Materiały źródłowe

• #1 Erythema Nodosum – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK470369/

  Epidemiology […] EN is the most common clinical form of acute nodular hypodermis. It occurs more often in women between 25 and 40 years but can be observed at any age. Compared to men, women are affected three to six times more. It is rare without sex predominance in the pediatric population. Of worldwide ubiquitous distribution, there is, however, an ethnic and geographical difference in the incidences explained by the variation of triggering etiological factors. Familial cases have been reported and are usually caused by an infectious etiology.

• #2 Erythema Nodosum: A Practical Approach and Diagnostic Algorithm

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7938036/

  Erythema nodosum is the most common form of panniculitis and is characterized by tender erythematous nodules mainly in the lower limbs on the pretibial area. […] The incidence of EN varies according to the triggering factor and its ethnic, racial, and geographic differences. In north-western Spain, the annual incidence rate of biopsy-proven EN for the population aged 14 years and older was 52 cases/million and the incidence was higher in the first half of the year when streptococcal infections are more frequent. […] Among adults, this condition affects women more frequently, with a male:female ratio of~1:5. […] The maximum number of incidences occurs between the second and third decades although it can occur at any age.

• #3 Erythema nodosum – Wikipedia

  https://en.wikipedia.org/wiki/Erythema_nodosum

  Erythema nodosum is the most common form of panniculitis. It is most common in the ages of 20-30, and affects women 3-6 times more than men. […] Erythema nodosum is diagnosed clinically. A biopsy can be taken and examined microscopically to confirm an uncertain diagnosis. […] Additional evaluation should be performed to determine the underlying cause of erythema nodosum.

• #4 Erythema Nodosum: A Sign of Systemic Disease | AAFP

  https://www.aafp.org/pubs/afp/issues/2007/0301/p695.html

  Erythema nodosum occurs in approximately one to five per 100,000 persons. […] In adults, it is more common among women, with a male-to-female ratio of 1:6. […] In children, the sex ratio is 1:1. […] Peak incidence occurs in persons between 20 and 30 years of age, although erythema nodosum can occur at any age. […] All patients with erythema nodosum should be stratified by risk for tuberculosis exposure. […] Appropriate measures include tuberculin skin test, chest radiography, and acid-fast bacilli sputum analysis. […] Erythema nodosum may occur with primary tuberculosis and may even manifest before the development of a skin-test reaction to tuberculin. […] The bacille Calmette-Gurin vaccination and the tuberculin skin test have been associated with the development of erythema nodosum. […] Erythema nodosum is a nonspecific cutaneous reaction pattern to a variety of antigens, with many immune-mediated mechanisms implicated. […] Most direct and indirect evidence supports the involvement of a type IV delayed hypersensitivity response to numerous antigens.

• #5 Erythema Nodosum

  https://mobile.fpnotebook.com/Derm/Rheum/ErythmNdsm.htm

  Incidence: 1-5 per 100,000 […] Age: Peaks in 20-30 year range (up to age 50 years) […] Adults: Women predominate by a factor of 6 fold […] Children: Boys and girls are equally affected.

• #6 Clinicopathological Characteristics Related to Etiologies of Erythema | CCID

  https://www.dovepress.com/clinicopathological-characteristics-related-to-etiologies-of-erythema–peer-reviewed-fulltext-article-CCID

  Erythema nodosum (EN) is the most common form of panniculitis characterized by symmetrical, erythematous, tender, warm nodules and plaques located on the pretibial areas. The incidence of EN is approximately one to five per 100,000 persons with a male-to-female ratio of 1:1 in children and 1:5 in adults. Although EN can occur in any age group, it is most frequently found in the second to fourth decades of life. EN is considered a hypersensitivity response to various antigens from a wide range of precipitating factors such as infection, inflammation, neoplasm, and drugs. […] EN can be classified according to the etiologies as primary or idiopathic EN and secondary EN when there is an identifiable cause. Conditions related to secondary EN remain inconclusive and vary according to triggering factors in the study period, ethnic, racial, and geographic differences. Regarding the clinical course, both idiopathic and secondary EN can resolve spontaneously within approximately 3-6 weeks without scarring. Few studies have shown that idiopathic EN tends to recur more frequently than secondary EN.

• #7 Erythema Nodosum: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1081633-overview

  In the United States, the peak incidence of EN is between the ages of 18 and 34 years, though it has been known to occur in children and in individuals older than 70 years. Age and sex distributions vary according to etiology and geographic location. […] Women are affected more often than men, with a male-to-female ratio of approximately 1:5. […] Globally, the incidence of EN varies by country. In England, the rate has been reported as 2.4 cases per 10,000 per year.

• #8 Erythema nodosum

  https://escholarship.org/uc/item/4829t6rn

  Erythema nodosum is the most frequent clinico-pathological variant of the panniculitides. […] Erythema nodosum is a cutaneous reactive process that may be triggered by a wide variety of possible stimuli. Infectious diseases, sarcoidosis, rheumatologic diseases, inflammatory bowel diseases, medication reactions, autoimmune disorders, pregnancy, and malignancies the most common associated conditions. […] Several studies have demonstrated that erythema nodosum occurs three to six times more frequently in women than in men, however, the sex incidence before puberty is approximately equal. […] Prevalence of erythema nodosum in a semirural area of England over a 2-year period gave a figure of 2.4 per 1000 population per year. […] Prevalence varies also according to the type of the patients attended to in a clinic: the average hospital incidence was about 0.5 percent of new cases seen in Departments of Dermatology in England and about 0.38 percent of all patients seen in a Department of Internal Medicine in Spain.

• #9 Erythema Nodosum in Children: A Narrative Review and a Practical Approach

  https://www.mdpi.com/2227-9067/9/4/511

  Erythema nodosum (EN) is the most frequent form of panniculitis in children. […] The estimated prevalence of EN in the world is 1–5 per 100,000, varying upon the different geographic areas and the various associated triggering diseases. […] A higher incidence (12–14 cases/100,000) was reported in Scandinavia. […] It can manifest in all racial groups and ages, being more common between 18 and 40 years; in contrast, it is rare in pediatric age and exceptional in children before the age of 2 years. […] In adults, the females–males ratio is 3–5:1. […] In children under 12 years, there is no prevalence of gender, while in adolescence, females are prevalent. […] The female prevalence suggests that estrogen may be involved in the pathogenesis. […] Furthermore, familiarity has been described. EN has been described as manifesting itself in several members with the same HLA.

• #10 Erythema nodosum

  https://escholarship.org/uc/item/4829t6rn

  In a recent study, the average annual incidence rate of biopsy proven erythema nodosum in a hospital of the northwestern Spain for the population 14 years and older was 52 cases per million of persons, although certainly this rate underestimated the authentic incidence of the disease because only included cases confirmed by biopsy. […] Most cases of erythema nodosum occur within the first half of the year, probably due to the more frequent incidence of streptococcal infections in this period of the year, and there is no difference in distribution between urban and rural areas. […] Familial cases are usually due to an infectious etiology.

• #11 Erythema nodosum – Altmeyers Encyclopedia – Department Dermatology

  https://www.altmeyers.org/en/dermatology/erythema-nodosum-119277

  Panethnic. Most common septal panniculitis. Prevalence in Central Europe: 100-200/100.000 inhabitants/year. Incidence in Central Europe: 2-8/100,000 inhabitants/year.

• #12

  https://step1.medbullets.com/dermatology/115058/erythema-nodosum

  Epidemiology […] incidence […] the most common panniculitis […] demographics […] female male […] peak incidence between 20-30 years of age […] risk factors […] infection […] autoimmune disease […] leprosy […] […] […] erythema nodosum typically resolves spontaneously and fades over 1-2 months

• #13 Erythema nodosum – UpToDate

  https://www.uptodate.com/contents/erythema-nodosum

  Erythema nodosum (EN) occurs in all ages, sexes, and racial groups but is most common in women in their second to fourth decades. Women are affected three to six times more often than men. The specific incidence of EN varies based upon the local prevalence of the associated triggering diseases. […] The etiologies, diagnosis, and management of EN will be reviewed here.

• #14 Erythema Nodosum | 5-Minute Pediatric Consult

  https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617457/all/Erythema_Nodosum?q=Histoplasmosis

  Girls slightly more frequently affected than boys. […] Incidence peaks in adolescence and is rare 2 years of age.

• #15 Erythema nodosum – Cancer Therapy Advisor

  https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/hospital-medicine/erythema-nodosum/

  Epidemiology […] EN is considered to be a delayed hypersensitivity response to a variety of antigenic stimuli, including infections, medications, pregnancy, and inflammatory and malignant disease. EN is the most common type of panniculitis is all ages. Its peak incidence is between 20 and 30 years of age, with a smaller peak in adolescence, particularly in children older than 10 years of age. […] Although there is a clear female predominance in adults with EN, during childhood, girls are affected only slightly more than boys, and most studies and reviews report an equal sex incidence. It is rare in children younger than the age of 2 years. The greatest incidence is seen in the spring and fall. Although seen in the summer, it is less common during that season. […] In the past, tuberculosis was the most common cause associated with EN. In the United States and Europe, -hemolytic streptococcal infection is now the most common inciting agent. In cases of EN with undefined causes, it is often reported that a respiratory tract infection occurred before skin manifestations. […] Racial and geographic differences of incidence vary depending on the prevalence of diseases that are causative factors. In areas where certain causes of EN are prevalent (e.g., Coccidioides immitis, Behet disease), EN may be seen in greater numbers.

• #16 Erythema Nodosum Epidemiology: 5-Years Retrospective Study – Turkish Journal of Dermatology

  https://turkjdermatol.com/articles/erythema-nodosum-epidemiology-5-years-retrospective-study/doi/tdd.2012.19

  Erythema nodosum (EN) is the most common type of septal panniculitis. […] Factors are changing from region to region and from country to country. […] Fifty-two of 66 patients had underlying etiologic factors (Group 1) and 14 of were idiopatic (Group 2). […] Most common etiologic factor was Behets disease (n=15), and followed by drug (n=13), sarcoidosis (n=10), upper respiratory tract infection (n=6), autoimmune disease (n=4), pregnancy (n=2), tuberculosis (n=2) in decreasing frequencies. […] In our study malignancy and inflammatory bowel disease are not appointed. […] Behcets disease is a rare cause of EN. […] In our study because of finding the common etiologic factor as Behets disease due to being of Behets disease high prevalance (11-42/10000) in our country and existence of Behets disease center in our faculty.

• #17 An aetiological analysis of erythema nodosum in a community hospital – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/an-aetiological-analysis-of-erythema-nodosum-in-a-community-hospital/

  Erythema nodosum (EN) is a reaction pattern in the skin characterized by septal panniculitis. Infectious diseases are most common cause of EN. This study was aimed to find out the most common causes for EN as seen in a community hospital over a period of two years. […] Though the number of patients is small, it still establishes the fact that tuberculosis continues to be the most common cause of EN. […] This study, though small, was done in a community hospital (catering to middle income group of people) and point out certain interesting facts. The age and sex incidence and the clinical characteristics of EN seen in our series, were in accordance with literature findings. […] The cause of EN was suggestive in 11 patients, (nearly 80%). The rest 20% responded to empirical treatment without recurrence.

• #18 An aetiological analysis of erythema nodosum in a community hospital – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/an-aetiological-analysis-of-erythema-nodosum-in-a-community-hospital/

  Tuberculosis is no longer a cause of EN in USA and Europe. But in our series, tuberculosis was the major culprit. Nearly 7 out of 11 showed tuberculous aetiology. […] Many infectious diseases associated with EN have been described, but it is virtually impossible to investigate all possible causes in patients presenting with EN, without specific symptoms. […] Similarly, newer causes of EN described in the past decade include Human immunodeficiency virus (HIV) and Hepatitis C virus (HCV). It was not done in our cases as there was no clinical evidence of these. […] Other systemic diseases presenting with EN include collagen vascular disorders and malignancies. We had only one lady with SLE and 2 cases with polyarteritis nodosa. No malignancies were seen as the aetiological factor in our patients.

• #19 Erythema nodosum | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/erythema-nodosum?embed_domain=external.radpair.com%27%5B0%5Dfavicon.icoradiopaedia-icon-144.png&lang=us

  Erythema nodosum is three to five times more common in female patients 1. […] Erythema nodosum appears as painful erythematous nodules over the shins approximately 1-6 cm in size and are usually distributed symmetrically. […] Systemic symptoms (e.g. fever) may also be present depending on the underlying condition 1.

• #20 Erythema nodosum: Symptoms, Causes, and Management — DermNet

  https://dermnetnz.org/topics/erythema-nodosum

  Erythema nodosum can occur in all ethnicities, sexes, and ages, but is most common in women between the ages of 25 and 40. It is 36 times more common in women than in men except before puberty when the incidence is the same in both sexes. […] Erythema nodosum is primarily a clinical diagnosis confirmed by laboratory tests and histopathology. The pathology of erythema nodosum shows inflammation primarily of the septa between the subcutaneous fat lobules without vasculitis. […] Erythema nodosum follows a relatively benign and favourable course. It is important to recognise the underlying cause, if any, and initiate symptomatic treatment. Most cases resolve within days to weeks. Relapses may occur in approximately one-third of cases erythema nodosum may become a chronic or persistent disorder lasting for 6 months and occasionally for years.

• #21 Erythema nodosum – UpToDate

  https://www.uptodate.com/contents/erythema-nodosum/print

  Erythema nodosum (EN) is a delayed-type hypersensitivity reaction that most often presents as erythematous, tender nodules on the shins. EN occurs in all ages, sexes, and racial groups but is most common in women in their second to fourth decades. Women are affected three to six times more often than men. The specific incidence of EN varies based upon the local prevalence of the associated triggering diseases. […] The characteristic histologic finding in EN is a septal panniculitis without vasculitis. EN usually resolves spontaneously within several weeks.

• #22 Erythema nodosum

  https://www.pcds.org.uk/clinical-guidance/erythema-nodusum

  Erythema nodosum (EN) is characterised by painful, erythematous, and sometimes bruised-looking, nodules on the anterior surface of the legs. It is a type of panniculitis, ie an inflammatory disorder of the subcutaneous adipose tissue, affecting 1-5 in 100 000 population per year. […] EN is usually diagnosed clinically, however, in atypical cases (eg absence of lesions on the legs, persistence or ulceration of lesions) an elliptical biopsy is needed, which shows a predominantly septal panniculitis without vasculitis. […] Investigations required in EN include: Throat swab and ASO titre for streptococcus, Urinalysis, Blood tests – FBC and inflammatory markers, CXR for TB and sarcoidosis, Other tests depending on suspected aetiology.

• #23 Erythema Nodosum – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-reactive-skin-disorders/erythema-nodosum

  Erythema nodosum primarily affects people in their 20s and 30s but can occur at any age; women are more often affected. […] Up to about 50% of cases of erythema nodosum are idiopathic. […] A diagnosis of erythema nodosum should prompt evaluation for causes. Evaluation might include biopsy, tuberculosis skin testing (using purified protein derivative [PPD] or anergy panel), and possibly other tests (eg, antinuclear antibodies, complete blood count, chest radiograph, and serial antistreptolysin O titers or a pharyngeal culture). […] The most common causes of erythema nodosum are streptococcal infections (particularly in children), sarcoidosis, and inflammatory bowel disease. […] Diagnose erythema nodosum primarily by clinical appearance but, when necessary, incisional wedge biopsy may be performed for confirmation.

• #24 Erythema Nodosum | Doctor

  https://patient.info/doctor/erythema-nodosum-pro

  The prevalence of erythema nodosum varies from country to country. It is approximately five times more common in adult women than in adult men and the peak incidence is between the ages of 20 and 40, although it can occur at any age. In children, the incidence is equal in boys and girls. […] Although in many cases it is idiopathic, it is important to exclude serious underlying disease.

• #25 Erythema Nodosum: Causes, Symptoms, and Treatment

  https://patient.info/skin-conditions/erythema-nodosum

  Erythema nodosum is rare. It affects between 2 and 3 in every 10,000 people per year. […] In over half of people who develop erythema nodosum, no cause for the inflammation is found. […] However, in some people there may be something that triggers the inflammation. […] Erythema nodosum may be the first sign of a serious underlying condition that needs to be identified and treated. […] If your doctor diagnoses erythema nodosum, they will usually suggest some tests to look for an underlying trigger. […] The treatment depends on the trigger. […] Generally, the outlook for erythema nodosum is very good and most people do not have further problems.

• #26 Erythema Nodosum | Concise Medical Knowledge

  https://www.lecturio.com/concepts/erythema-nodosum/

  Erythema nodosum (EN) is most common in women in their 2nd-4th decades. […] Women are affected 36 times more often than men. […] All ages and racial groups can be affected. […] Half of cases have an unknown etiology. […] Infection is the most commonly identified cause, especially streptococcal infection, but other bacteria, as well as fungi and viruses, are known etiologic agents, including coronavirus disease 2019 (COVID-19) (rare). […] Erythema nodosum can offer clues to the presence of a serious underlying treatable disease, such as streptococcal infection, sarcoidosis, tuberculosis, and coccidioidomycosis. […] EN may have prognostic value in a few situations because it is associated with a lower incidence of disseminated disease in coccidioidomycosis. […] EN may precede or be coincident with an acute flare of inflammatory bowel disease.

• #27 Erythema nodosum – BAD Patient Hub

  https://www.skinhealthinfo.org.uk/condition/erythema-nodosum/

  Most patients with EN make a full recovery within a few weeks or months. Relapses may occur in approximately one third of cases with the condition persisting and becoming a chronic disorder lasting for 6 months or even years. […] Your doctor will look for known triggers for EN and treat the underlying cause. If an infectious cause is identified, then antibiotic treatment may be given. If a particular medication is suspected as the trigger, it may be stopped. For most people with EN the rounded lumps tend to heal spontaneously within 3 to 8 weeks. Some patients may need treatment to relieve symptoms, such as bed-rest, leg elevation, and anti-inflammatory painkillers (non-steroidal anti-inflammatory agents). For more prolonged or frequently occurring EN, a number of other treatments may be used such as steroid tablets.

• #28 Around Half of Erythema Nodosum Patients Report Chronic, Recurrent Disease

  https://www.hcplive.com/view/around-half-of-erythema-nodosum-patients-report-chronic-recurrent-disease

  Around half of those with the inflammatory skin disorder erythema nodosum (EN) report chronic or recurrent disease, according to a recent analysis, and 26% of this half of EN patients showed incomplete response to treatment. […] The investigators looked into data related to disease presentation, demographic information, workup, comorbidities, EN triggers, treatments, and patient responses. […] They classified classic EN as symptom resolution within 12 weeks and chronic/recurrent EN as EN with symptoms continuing or recurring for 12 weeks or more. […] Those in the chronic/recurrent EN were shown by the investigators to, compared to those with classic, have more frequently needed several different treatments to reach clinical response (42% compared to 25%; P.001). […] Systemic therapy was necessary in 64% of patients with chronic/recurrent EN, compared to 48% in patients with classic EN (P=.003), and incomplete response to treatment was found to have occurred in 26% and 1%, respectively (P.001). […] Further studies are warranted to identify risk factors leading to chronicity/recurrence of EN, results of autoantibody testing, and ideal management strategies.

• #29 A Systematic Review on the Epidemiological Data of Erythema Nodosum Leprosum, a Type 2 Leprosy Reaction | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002440

  Erythema Nodosum Leprosum (ENL) is a humoral immunological response in leprosy that leads to inflammatory skin nodules which may result in nerve and organ damage, and may occur years after antibiotic treatment. Global occurrence is unknown. […] Although adequate surveillance systems are used to estimate global leprosy prevalence and inform drug supply, this is not available for estimating incidence, frequency and severity of ENL. […] This review has established that reliable data on ENL occurrence is lacking, and could only be obtained through large comprehensive prospective studies or data obtained from accurate ENL surveillance.

• #30 Erythema Nodosum Leprosum (Leprosy) – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/erythema-nodosum-leprosum-leprosy/

  Borderline and lepromatous leprosy patients are susceptible to ENL reactions, which can occur before, during or after treatment with multidrug treatment (MDT). ENL is more prevalent in Southeast Asia and Brazil (25-49% of LL cases), when compared to Africa (5%), probably due to genetic variations. For instance, Brazilian patients who were homozygous C4B-deficient had a higher prevalence of ENL. It was hypothesized that the absence of the C4B allele may impair immune complex clearance and trigger ENL. […] Risk factors include lepromatous leprosy, bacillary index 4+, multi-drug therapy (MDT), medications (antibiotics), infections (screen the patient for subclinical infections, such as dental cavities), pregnancy, lactation, psychological stress, and vaccinations (All vaccinations may stimulate a systemic immune inflammatory response).

• #31 Outbreak of Erythema Nodosum of Unknown Cause — New Mexico, November 2007–January 2008

  https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5848a3.htm

  Erythema nodosum (EN) is a form of panniculitis, which has been associated with several infectious and noninfectious etiologies. EN clusters have been associated with outbreaks of Coccidioides immitis, Histoplasma capsulatum, and Yersinia pseudotuberculosis infections. NMDOH initiated an investigation to confirm the existence of the outbreak, determine the underlying etiology, and implement control measures. During an EN outbreak, timely (acute and convalescent) specimen collection (ideally from case-patients and control subjects to determine baseline seropositivity) and sensitive tests (e.g., polymerase chain reaction [PCR]) are essential to differentiate among possible causes of EN. This investigation confirmed an EN outbreak in a rural community in New Mexico during the winter of 2007-2008. Despite extensive assessment for known etiologies and associated illnesses, no etiology for the outbreak could be found. Investigation of an outbreak of 25 cases of EN in a rural community in New Mexico did not identify an etiology despite an extensive search for known causative agents. During an EN outbreak, timely specimen collection and sensitive tests (e.g., polymerase chain reaction) are essential to differentiate among possible causes of EN. This is the first reported EN cluster with unknown cause.

• #32 The relationship between erythema nodosum and prognosis in systemic sarcoidosis: a retrospective cohort study | Anais Brasileiros de Dermatologia (Portuguese)

  https://www.anaisdedermatologia.org.br/pt-the-relationship-between-erythema-nodosum-articulo-S0365059622001118

  Erythema Nodosum (EN) is the most common skin manifestation in sarcoidosis and has often been associated with a good prognosis. […] The prevalence of sarcoidosis is 4.764 in 100.000 people and the incidence is 135.5 in 100.000 people per year with the highest frequency observed in Northern European and African-American individuals. […] Early studies indicate that EN is associated with a good prognosis in sarcoidosis. […] The lower radiological stage of pulmonary sarcoidosis and lower frequency of systemic organ involvement in patients with EN augment the prognostic value of EN highlighted in the literature. […] EN is characterized by erythematous-violaceous tender nodules on the extensor aspects of the lower legs and has often been associated with a good prognosis in previous studies.

• #33 The relationship between erythema nodosum and prognosis in systemic sarcoidosis: a retrospective cohort study | Anais Brasileiros de Dermatologia (Portuguese)

  https://www.anaisdedermatologia.org.br/pt-the-relationship-between-erythema-nodosum-articulo-S0365059622001118

  The significantly lower radiological stage of pulmonary sarcoidosis in patients with EN in the present study population supports the prognostic value of EN highlighted in previous studies as the higher stage of chest radiography is associated with a worse prognosis. […] In relation to this, fever was the only constitutional symptom that was more common in the EN group in the present study’s sample, even though the difference was not statistically significant. […] Regarding organ involvement, neurological involvement was significantly less common in patients with EN (0.0% vs. 13.2%, p = 0.036) in the present study’s cohort, and to our knowledge, this has not been previously mentioned in the literature. […] In the present study, the percentage of patients who received systemic therapy was lower in the EN group (29.0% vs. 45.1%); however, the difference was not statistically significant. Therefore, although the present authors of this study agree that systemic organ involvement is less common in patients who had EN as an initial presenting symptom, the authors couldn’t confirm that these patients would need less systemic therapy in the course of their disease.

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