It is crucial for pediatricians to maintain awareness of cutaneous signs and symptoms of systemic diseases to allow for prompt recognition and adequate management of such disorders in children.After completing this article, readers should be able to: Identify the classic dermatologic manifestations of common systemic diseases in children.Understand the epidemiology, etiology, and likely mechanisms of these dermatologic findings.Enlist the best diagnostic tests for quick and definitive diagnosis while minimizing risk to the patient.Outline the standard management approach for acute and long-term follow-up of these diseases.Coordinate an impactful multidisciplinary care approach and deliver appropriate education to the patient and family.The integument can serve as a diagnostic window to pathophysiologic changes of internal organ systems, offering timely and valuable clues to a systemic disease process. It is the largest organ of the human body, continuously regenerates, and is readily accessible for comprehensive examination. Systemic diseases influence multiple organs and often pose a diagnostic challenge due to their occult and/or diverse clinical presentations. Cutaneous features frequently serve as the initial or most prominent indicator of systemic disease, often allowing earlier diagnosis and intervention, eluding potentially debilitating complications of such illnesses. Furthermore, they might be the only markers of clinical disease in otherwise asymptomatic patients. (1)(2)(3)Several studies have estimated the prevalence of skin disease to be 15% to 20% in the general population; 12% of pediatric dermatology consultations are for diagnosis or management of systemic diseases. (4) Studies also note a considerable lack of confidence regarding recognition of dermatologic manifestations of systemic diseases among pediatricians and other primary care providers. Approximately 50% of patients referred to dermatologists by other medical providers receive a different diagnosis on evaluation. Access to dermatologic care can be challenging due to a maldistribution and undersupply of dermatologists in the United States. (5)(6) Thus, it is imperative for pediatric providers to maintain awareness of the cutaneous signs of particular systemic diseases to optimize patient care quality and effectively use available health-care resources. (4)(7)(8)(9)(10)The purpose of this review is to encapsulate the dermatologic manifestations of systemic diseases in childhood. Because this is a vast topic with a multitude of diseases to review, we include common, confusing, and timely (ie, multisystem inflammatory syndrome in children [MIS-C]) disorders only. Additional review articles focusing on specific subsets of cutaneous manifestations (eg, infection induced, connective tissue, nutritional, gastrointestinal, genetic) would be of value.The epidemiology, pathogenesis, diagnostic evaluation, and preferred management of each disease are reviewed based on the best medical literature to date. The diseases are arranged in alphabetical order, and a systematic approach to their dermatologic findings is summarized in Table 1.Acrodermatitis enteropathica (AE) is a rare disorder associated with zinc deficiency with an incidence of 1 in 500,000 children. (11) Most cases are caused by an autosomal recessive mutation in the gene encoding for zinc-ligand binding protein ZIP4 (zinc or iron regulator transporter-like protein), resulting in altered keratinocyte metabolism. The gene mutation is broadly distributed in the population such that inherited AE has no predilection for sex or race. Cases with a genetic etiology manifest early in infancy, characteristically days to weeks after weaning in breastfed infants. (12) A positive family history might be noted. (13) Patients can also develop AE from inadequate zinc intake (anorexia nervosa, bulimia nervosa, fad diet) or malabsorption (cystic fibrosis, inflammatory bowel disease, and excessive alcohol intake). (14)(15)(16)(17) Thus, it is imperative to consider this disorder in all pediatric patients based on history and demographics. The cutaneous manifestations are identical regardless of etiology. AE is characterized by periorificial dermatitis, alopecia, and diarrhea; however, this triad is present in only 20% of patients. (18)Patients initially present with symmetrical, erythematous to orange, scaly, crusted patches or plaques. Occasionally, vesicles or bullae can form. At first, perioral, anogenital, and acral areas are affected, but in the absence of adequate treatment, plaques erupt on the periorificial areas of the face (eyes, nostrils), abdomen, inguinal area, and thighs (Fig 1). Alopecia (typically diffuse), glossitis, gingivitis, stomatitis, onychodystrophy, and paronychia constitute additional mucocutaneous findings and usually indicate advanced disease. Superficial bacterial (commonly Staphylococcus aureus) and fungal (Candida albicans) infections are common and can mask the traditional signs of AE. Refractory diarrhea, failure to thrive, and neuropsychiatric features (irritability, anorexia, and depression) are common extracutaneous manifestations of AE and indicate prolonged deficiency. (14)(15)(16)(19)Diagnosis is based on physical examination findings and is confirmed with a serum zinc level of 50 µg/dL or less (≤7.65 µmol/L). Proper technique and equipment can reduce the potential risk of sample contamination in plasma zinc testing. (18) Low levels of serum alkaline phosphatase, a zinc-dependent enzyme, can also indicate the diagnosis. Some patients might have low serum albumin levels depending on etiology. (14)(15) Rapid clinical improvement after adequate zinc supplementation confirms the diagnosis of AE, especially in resource-limited areas. (20)Skin biopsy can be performed when the diagnosis is uncertain or an alternative diagnosis is suspected (which is typically diagnosed by pathologic confirmation). Histopathological analysis reveals necrosis of keratinocytes, cytoplasmic pallor, vacuolization, and confluent parakeratosis in the superficial layers of the epidermis. Psoriasiform hyperplasia occurs in resolving or chronic cases. (15)(21)Optimal management requires early diagnosis, zinc supplementation, and appropriate medical management and counseling based on patient needs (gastroenterology evaluation, dietary counseling, etc). Replacement therapy with 3 mg/kg per day of elemental zinc is recommended. Genetic deficiency will require lifelong supplementation, along with periodic monitoring of plasma zinc levels every 3 to 6 months. (15)(22) Nausea, vomiting, and gastric hemorrhage are well-known adverse effects of zinc therapy. Accidental overdose of zinc can prove fatal due to multiorgan failure. (23) A subset of patients with AE might benefit from genetic counseling.Dermatitis herpetiformis (DH) is a noninfectious autoimmune skin eruption due to gluten sensitivity. The misnomer alludes to the tendency of small blisters to appear in clusters, similar to a herpes simplex virus rash. (24)(25) Although gluten sensitivity is fairly common, DH is not consistently present such that the annual incidence rate is 0.4 to 3.5 per 100,000 people; only 4% of patients with DH are children and adolescents, with a slight male predominance. (26)(27)(28) Several studies demonstrate that carriers of human leukocyte antigens (HLAs) DQ2 and DQ8 exhibit a strong predisposition to DH. (29) The association of DH with gluten-sensitive enteropathy was first outlined in 1966, when it was described in relation to celiac disease. (30) Both of these entities share a unique tissue transglutaminase (TTG)–dependent immune response to gliadin peptides found in wheat, rye, and barley, with anti-TTG antibody–mediated immune complexes depositing in the dermis, subsequently allowing formation of blisters. (31) Several environmental factors also contribute to development or exacerbation of DH (amount of gluten ingested, intake of iodine-containing substances such as shellfish, and exposure to triiodomethane used in dental procedures). (32)(33)(34)(35)Patients typically present with clusters of erythematous papules and vesicles on the extensor surfaces of the elbows, forearms, back, buttocks, and knees (Fig 2). The rash is strikingly symmetrical in most patients. Less commonly, the scalp, face, and groin can also be involved. DH lesions are intensely pruritic; thus, the primary morphology is often replaced by excoriations and erosions. Oral manifestations are uncommon and include erythematous macules and erosions on the mucosa accompanied by a burning or sore sensation. Enamel defects along with delayed eruption of teeth can be present. (33)(36) Rarely, pediatric patients demonstrate palmoplantar purpura and petechiae. (37) Subclinical or mild gastrointestinal symptoms characteristic of celiac disease, such as abdominal bloating, cramps, diarrhea, or constipation, are evident in approximately 90% of patients with DH but frequently attributed to other factors. (38) DH can also manifest before onset of typical gastrointestinal manifestations of celiac disease. (39)(40) Patients with gluten-sensitive enteropathy have an increased risk of hypothyroidism, type I diabetes mellitus, and non-Hodgkin lymphoma. (38)After initial clinical suspicion, skin biopsy of an intact vesicle is conducted to confirm the diagnosis. Histopathologic analysis reveals neutrophilic infiltrate and fibrin deposition of the dermal papillae, with subepidermal blisters in mature lesions. These findings closely resemble other cutaneous blistering disorders, especially bullous pemphigoid and linear immunoglobulin A (IgA) bullous dermatosis, and should be differentiated accordingly. Clinical signs and symptoms can mimic urticaria, atopic dermatitis, and scabies. (36) The gold standard for diagnosis of DH is direct immunofluorescence of biopsy tissue, depicting IgA antibodies in the tips of dermal papillae and along the basement membrane of the perilesional skin. (38) Serologic testing provides further confirmation of DH and gluten-sensitive enteropathy, with IgA TTG antibodies and IgA endomysial antibodies being highly specific.Treatment of DH consists primarily of gluten avoidance and appropriate gastrointestinal evaluation. (41) A gluten-free diet often resolves the skin eruption. When additional treatment is required to achieve skin clearance, 0.5 to 2 mg/kg per day of dapsone given orally is suggested as the patient transitions to a gluten-free diet. Subsequently, it can be tapered off over 4 to 6 weeks and discontinued thereafter. If clinical improvement does not occur, dapsone can be given as an adjunct therapy. In addition, it can be reinstituted to manage severe recurrences of DH. Routine complete blood cell (CBC) counts, liver function tests, renal function tests, and screening for glucose-6-phosphate dehydrogenase deficiency is recommended before initiation of therapy. (42)Erythema nodosum (EN) is the most frequent form of panniculitis, a group of inflammatory disorders primarily involving subcutaneous fat. (43) It has a rare incidence before the second decade of life and is exceptional before 2 years of age. There is a familial predominance related to the presence of HLA haplotype (HLA-B8, HLA-A11, and HLA-B51) without any predilection for sex or race. (44)(45)(46)There is no identifiable underlying etiology in approximately 50% of patients. (47) The remainder seems to occur as a consequence of an infectious process, with β-hemolytic Streptococcus as the leading cause worldwide, followed by Mycobacterium tuberculosis in endemic areas. Rare cases due to other viral, bacterial, protozoal, and fungal infections have been reported. (44)(48) EN can also be a sign of inflammatory bowel disease, Behçet disease, and sarcoidosis, and it was recently reported in a 3-year-old girl with Kawasaki disease (KD). (45)(49) Other inciting factors, include pregnancy, underlying malignancy (consider the possibility if there is chronic recurrence or relapse despite an optimal treatment regimen), and medications (especially oral contraceptives and certain antibiotics). (50)(51)(52)(53)EN is characterized by the acute onset of symmetrical, tender, erythematous to violaceous, subcutaneous nodules. The anterior shin is the most common location, with the extensor surface of the forearms, trunk, and thighs occasionally involved (Figs 3 and 4). Rarely, unilateral disease has been documented. (54)(55) Nodules are characteristically round to oval, 1 to 5 cm in size, easily palpable, warm, and firm. Fluctuance and serous exudate can develop with time, along with coalescence to giant nodules. Nodules usually persist for 2 to 8 weeks and heal without scarring or ulceration. A bruise can remain, referred to as “erythema contusiformis,” but is an inconsistent finding. New outcroppings are expected and frequent, with cycles lasting up to 6 weeks. (50)(56)(57) A prodrome of low-grade fever, malaise, weight loss, arthralgia and cough may occur 1 to 3 weeks before disease onset. (58)Rare forms of EN include EN migrans and palmoplantar EN. The migrans variant is subacute, unilateral, and less painful, with a centrifugal distribution and central clearing. (59) Palmoplantar involvement is most common after exercise. All EN forms share similar histopathological features. (60)Diagnosis is usually clinical, with biopsy confirmation as needed. Histopathological analysis shows neutrophilic and lymphohistiocytic infiltration of the dermal adipose tissue, along with septal edema, radial granulomas (Miescher granulomas), and absence of true vasculitis. (61)(62) Laboratory investigation for an infectious etiology can be performed as needed (CBC count, rapid streptococcal antigen test, throat swab culture, antistreptolysin O titer, anti-DNAase, antihyaluronidase, Mantoux skin test, stool culture, and/or polymerase chain reaction assay), and suspect medications should be discontinued. A pregnancy test is recommended in postpubertal females. (45)(50)(63)The differential diagnosis of EN is broad and includes EN leprosum, child abuse, factitial disease, insect bites, Henoch-Schönlein purpura (HSP), urticaria, erythema induratum, fat necrosis, and cutaneous polyarteritis nodosa. (48)(64) Recurrences seldom occur but can be found in drug-induced cases of EN. (45)(59)Treatment is supportive with bed rest, leg elevation, and nonsteroidal anti-inflammatory drugs (except aspirin). In severe cases, systemic corticosteroids can be used. In addition, the underlying cause must be sought and if one is identified, must be managed accordingly. (44)(50) Oral dapsone, hydroxychloroquine, colchicine, potassium iodide, and topical heparin have been used as well. (65) Use of oral tetracycline has been suggested in refractory cases. (66)HSP, recently referred to as IgA vasculitis, is the most common systemic vasculitis in childhood. It has an incidence of 20 per 100,000 children, with most cases occurring between 4 and 6 years of age. (67)(68)(69) There is a slight male predominance; the disease is more prevalent in the Asian and white populations, especially in individuals of European descent. (70) The disease typically manifests in fall and winter, often preceded by an upper respiratory tract infection, commonly group A streptococcus. (71) Certain medications and insect bites are other possible inciting factors. Of note, no causal relationship has been established between vaccinations (eg, meningococcal vaccine and human papillomavirus vaccine) and vasculitides, including HSP. (72)(73) Clinical findings similar to HSP have been found in conjunction with familial Mediterranean fever as well. (74)HSP is an immune-mediated inflammatory disease characterized by IgA1-containing immune complexes inside the walls of small vessels of affected organs, including the kidneys, skin, joints, and small intestine. (75)The hallmark clinical features are palpable purpura (in the absence of thrombocytopenia or coagulopathy), arthritis/arthralgias, and abdominal pain along with varying degrees of proteinuria, microscopic or macroscopic hematuria, and sometimes hypertension. Typically, skin and joint findings are the earliest signs. Cutaneous manifestations include erythematous, asymptomatic edematous papules and urticarial wheals distributed bilaterally over pressure-dependent areas, such as the lower limbs, buttocks, and belt line (Figs 5 and 6). The face, trunk, and forearms can be involved at any age but are more commonly seen in infants and nonambulatory children. The lesions are well-defined and tend to occur in “crops.” Eventually they coalesce to form ecchymoses. Palpable purpura less than 10 mm in diameter is a pathognomic feature of HSP; however, the literature does report cases without palpable lesions. Eruptions last for up to 10 days and self-resolve without residual scars. A brown discoloration might be present on resolution, which can take days to weeks to fade. Localized, subcutaneous, nonpitting edema over the dorsal surfaces of the hands, ankles, and feet is present in 50% of patients. Pitting edema secondary to kidney disease or severe protein-losing enteropathy can accelerate these findings. Blistering eruptions, koebnerization, and capillary fragility can occur. (76)(77)(78)(79)(80) Skin biopsy shows leukocytoclastic vasculitis with IgA-predominant immune complex deposition in postcapillary venules, arterioles, and capillaries. (81)Diagnosis is typically clinical, with renal and/or skin biopsy conducted in unusual cases. Consensus criteria developed in 2005 identify cutaneous findings without thrombocytopenia or coagulopathy as a mandatory criterion for HSP in pediatric patients, along with 1 or more of the following: abdominal pain, joint findings, renal disease, leukocytoclastic vasculitis, or membranoproliferative glomerulonephritis with IgA deposition. (82)Differential diagnosis includes cutaneous small vessel vasculitis, acute hemorrhagic edema of infancy, microscopic polyangiitis, KD, Rocky Mountain spotted fever, and bacterial endocarditis. (69)(77)Treatment is supportive with optimal hydration, pain control, bed rest, elevation of extremities, and periodic surveillance for development of any complications. Corticosteroids are used in severe cases. Most children undergo complete resolution within 4 weeks without long-term sequelae. Recurrence is commonly associated with HSP nephritis. Follow-up visits with urinalysis and blood pressure measurements are generally recommended weekly or biweekly for the first 2 months, followed by every other month for the first year after initial presentation once the disease seems to be subsiding. Any concerning test results should be evaluated with a serum creatinine level. For persistent hypertension, proteinuria, or renal insufficiency, referral to a pediatric nephrologist is reasonable. (78)(79)(83)(84)Inflammatory bowel disease (IBD), a unique combination of Crohn’s disease and ulcerative colitis, is an immune-mediated systemic inflammatory disorder triggered by changes in the gut microbiota and certain environmental factors in genetically predisposed individuals. Approximately 5% to 25% of cases occur in the pediatric population, with a slight male predominance and often a strong family history. (85)(86)(87)(88)(89)(90)Typically, diarrhea (bloody or nonbloody), abdominal pain, growth failure, delayed puberty, and systemic symptoms (fever, fatigue) raise concern for IBD. However, extraintestinal manifestations can develop before IBD diagnosis or during management of known disease. (91)(92)(93) Approximately 15% of extraintestinal manifestations are cutaneous. (94)EN is the most common dermatologic finding, with a prevalence of 8% in Crohn’s disease and 3% in ulcerative colitis. EN induced by IBD rarely occurs before gastrointestinal symptom onset, parallels underlying intestinal activity, and lasts for 3 to 6 weeks. Such cases are usually a single episodic cycle when the underlying intestinal disease is treated and monitored adequately. (91)(95)(96)(97)The second most common cutaneous finding in IBD is pyoderma gangrenosum (PG). Approximately 4% of cases occur in children, with a mean age at onset of 14 years. Cases in infancy have been reported. (98)(99) PG exhibits a female predominance and is more commonly associated with ulcerative colitis. Initially, an erythematous, painful papule or pustule forms, rapidly evolving into a violaceous, deep ulcer with a rolled border. The leg is a common site, in addition to a stoma site, if present. Progression leads to an atrophic, cribriform scar. PG lesions show varying morphology over time, denoted as pustular, ulcerative, bullous, and vegetative subtypes. PG can erupt due to pathergy, such that the head and perineal area are affected, particularly in young children. Pathergy refers to altered tissue reactivity that occurs in response to minimal trauma. (100) Histopathology exhibits sterile neutrophilic inflammatory dermatoses in the dermis and subcutaneous tissue. Treatment regimens are many, including corticosteroids, tacrolimus, and tumor necrosis factor (TNF) antagonists. Mechanical trauma must be avoided along with appropriate wound care. In case of peristomal PG, dermatologists and skilled ostomy nurses should be consulted. The disease course lasts several months, with recurrence in 25% of patients. As with EN, underlying gastrointestinal disease control is imperative. Immunologic disorders such as IgA gammopathy, human immunodeficiency virus, and leukemia can also manifest PG and must be excluded. (91)(95)(96)(101)(102)Genital edema might be the only presenting sign of IBD and usually involves prominent genital swelling (Fig 7). Erythema and erosions can be present. Genital signs are typically bilateral, although unilateral disease can occur and includes erythema, swelling, and erosions of the perianal area (Fig 8), perineum, penis, scrotum, clitoris, labia, and vulva. Warty plaques or a pedunculated mass can form with disease progression. (103)Oral lesions are common in IBD and can manifest before gastrointestinal symptoms in approximately 50% of patients, including the pediatric population (Fig 9). (104)(105) Aphthous stomatitis, especially if recurrent and extensive, tends to manifest frequently with Crohn’s disease. (106) Affected oral mucosa exhibits nodular granulomatous swelling with a characteristic cobblestone appearance and mucosal tags. In addition, orofacial granulomatosis, a chronic or refractory swelling of oral mucosa with characteristic histologic features of noncaseating granulomas, can be found in conjunction with Crohn’s disease. (107) Pyodermatitis-pyostomatitis vegetans describes a combination of pustular and vegetating plaques affecting the skin and oral mucosa simultaneously or consecutively. Sometimes genital areas become affected as well. Pyodermatitis-pyostomatitis vegetans occurs frequently with ulcerative colitis and usually responds well to corticosteroids and azathioprine. (108)(109) Therefore, children with unexplained or persistent oral mucosal lesions should undergo a detailed oral as well as genital and rectal examination, along with appropriate blood tests (CBC count, iron levels, erythrocyte sedimentation rate) and biopsy procedures (if needed), to rule out the possibility of underlying IBD. (107)Metastatic Crohn disease, a form of granulomatous dermatitis, is a rare finding in pediatric patients with Crohn disease. It comprises erythematous, violaceous plaques, abscess, swelling, and ulcerating nodules and fissures, often in a knifelike pattern on the lower extremities and intertriginous areas. Bowel management with corticosteroids, immunosuppressive agents (eg, azathioprine, cyclosporine), and TNF antagonists is the mainstay of treatment. (110)(111)On rare instances, pediatric patients with IBD can develop hidradenitis suppurativa, a chronic, recurrent inflammatory disorder of hair follicles mainly involving sites with apocrine glands, including the axillae and the inguinal and perianal areas. (112)Psoriasis is more common in patients with IBD than in the general population. In addition, psoriasiform dermatitis is common in IBD as an adverse effect of anti-TNF treatment (known as “paradoxical reaction”). This is particularly curious because anti-TNF treatment is also used to successfully manage refractory generalized psoriasis. As such, psoriasiform skin eruptions along the extensor surfaces of the forearms, scalp, face, trunk, knees, and joint flexures in patients with IBD should be investigated by a dermatologist for etiologic clarification and treatment suggestions, as anti-TNF medication-induced skin disease can necessitate changing systemic medications. Having to change medications can be disappointing if the bowel disease is under good control. (113)Distinct nutritional dermatoses can occur in IBD secondary to deficiency of vitamins (A, C, E, K, and B12) and essential trace elements (zinc). (96) Cutaneous small vessel vasculitis, polyarteritis nodosa, epidermolysis bullosa, and alopecia have also been observed. (111)Juvenile dermatomyositis (JDM) is the most frequent form of childhood idiopathic inflammatory myopathy, with an annual incidence of 2 to 4 cases per 1 million children. (67)(114) The mean age at onset is 5 to 10 years, with a female-to-male ratio of 2:1. (115) Certain alleles, including HLA 8.1 ancestral haplotype (AH8.1), HLA-DRB1*3:01, and TNF-α-308A, have been associated with an increased risk of JDM. (116)(117) It has also been observed in response to an underlying infectious process, mainly of respiratory or gastrointestinal origin. (118)JDM is a systemic vasculopathy primarily involving both muscle and skin; however, skin-limited disease is also common (eg, dermatomyositis sine myositis). A heliotrope rash is a discrete, red-purple macular rash located over the upper eyelids; it can involve the nose, malar area, and upper lip as well. Another hallmark feature is Gottron papules (Fig 10), which are erythematous to violaceous papulosquamous lesions generally located over the dorsal surface of the metacarpophalangeal and interphalangeal joints; they can also involve the extensor surfaces of the elbows, knees, and medial malleoli. Secondary changes such as scale, crust, erosion, ulceration, telangiectasia, and hypopigmentation or hyperpigmentation can develop in later stages of the disease. In dark-skinned individuals, hyperpigmentation can mask underlying erythema such that the lesions must be palpated to confirm blanchable erythema. The Gottron sign is the presence of flat erythematous to violaceous lesions with a similar distribution and clinical course as Gottron papules. Macular erythema in discrete or confluent distribution can manifest over the upper anterior chest and anterior neck, called the “V-sign.” The “Shawl sign,” a less frequent cutaneous eruption, is a macular erythematous rash located over the posterior neck, upper arm, and lateral arms (similar to a shawl distribution). Cutaneous features of JDM often develop before muscle weakness but can manifest concurrently as well. Exposure to sunlight, especially to ultraviolet light radiation, exacerbates skin findings of JDM. (119)(120)(121) Patients can also develop focal patches of nonscarring alopecia, erythema, and inflammation on the scalp (Fig 11). (122) Subcutaneous calcification and ulceration of overlying skin can develop in chronic, often untreated, cases of JDM. (123) Nail fold capillary dilatation, loss of capillaries, and distinct branching capillary loops (bushy loops) can also be present, causing roughened cuticles. (124)(125)Symmetrical proximal muscle weakness is an integral component of JDM. Functional limitations increase as the disease progresses. Children are often fatigued and experience an intermittent low-grade fever. Acanthosis nigricans along with insulin resistance and type 2 diabetes mellitus can develop as well. (126)Histopathological analysis of muscle tissue reveals a perivascular inflammatory infiltrate, necrosis of fibers, endothelial thickening, reduced capillary density, and an exaggerated activity of major histocompatibility complex class I molecules. Skin biopsy can reveal similar vascular changes, perivascular inflammatory infiltrate, vacuolar interface changes of the basal keratinocytes, dermal mucin, and occasional vascular fibrin thrombi. (119)(120)In 2017, the European League Against Rheumatism/American College of Rheumatology revised and formulated criteria for the diagnosis of adult and pediatric idiopathic inflammatory myopathies with and without invasive tests (eg, muscle biopsy). (114) After initial clinical suspicion, serum levels of muscle enzymes indicative of muscle damage and inflammation (creatine kinase, lactate dehydrogenase) and inflammation (C-reactive protein, erythrocyte sedimentation rate) are typically ascertained. (127)(128)(129) Measurement of myositis-specific autoantibodies, magnetic resonance imaging, electromyography, and muscle biopsy can be performed in atypical cases. (130)Initial treatment involves high-dose oral prednisolone (2 mg/kg per day) with methotrexate (15 mg/m2, subcutaneous injection) and folic acid. (131) In severe cases, intravenous methylprednisolone or intravenous cyclophosphamide can be used. Intravenous immunoglobulin (IVIg) is used in refractory cases. Mycophenolate mofetil, tacrolimus, hydroxychloroquine, rituximab, and anti-TNF agents have also been used. Physical and occupational therapy, sunscreen, and adequate psychosocial support are vital for successful management of JDM. (127)(132) Skin-limited disease, or skin involvement persisting despite systemic treatment, is improved by topical corticosteroids and calcineurin inhibitors. (133)(134)(135)Langerhans cell histiocytosis (LCH) describes a clonal proliferation and infiltration of myeloid progenitor cells (Langerhans cells) into multiple organs, resulting in infla