4. All patients presented with erythematous papules, plaques or nodules. Very good therapeutic response was significantly better for group A than that of group B at 7th, 4th, and 21st days of the trial (p-value: 0.0148, 0.0000004, and 0.0000000, respectively). No side effects were encountered in both groups. Pentoxyfylline is an effective and safe drug for treatment of primary perniosis.

Pattern of chilblains in a high altitude region of Ladakh, India.

BACKGROUND: Extreme sub-zero temperature in winters (15 °C to -25 °C), high velocity winds and wind-chill factor pose risk to those who resides at the high altitude environment to develop cold related injuries like chilblains and frostbite. The aim of this study was to study the patterns of chilblains in high altitude region like Ladakh. METHODS: The study was conducted at Dermatology outpatient department of Military Hospital, Leh from 1 Sep 2009 to 31 May 2010. Patients, satisfying clinical criteria for the diagnosis of chilblains were included into the study. Detailed history and thorough clinical examination was conducted. Complete blood count and Urine routine examination was carried out in every patient. Anti Nuclear Factor tests were carried out in only those who had history suggestive of connective tissue disease. RESULTS: Total 108 (5.75%) were diagnosed to have chilblains. Only a single case of chilblain was found in a local resident (p < 0.005). Family history of chilblains was present in 10 (9.2%) patients, there was recurrence in 12 (11.1%) and 21 patients (19.4%) were smokers. Most (63.8%) of the patients, had BMI between 20 and 22 kg/m(2) (mean = 20.03 kg/m(2); 95% CI = 19.68-20.38 and SD 1.82). 42.1% of cases of chilblains also had hyperhidrosis (p < 0.05). CONCLUSION: In a HA area like Ladakh, the non-natives suffer maximum from chilblains. This could be explained by the protective genetic adaptability of natives to extreme cold environment and their protective life style against cold. Low body mass index (BMI) and hyperhidrosis are important associations for development of chilblains.

Application of Bukuryoingohangekobokuto and Hangekobokuto for Perniosis with Ki Obstruction / 日本東洋医学雑誌

We experienced four cases of perniosis successfully treated with bukuryoingohangekobokuto, or hangekobokuto. Swollen tongue, pulsation at the pit of the navel, and tympanitic abdominal sounds were taken as common objective findings in all four cases. In addition, decreased surface body temperature was diagnosed at the bilateral hands and feet, so as to be distal from the trunk in palpation. These four cases had both symptoms of an eminent Ki obstruction, and a disorder of body fluid metabolism. For the two cases administered bukuryoingohangekobokuto especially, a state of strong Ki deficiency was diagnosed. Efficacy in each case was prompt. Thus, we consider bukuryoingohangekobokuto and hangekobokuto to be prescriptions worth trying for perniosis that does not responding to the usual Western medicines, or Kampo treatment.