Rates of New Peanut Allergy and Discontinuation Following Introduction in High-Risk Infants

Rationale: Current guidelines recommend peanut introduction to high-risk infants. However, compliance and rates of new peanut allergy (PA) require further study. Methods: Participants aged 4-11 months with no prior peanut exposure and (i) diagnosis of non-peanut food allergy, (ii) moderate-severe atopic dermatitis, or (iii) first degree relative with PA were enrolled. PA status was determined by skin testing and food challenge. Participants without PA were advised to consume 2 grams of peanut protein three times/week. Monthly questionnaires were administered, with follow-up visits at 18 and 30 months. Results: At baseline, 35/326 (11%) participants were peanut allergic. Of 291 without PA, 78 (27%) discontinued peanut at least temporarily 115 times during follow-up because of suspected participant reaction (40%), fear of reaction (3%), reaction or fear of reaction in a family member (21%), participant refusal (9%), peanut introduction was too much work (3%), or other reasons (23%), including the COVID-19 pandemic. Six of 291 participants (2.1%) who consumed peanut developed PA (2 consistent with FPIES). Among 291 participants without PA at baseline, none of the 17 participants with initial skin prick test of at least 4 mm and <10 mm developed PA. Conclusions: New PA after early introduction recommendations was rare, confirming the LEAP study findings. Transient discontinuation was common, mostly due to suspected participant reaction. High-risk children may require substantial support to keep peanut in their diet.

Real-Life Effectiveness and Safety of Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: A Single-Center 16-Week Study.

INTRODUCTION: The treatment of severe atopic dermatitis (AD) includes cyclosporine and recently approved biologics and small molecules. Among these, upadacitinib is a selective inhibitor of Janus kinase 1, approved for the treatment of severe AD in adolescents/adults. Upadacitinib has shown efficacy and safety in several phase 3 clinical trials, but data on real-life patients are still lacking. METHODS: We conducted a retrospective real-life observational study to evaluate the effectiveness and safety of upadacitinib up to week 16 in a cohort of both bio-naïve and bio-experienced patients. This study was carried out by analyzing the AD database records of an Italian referral hospital. Thirty-eight patients were included in this study, and 35 completed 16 weeks of treatment. RESULTS: At week 16, out of 35 patients, the percentages of Eczema Area and Severity Index (EASI) 50, EASI 75, EASI 90 and EASI 100 responses were 94.29, 91.43, 74.29, and 60%, respectively. A decrease of at least 4 points from baseline of itch-NRS was reported by 94.74 and 91.43% of patients at weeks 8 and 16. Regarding the safety of upadacitinib, 26.32% of patients experienced at least one adverse event (AE), and a total of 13 AEs were recorded, including blood test abnormalities and papulopustular acne. None of our patients interrupted the drug because of an AE. CONCLUSIONS: We observed higher rates of EASI75/EASI90/EASI100 responses at week 16, compared with data from clinical trials. The safety profile of upadacitinib was favorable, as no AEs leading to discontinuation were experienced by our patients up to week 16.

Sensitivity to treatment and score bands of the Infants and Toddlers Dermatology Quality of Life questionnaire.

Background: The Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire is the first dermatology-specific proxy health related QoL instrument for children from birth to 4 years. Score meaning bands and the sensitivity to successful therapeutic intervention are important to interpret the clinical meaning of an instrument. Objective: The aim of the present study was to check the sensitivity to successful therapeutic intervention and establish score bands of the InToDermQoL questionnaire. Methods: Parents or grandparents of 424 children with skin diseases from Spain, Malta, Croatia, Romania, Greece, and Ukraine filled in national language versions of the InToDermQoL questionnaire. Disease severity of children with atopic dermatitis was assessed by SCORAD (Scoring atopic dermatitis). Cohen's d was used to assess the responsiveness of the instrument. Results: The mean total InToDermQoL scores significantly decreased after treatment. Severity grading of the SCORAD scores gave stratification of the InToDermQoL severity grades based on 95% confidence intervals. Scores below a calculated minimal important difference of 2 corresponded to no effect on patient's health related QoL. Limitations: Score banding may be slightly different across patient population and study context. Conclusion: All 3 age-specific versions of the InToDermQoL questionnaire showed sensitivity to treatment. Score bands for the InToDermQoL questionnaire have been established.

Acceptance of skin products in healthcare workers: an empirical investigation.

BACKGROUND: Healthcare workers (HCWs) are at high risk of developing hand eczema (HE). This can be exacerbated by hygiene measures related to the coronavirus disease (COVID-19). Using mild skin cleansers and emollients or moisturizers is central in the prevention of HE-especially with increased COVID-19 hygiene regimes. AIMS: This study aimed to assess parameters important for the acceptance of a skincare concept in HCWs. METHODS: In this proof-of-concept user trial, HCWs were provided ad libitum with hand wash oil and hand cream during the 6-month period, when occupationally acquired COVID-19 infections among HCWs were peaking in Germany and then surveyed about acceptance of the products using questionnaires. RESULTS: Of 135 HCWs, 115 (85%) responded. Skin tolerance of the hand wash oil and the hand cream was rated very good by 63% and 52% of the 115 participants, respectively. Of the 115 participants, 58% and 57% were very satisfied with the hand wash oil and the hand cream, respectively. CONCLUSIONS: Acceptance of skin cleansing and skincare products in HCWs seems influenced by parameters such as self-assessed skin tolerance and self-reported overall satisfaction. It must be assumed that products are only used as recommended if they are well-accepted. Employers might survey employees about acceptance of products using the parameters identified to adjust concepts if necessary to sustainably contribute to the prevention of HE.

Epidemiology of Occupational Contact Dermatitis (OCD) on health workers in Covid-19

Background Generally, the diagnosis of OCD can be considered after a history of exposure to the suspected material and a thorough physical examination. Meanwhile, vital information about it is often overlooked during the initial consultation. Objective Evaluating the epidemiological profile of OCD cases in health workers due to the COVID-19 pandemic and evaluating complaints, manifestations and causative materials of OCD cases in health workers at the isolation ward of Dr. Soetomo Surabaya Hospital during the Covid-19 pandemic. Methods Purposive sampling was used to design research samples from accessible populations that matched the inclusion requirements while those who met exclusion criteria were included as research samples. Results Majority OCD patients are women and the most common age range is between 22-35 years old. The occupation most affected by OCD while working at isolation ward during the pandemic is nurses. The most common complaint is itching followed by redness of the skin which appears most frequently on the hands. The most prominent clinical manifestations are desquamation followed by erythema-like skin lesions. Medical gloves are the sort of personal protection equipment that causes OCD the most, followed by hand hygiene activities. High risk factors for OCD include a family history of atopic illnesses, history of asthma and an early history of atopic dermatitis. Conclusion The use of PPE can cause several effects on the skin such as physical trauma to the skin, acne, contact dermatitis, urticaria, and aggravate previous skin diseases. The most common skin disorders are erythema, papules, scales, fissures, erosions, ulcers, vesicles and wheals. Complaints of contact dermatitis can be reduced and prevented by taking preventive measures in the form of using moisturizers on areas that are often exposed. Copyright © 2023 Pakistan Association of Dermatologists. All rights reserved.

Three Cases of Disseminated Erythematous Papules with Elevated Serum Thymus and Activation-Regulated Chemokine Levels after COVID-19 Vaccination.

Case 1 was an 81-year-old man undergoing treatment for the nummular eczema of the lower leg. The day after being administered the first dose of a COVID-19 vaccine, the patient developed generalized pruritus, multiple serous papules, and erythema on the trunk, upper extremities, and palms, as well as worsening of pre-existing eczema on the lower legs. The serum TARC level of the patient was 1,383 pg/mL. After taking oral antihistamines and topical steroids for two weeks, the erythema faded, papules crusted, and serum TARC level normalized. Case 2 was a 22-year-old woman who had been treated with topical steroids for contact dermatitis by poultices on the ankles. On the same day as she received the second dose of COVID-19 vaccine, erythema with pruritus on the dorsum of the feet appeared and gradually expanded to papules and edematous erythema on the face, extremities, and trunk. The serum TARC level of the patient was 2,090 pg/mL. After taking 15 mg/day oral prednisolone and topical steroids for 10 days, overall erythema became hyperpigmented, and the erythema on the dorsum of the hands and fingers persisted for approximately 2 weeks and then became pigmented. Serum TARC level normalized after the skin rash reformed. Case 3 was a 74-year-old woman with a history of asthma. She received SBT/ABPC therapy for acute cholangitis for one week. Ten days after treatment, she received the first COVID-19 vaccination dose. Two days after vaccination, the patient became aware of pruritus on the extremities ipsilateral to the vaccination site, and small erythematous patches appeared all over the body in a disseminated pattern. Her serum TARC level was 3,862 pg/mL. After taking oral antihistamines and topical steroids for 3 weeks, the erythema completely faded, and the serum TARC level normalized. The DLST showed positive by SBT/ABPC, but the result of drug challenge test was negative. There have been no previous case reports of rash with a high TARC level after vaccination. In the future, it is necessary to accumulate patients with a high TARC level by vaccination and analyze the clinical and pathological trends including immunological mechanisms. Copyright © 2022 Osaka University Medical School. All rights reserved.

The risk of occupational contact dermatitis in COVID-19 isolation ward setting

Background The preventive measures of coronavirus disease-19 (COVID-19) transmissions require the healthcare workers (HCWs) to be more cautious. Irritants or allergens exposure from these measures might induce adverse skin reactions and lead to the development of occupational contact dermatitis (OCD). Methods Questionnaires were distributed to HCWs in COVID-19 isolation ward of Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. The questionnaire consisted of personal and work characteristics, clinical history, skin complaints, and occupational exposures. Results Fifty-three completed questionnaires were gathered from eligible subjects. History of atopic dermatitis (AD) was found on 8 subject (15.09%). Many of the subjects had complained of dry skin (28.30%), itchy skin (26.41%), and redness of skin (20.75%) on the hands in the last 12 months. As many as 50.94% of the subjects washed their hands with water and soap at least 6-10 times a day and 49.06% used hand sanitizers 6-10 times a day. The use of PPE were mostly 4 hours a day or less. There were associations between history of AD with complaints related to hand dermatitis (p=0.004) and history of AD with incidence of OCD assessed with Mathias criteria (p=0.016). It was also found that the use of gloves for 2 or more hours a day was associated with skin complaints after gloves use (p=0.021) and the use of hand sanitizer for more than 10 times a day was associated with complaints related to hand dermatitis (p=0.041). Conclusion The repeated and prolonged exposure to irritative or allergenic substances contained in PPE and hand hygiene products is related to OCD, particularly hand dermatitis, among HCWs in COVID-19 isolation ward. Copyright © 2023 Pakistan Association of Dermatologists. All rights reserved.

Systemic lupus erythematosus cutaneous flare following COVID-19 vaccination: A case report

Objective: To present a case of a SLE cutaneous flare following COVID-19 vaccination in a patient with low disease activity Background: Disease flare in a patient with underlying autoimmune rheumatic disease (AIRD) after vaccination had already been experienced with other vaccines, such as influenza, hepatitis B, and HPV vaccines. Given the relatively unknown safety profile of the COVID-19 vaccine among patients with AIRD, the probability of a disease flare is not a remote possibility. Several case reports available had already reported few cases of AIRD disease flare following vaccination, some of which requiring escalation of the treatment regimen. Molecular mimicry, as had been described with other vaccines, is still implicated as the possible explanation for such a phenomenon. Case: A 57 year old female with systemic lupus erythematosus with nephritis since 1994 with low disease activity, maintained on hydroxychloroquine and low dose methylprednisolone daily who developed multiple well-defined elevated erythematous and pruritic plaques on both thighs, spreading to the face, scalp, trunk, and extremities 3 weeks after receiving her first dose of viral vector vaccine. Work-ups included eosinophilia on CBC, elevated ESR, anti-dsDNA, ferritin, and LDH, with low C3, with proteinuria and hematuria on urinalysis. She was admitted and her glucocorticoid was increased and tapered accordingly. Skin punch biopsy with alcian blue staining was also done which revealed interface dermatitis consistent with lupus erythematosus. Few days after increasing her glucocorticoid, cutaneous lesions gradually resolved and she was discharged improved. She received her second dose of vaccine 2 months after her first dose with no reported incidents of adverse events. Conclusion(s): This is one of the few cases of a reported SLE flare confirmed by disease activity index and biopsy-confirmed skin rashes. The development of such an adverse reaction to a vaccine may be relatively low but still possible due to intricate interaction of the immune system and vaccine.

A case report of IgA vasculitis following CoronaVac vaccination in a Filipino patient

Introduction: Coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV- 2) are emerging. There is an urgent need for COVID-19 vaccines to control disease outbreaks by herd immunity. Vaccines can trigger immunity as many vaccine-related immunological adverse events have been described. Case Presentation: A case of a 32 years old Filipino female with no known co-morbidity who presented with rashes on bilateral lower extremities one day after receiving her second dose of CoronaVac-Sinovac vaccine. These were non-pruritic nor painful, which appeared to be initially well-defined round erythematous macules, papules, and plaques, mostly raised. It was associated with colicky abdominal pain and inflammatory arthritis affecting the both knees and ankles. She has no vices but known to have allergy with seafood. There were multiple well defined erythematous round to irregularly shaped purpuric macules, papules and plaques, non-blanching, flat and raised, on arms near the antecubital fossa, abdomen and lower extremities. She underwent skin biopsy and direct immunofluorescence showed interface dermatitis with leukocytoclastic vasculitis and IgA +1 vessel wall, and fibrinogen +2 vessel wall, respectively. There was microscopic hematuria and proteinuria. The Urine protein creatinine ratio was normal at 0.193 gm/gm. She was managed as a case of IgA vasculitis and was given moderate dose of steroid (0.5mg per kilogram per day prednisone equivalent) and omeprazole. She was discharged improved with resolution of rashes evident during follow up at the out-patient consultation. Conclusion(s): We report a case of an adult Filipina developing IgA vasculitis following CoronaVac COVID-19 vaccination. She responded well following initiation of steroid therapy. Autoimmune phenomenon following immunization is possible through different mechanisms. These include molecular mimicry, a hyper-stimulated inflammatory state, and autoimmune syndromes induced by adjuvants. While no strategies have been found to prevent autoimmunity following vaccination, it should be emphasized that vaccine recipients should seek medical care for any untoward events following receipt of any immunization.

Comparison of Malassezia Colonization of 'Maskne' Patients with Seborrheic Dermatitis Cases and Healthy Individuals.

Background: With the Covid-19 pandemic, the use of masks has increased the frequency of 'maskne' cases. Local physiological changes due to the use of mask have caused changes in the presence of yeasts in the environment, such as acne and seborrheic dermatitis. Objectives: The aim is to compare the differences of Malassezia species in the maskne region. Materials and Method: A total of 408 subjects wearing masks at least 4 h a day for 6 weeks or longer, compromised of 212 acne patients, 72 seborrheic dermatitis sufferers, and 124 healthy volunteers were included in this study. Swab samples were taken for Malassezia cultures from nasolabial area and their control retro auricular region. The Statistical Package for Social Sciences (SPSS) version 22 was used for the statistical analysis. Results: Malassezia species was most frequently found in the nasolabial region of the seborrheic dermatitis group. Malassezia species were more commonly isolated from the nasolabial region of acne and seborrheic dermatitis patients, compared to the retroauricular region of each patient, than the healthy subjects. The rate of M. globosa isolated from the nasolabial region was high in all groups, the isolation rate of M. restricta was low (P < 0.05). Conclusion: As Malassezia species are more commonly isolated from the nasolabial region of acne and seborrheic dermatitis patients, the increasing numbers of Malassezia species will trigger inflammation with an antibody reaction against these yeasts. Treatment of resistant acne and seborrheic dermatitis will be facilitated with the knowledge of this inflammation.

Concomitant Severe Psoriasis and Bullous Pemphigoid Induced by COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first isolated in Wuhan, China, is currently a pandemic. At the beginning of the pandemic, pulmonary issues were the most discussed and studied. However, now 3 years later, the role of the dermatologist has become increasingly central. Often the diversity in the presentation of these manifestations has made it difficult for the dermatologist to recognize them. In addition to the common symptoms involving fever, cough, dyspnea, and hypogeusia/hyposmia that have been widely discussed in the literature, much attention has been paid to dermatologic manifestations in the past year. The vaccination campaign has been the most important strategy to combat the COVID-19 pandemic. Specifically, two viral vector-based vaccines [Vaxzervria® (AstraZeneca; AZD1222) and COVID-19 Janssen® vaccine (Johnson & Johnson; Ad26.COV2. S)] and two mRNA-based vaccines [Comirnaty® (Pfizer/BioNTech; BNT162b2) and Spikevax® (Moderna; mRNA-1273)]. However, several cutaneous adverse reactions have been reported following vaccination, making the dermatologist's role critical. It is possible to group these adverse reactions according to a classification with six main clinical pictures: urticarial rash, erythematous/maculopapular/morbid rash, papulovesicular rash, chilblain-like acral pattern, livedo reticularis/racemose-like, and purpuric "vasculitic" pattern. Beyond this classification, there are several reports of other dermatologic manifestations associated with the infection, such as pityriasis rosea, herpes zoster, or, particularly, the worsening of pre-existing chronic inflammatory dermatologic diseases. Here we report the case of a 61-year-old patient who presented at our clinic with a diffuse psoriasiform eruption mixed with a concomitant blistering rash induced by COVID-19. The uniqueness of our case has two features: the first is the concomitance of the two events after infection that seems to be unprecedented; the second is the management of the patient that could help dermatology colleagues in the management of these conditions during infection.

The flip side of frequent sanitising and hand washing.

The stratum corneum is the outermost layer of the epidermis. It acts as an interface with the external environment and functions as a barrier that prevents microorganisms and allergens from penetrating the skin, while preventing bodily fluids, electrolytes and proteins from being lost in a process aimed at maintaining homeostasis. With the novel coronavirus disease 2019 (COVID-19) outbreak, there has been an increase in hygiene practice, particularly hand washing and the use of hand sanitisers. These practices have undoubtedly assisted a great deal in combatting the rate of transmission and contributed immensely to saving lives. However, repeated hand washing and the use of sanitisers have both been linked with marked skin dryness and contact dermatitis. This especially holds true when the above-mentioned practices are carried out in the absence of intermittent hand moisturiser usage.

Effect of COVID-19 (SARS-CoV-2) Vaccination on Patients with Atopic Dermatitis Treated with Dupilumab: A Multicenter, Observational Study.

BACKGROUND: Atopic dermatitis (AD) patients usually wonder if their condition will worsen after vaccination or if they should continue with the treatment they are receiving. Considering that many patients treated with dupilumab had previously experienced severe AD symptoms and flares, the concerns are more understandable. OBJECTIVE: This study aimed to investigate the safety of the coronavirus disease 2019 (COVID-19) vaccination in patients with AD treated with dupilumab. METHODS: We enrolled 133 patients (101 dupilumab-treated and 32 systemic oral agents-treated as control group) with AD from six hospitals. Patients were asked about worsening pruritus and AD (5-point Likert scale) after vaccination. AD variables (eczema area and severity index [EASI], investigator's global assessment [IGA], itch numerical rating scale [NRS], sleep NRS, and patient-oriented eczema measure [POEM]) were compared pre- and post-vaccination. Adverse reactions to the COVID-19 vaccination were observed. RESULTS: The incidence of adverse reactions to COVID-19 vaccines and worsening AD symptoms in dupilumab-treated patients were not significantly different compared with that in the control group. The itch NRS score increased significantly after vaccination (p<0.001). However, there were no statistically significant differences between the pre-and post-EASI, IGA, and POEM scores. Eight patients (7.9%) had worse EASI scores and required rescue therapy; however, most were easily managed with low-dose steroids or topical agents. None of the patients discontinued dupilumab treatment. CONCLUSION: No serious adverse reactions were observed in patients with AD after COVID-19 vaccination. Exacerbation of pruritus and AD symptoms was observed but was mostly mild and transient.

The COVID-19 Pandemic and Recent Earthquake in Zagreb Together Significantly Increased the Disease Severity of Patients with Atopic Dermatitis.

BACKGROUND/OBJECTIVE: Stress may affect patients with atopic dermatitis (AD). The aim of this study was to examine the impact of the COVID-19 pandemic and the earthquake in Zagreb, Croatia (March 2020), on AD patients and their disease severity, symptoms/itch, and perceived stress. METHODS: Our observational cross-sectional study included three groups of AD patients diagnosed by a physician: group 1 (n = 50), who experienced both the pandemic (quarantine) and the earthquake; group 2 (n = 50), who experienced only the pandemic; and group 3 (n = 50), the comparison group, who experienced neither disaster (patients examined 2018-2019). Groups 1 and 2 were examined May-June 2020, immediately after the national lockdown/quarantine. Disease severity (SCORAD), data from the Perceived Stress Scale (PSS), and information on patients' confirmed allergies were recorded for all groups, while groups 1 and 2 additionally completed a questionnaire concerning their disease, hand hygiene, and experience during the pandemic and/or earthquake. RESULTS: The patients exposed to both disasters reported more pronounced AD worsening (p < 0.001; r = 0.388) and more frequent itching (p < 0.001; r = 0.350) than those exposed to the pandemic only. Notably, we found certain differences by gender: during the pandemic, women significantly more frequently washed their hands (81% of women washed "very frequently," while 52% of men washed "quite often") and had significantly higher PSS levels than men (p < 0.05). Concerning allergies, present or absent, during the pandemic, there was no significant difference in SCORAD between groups 1 and 2, neither when analyzed separately for indoor nor for outdoor allergens. The most commonly reported psychological disturbances during the pandemic were concern (46%), anger (18%), anxiety (16%), depression (9%), and increased alcohol, cigarette, and opioid agent use (6%). CONCLUSION: The COVID-19 pandemic together with the earthquake significantly increased disease severity and influenced AD worsening, itching, and psychological disturbances. This indicates that stressful events meaningfully affect the course of AD.

Occupational Skin Dermatitis among Healthcare Workers Associated with the COVID-19 Pandemic: A Review of the Literature.

The skin is the outermost layer of the human body and is continually exposed to numerous external stimuli, which can cause unwanted skin irritation. Occupational skin diseases are the most prevalent form of work-related illness and are found in a variety of sectors, particularly healthcare. During the recent COVID-19 pandemic, healthcare professionals experienced a variety of unexpected, unusual occupational skin diseases associated with COVID-19-engaged employment. Because the clinical characteristics of these types of skin inflammation are unique, this review focuses on the characteristics of a large category of occupational workers, namely COVID-19-engaged healthcare professionals. Furthermore, we examined the potential pathogeneses of occupational skin disorders associated with COVID-19-engaged labor, as well as different preventative methods.

Idiopathic Hypereosinophilic Syndrome Diagnosed in an Infant: A Case Report

Introduction: Idiopathic hypereosinophilic syndrome (IHES) is a rare disorder characterized by persistent eosinophilia (>1.5 x 109/L) for >=6 months, tissue infiltration with end-organ damage, and exclusion of known causes for hypereosinophilia. It is mainly observed in adults, and rarely in children. We report, to our knowledge, the first case report of IHES in an infant. Case Description: A 5-month-old male presented with severe failure to thrive and malnutrition. His hospitalization was complicated by acute kidney injury, pulmonary edema requiring intubation, pseudomonas bacteremia with concomitant tibial osteomyelitis, COVID-19 infection, and bradycardic arrest requiring CPR. Notably, patient had persistent eosinophilia (maximum 11.4 x 109/L) (Table 1). Parasite testing was negative. Immune work-up was normal (Table 1). Primary immunodeficiency panel testing of 407 geneswas negative. Endoscopy revealed eosinophilia in the sigmoid colon and rectum. Bone marrow biopsy revealed a low normocellular bone marrow (70%) with maturing trilineage hematopoiesis and increased eosinophils and eosinophil precursors (approximately 50% of nucleated cells). A FISH panel was negative for PDGRFRA/4q12, PDGRFRB/5q33, FGFR1/8p12, and ETV6/12p13 gene regions. The patient was diagnosed with IHES and started on steroids at 0.5 mg/kg/day. Hydroxyurea was added due to up-trending eosinophil count despite steroid therapy. Three months post-diagnosis, he is doing well off medications, with most recent eosinophil count being 2.1 x 109/L. Discussion(s): Hypereosinophilia in children is most commonly due to secondary causes such as atopic dermatitis, parasitic infections, neoplasms, graft-versus-host disease, sickle cell disease, and immunodeficiency. Once the above diagnoses have been excluded, IHES should be considered, especially in patients with evidence of end-organ damage. Copyright © 2022