Life-threatening pediatric dermatoses, while rare, can be particularly devastating for patients. Clinicians are often lulled by the benignity of most childhood disorders. However, without a vigilant index of suspicion, many potentially morbid conditions may be discovered too late for appropriate management. This article will review the presentation, treatment, and prognosis of several of the more common and more destructive dermatoses seen in children and adolescents. They are toxic epidermal necrolysis (TEN), staphylococcal scalded skin syndrome (SSSS), Kawasaki’s Disease (KD), hemangiomas of the head and neck, pediatric melanoma, and Langerhans’ cell histiocytosis (LCH). These conditions range in origin from the inflammatory to the infectious to the neoplastic and comprise the “Big 6” that dermatologists should strive to recognize early in their presentation.
1. SJS/TEN
Perhaps the most life-threatening and rapidly progressive emergency in pediatric dermatology is the spectrum of disease encompassing Stevens Johnson syndrome and toxic epidermal necrolysis. These two entities are characterized by widespread erythematous, edematous plaques with prominent mucosal involvement. Nearly all cases of TEN and SJS are medication-induced and overall mortality may approach 40%. This spectrum is one of the few dermatologic conditions where full-thickness epidermal necrosis is observed.
What causes it? The pathogenesis of SJS/TEN is poorly understood, however, there appears to be some genetic component, because first-degree relatives may be similarly affected when exposed to an offending medication such as sulfa derivative.
The accumulation of toxic metabolites from these agents may be responsible for cell apoptosis and the onset of disease. Some studies suggest that the inappropriate release of perforins may be responsible for unmediated keratinocyte death. There is more recent, convincing data to suggest that a cell-surface “death receptor” (Fas) and an increase in its triggering ligand (FasL) may be responsible for the onset of disease. IVIG therapy is specifically designed to block this interaction and will be discussed later in more detail as a therapeutic option.
The incidence of SJS/TEN is rare, ranging from 0.5 to 1.2 per million per population year. The direct cause of death among those patients with poor outcomes is sepsis (owing to a compromised epidermal barrier) and respiratory distress. Prognostic factors include high body surface area (BSA) involvement, hypoalbunemia (<2 g/dl), greater than 5 days of neutropenia, and persistent azotemia.
Children who do well normally re-epithelialize within 3 weeks.
* The most serious long-term sequelae for survivors of SJS/TEN involve the eye, with conjunctival erosions and cicatrisation accounting for significant morbidity in up to 40% of children. No gender predilection exists for pediatric SJS/TEN, and the condition may occur at any age.
The presentation of SJS typically begins with constitutional symptoms a few days prior to any cutaneous lesion. Itching of the conjunctiva or photophobia may be an early symptom.
Early skin lesions are poorly defined edematous plaques with dusky or purpuric centers. A careful medication history will usually reveal the offending agent. Sulfonamide antibiotics are the most commonly implicated, but case reports exist for an innumerable number of pharmacologic incitors.
Flaccid bullae, where present, arise once epidermal necrosis sets in. Acral involvement is also common. Internal involvement most commonly includes the gastrointestinal and respiratory systems and can be devastating.
The differential diagnosis for SJS/TEN is somewhat limited owing in large part to its unmistakable fulminant presentation. Graft versus host disease and staphylococcal or streptococcal scalded skin syndrome may mimic SJS/TEN focally, but the latter do not exhibit full thickness sloughing and prominent mucosal involvement.
The work-up for suspected SJS/TEN should include a complete blood cell count, SMA20, and coagulation profile to rule out emerging disseminated intravascular coagulation (DIC). Cultures of denuded skin and blood are also important to assess for any superinfection and possible sepsis. A baseline A/P chest film should be obtained as tracheo-bronchial involvement is a dreaded complication. A snap frozen section of denuded skin taken from the bedside can clinch a diagnosis of SJS/TEN within minutes.
Treatment of SJS/TEN is decidedly controversial. One thing is certain: stop the offending medication. A multidisciplinary approach within a burn unit setting is highly recommended. Aggressive fluid and electrolyte replacement should be initiated early. Consults to pulmonary, gastrointestinal, and ophthalmology specialists are a must. A plastic surgeon may be very helpful with woundcare techniques to minimize additional skin trauma.
While the role of intravenous corticosteroids is still unclear, convincing studies advocate against their use because of higher mortality rates secondary to overwhelming sepsis. In smaller studies, intravenous immune globulin (IVIG) has proven very useful for SJS/TEN with halting of disease progression seen over 48 hours and a survival rate of 90%.
Cyclosporin, cyclophosphamide, and various monoclonal antibodies have met with varied success in uncontrolled clinical studies and are currently not recommended for use in children with SJS/TEN.
2. Staphylococcus-Scalded Skin Syndrome (SSSS)
SSSS is a toxin-mediated exfoliative dermatitis caused by phagogenic toxins released by Staphylococcus aureus or streptococcocal strains. These toxins create intraepidermal bullae by cleaving desmoglein 1, a cadherin that facilitates cell-to-cell cohesion of keratinocytes within the granular layer. Only about 5% of staph and strep isolates are capable of producing these protease toxins and inducing SSSS.
* While children with SSSS generally do well after antibiotic treatment, a mortality rate of 4% exists for those cases misdiagnosed or discovered late.
The presentation of SSSS. The root of original infection is typically found in the nasopharynx or in the skin as a simple impetigo. SSSS most commonly affects children younger than 5 years, often neonates, primarily because renal immaturity prevents adequate clearance of toxin. For this reason, older children with renal impairment may be at a significantly increased risk of developing SSSS.
What causes it? SSSS begins with constitutional symptoms, followed in a few days by orange-red patches that are acutely tender. Periorificial and flexural prominence is common with a progression from plaques to blisters within 48 hours. These blisters are toxin-mediated and therefore sterile. Culturing these bullae is unhelpful in clinching a diagnosis of SSSS.
The differential diagnosis of SSSS may include TEN and Kawasaki’s Disease, therefore, work-up for this condition should include epidermal frozen section. A targeted multi-culture of the nasopharynx, anus, and axilla is advised where frank cutaneous infection is not evident.
Treatment of SSSS is a straight-forward targeting of the infectious focus. This generally requires a penicillinase-resistant penicillin (such as dicloxacillin) or cephalosporin. There is some evidence to suggest that clindamycin, in addition to being anti-staphylococcal, may also decrease the release of proteolytic toxins. For this reason, I use clindamycin as first line for my children who present with SSSS.
Aggressive replenishment of fluid and electrolytes is important where a disrupted barrier may result in imbalance. Treatment of potential contacts, such as neonatal nurses and parents, with topical mupirocin is recommended to reduce colonization and recurrent infection.
3. Kawasaki’s Disease (KD)
Kawasaki’s Disease (KD) is a systemic, idiopathic vasculitis that is the most common cause of acquired cardiac disease. No infectious etiology has as of yet been confirmed for KD and the condition is particularly challenging to physicians because there is no definitive testing available for its diagnosis.
Children with major histocompatibility complexes (MHC) Bw22 and Bw22J2 are more commonly affected.
Presentation of KD is most common in boys under the age of 5 years.
The acute phase begins with LAD and fever and is followed by acral desquamation and edema. While the rash of KD is classically perineal, this exanthem is exceptionally polymorphic and may present in any form. Rash of some sort is seen in more than 90% of patients.
Non-exudative, conjunctival injection is also seen in 90% of patients, often accompanied by an anterior uveitis. Other characteristic physical findings include dry, fissured lips (80%), strawberry tongue (50%), and massive cervical lymphadenopathy (70%).
Systemic features that are variably present weeks to months after acute illness include sterile pyuria, aseptic meningitis, and testicular swelling.
Erythrocyte sedimentation rate and C-reactive protein levels, while non-specific, are both extremely elevated during the acute and subacute phases. Thrombocytosis is also prevalent and platelets may remain elevated for up to 4 weeks following defervescence.
Arthralgias and coronary aneurysm leading to sudden death are most common during the subacute phase and their emergence should be anticipated. Laboratory evaluation of KD should also include a CBC (for leukocytosis, thrombocytosis and anemia), serum chemistry (for evidence of transaminitis), and a urinalysis (for sterile pyuria). An immunoglobulin profile exhibiting elevated IgM, IgA and IgE may offer lend support to the diagnosis. A baseline EKG will reveal nonspecific abnormal findings (ST changes, prolonged PR segment), while echocardiography will exhibit any anuerysmal changes present. Clinicians must remember to repeat an echo 1 month and 3 months following acute illness, because aneurysms may develop late in a child’s disease course.
The most feared sequelae seen with KD is coronary aneurysm that may be seen in 20% to 25% of untreated children. Appropriate therapy within 10 days of onset of illness reduces this risk to about 3%. Aneurysms may be seen months after acute disease onset and prompt diagnosis by way of echocardiography is essential.
Risk factors of coronary aneurysm include male sex, pre-existing cardiac disease, prolonged illness, age <1 year, recurrence of fever after initial defervesence, and anemia with hypoalbunemia at initial visit.
Cardiology and infectious disease consults will often prove helpful in confirming a suspected case of KD.
The criteria for diagnosis of KD are: fever of unknown origin (FUO) for more than 5 days, generalized erythema and desquamation, cervical lymphadenopathy, conjunctival injection, and edema of both hands and feet.
The differential diagnosis for KD is broad because these children may have such a nonspecific presentation. Conditions that may masquerade as KD include drug eruptions, SSSS, SJS/TEN, Rocky Mountain Spotted Fever, and a host of nonspecific viral exanthems. In my practice, any child with unexplained fever, LAD, and an atypical exanthem with pedal edema will receive a Kawasaki work-up.
Treatment of KD centers upon reducing inflammation of the myocardium and coronary artery wall. Recommended therapy for KD includes IVIG as a single infusion (or once daily for 3 days) and high-dose aspirin that is tapered over 6 to 8 weeks. Smaller coronary aneurysms may regress over 2 years, while those >8 mm carry a lifetime risk of stenosis and resultant ischemic heart disease.
4. Hemangiomas of the Head and Neck
Hemangiomas of infancy (HOI) are the most common benign tumors of infancy, affecting 2% of newborn healthy infants. The vast majority of these lesions appear within the first few weeks of life and grow rapidly only to spontaneously regress before early childhood. Hemangiomas are observed more commonly in female infants and those born prematurely, occurring in a quarter of infants weighing under 1000 g. There is also a markedly higher incidence in babies born to mothers who have underwent chorionic villus sampling, a fascinating statistic that is likely related to this lesion’s poorly understood pathogenesis.
HOI classically present a few weeks after birth as bright red, occasionally telangiectatic, soft, compressible nodules or tumors. They are most commonly found on the head and neck where they pose special concerns to the treating dermatologist.
Large facial hemangiomas may be seen in association with PHACES Syndrome:
• consisting of Posterior fossa (intracranial) abnormalities
• large facial Hemangiomas
• Arterial abnormalities (i.e. aortic coarctation)
• Cardiac defects (such as atrial or ventricular septal defects)
• Eye findings (i.e. cataracts)
• Sternal defects (i.e. raphe or agenesis).
These findings are rarely found all together, therefore, the presence of a large facial hemangioma should trigger imaging of the central nervous system (CNS), consultation with an ophthalmologist, and an echocardiogram to rule out associated defects.
When a large hemangioma is found in the neck region, special consideration should be given to the possibility of laryngeal/airway involvement. While an infant may not exhibit symptoms of stridor at birth, the expected rapid proliferation of a hemangioma can result in life-threatening airway compromise very quickly.
Any infant with a mid- to large-sized hemangioma should receive an evaluation from a pediatric ENT colleague for laryngoscopic evaluation.
Smaller hemangiomas of the face are also of grave concern when found periocularly. Visual pathways are formed early in infancy and any obstruction of the visual axis can potentially lead to irreversible hemi-neglect. Evalu-ation by a pediatric ophthalmologist is usually sufficient to assess for axis obstruction, and occasionally the unaffected eye may be patched for a short time. An MR of the orbits is occasionally also required to rule out intro-orbital extension.
Treatment of hemangiomas of the head and neck that meet any of the above criteria is recommended but varies greatly depending on an infant’s age, size of the lesion, the presence of ulceration, and any immediate threat to systemic function. Even lesions of the head and neck that do not cause systemic compromise may qualify for treatment where the potential for ulceration and scar formation is great.
Smaller hemangiomas may be amenable to intralesional corticosteroid injection, although dermatologists should refrain from treating lesions abutting the orbital rim to avoid the low but appreciable risk of ophthalmic arterial embolus.
For larger HOI, most pediatric dermatologists will begin with high-dose oral prednisone in dosages ranging from 2 to 4 mg/kg/d usually for several months followed by a slow taper. Ideally, oral corticosteroids will slow, and in some cases reverse, hemangioma proliferation, however, the potential risks of corticosteroids in an infant must be weighed against their benefit.
Adjunctively, treatment with the pulsed-dye laser (585 or 595nm) may be exceptionally helpful in both lightening and slowing proliferative lesions. Where possible without grave surgical morbitity, excision may also be considered for smaller hemangiomas.
5. Melanoma (MM)
Malignant melanoma (MM) is thankfully an exceedingly rare phenomenon in the pediatric population. Nonetheless, several cases have been reported in children and it is vital that clinicians remain vigilant in assessing atypical looking nevi in patients under 18. Malignant melanoma is not only confined to children who have congenital photosensitivity disorders such as xeroderma pigmentosa and basal cell nevus syndrome.
About 2% of melanomas occur in patients under 18 and only one-quarter of these arise in pre-adolescents. Overall incidence of melanoma is increasing in the United States; currently melanoma represents 3% of all pediatric malignancies. While some mild gender predilection may exist for females, MM is generally believed to affect both sexes equally.
Clinical detection of melanoma in children is similar to that in adults, although there is some evidence to suggest that the often relied upon ABCD criteria may be even more fallible in the pediatric population. For now, this system coupled with dermoscopy is the best we have for the clinical detection.
Any lesion that is asymmetric, exhibits an irregular border, contains variegated color (greater than 3), or grows rapidly in size should be biopsied for histologic evaluation. Likewise, any symptomatic lesion (itching, pain) should be sampled.
The two most common presentations for childhood melanoma are either a rapidly growing lesion (either acquired or congenital) or a “pyogenic granuloma” type lesion that may appear red, amelanotic and friable. In my experience, patients with chromosomal abnormalities, such as Down Syndrome, should be considered a special class with an slightly increased risk of malignant lesions.
Melanoma arising out of a congenital lesion is a controversial topic and warrants special consideration. Small- and medium-sized (up to 20 cm in a child) congenital melanocytic nevi are exceptionally common and probably carry a lifetime risk of malignancy of well under 1%.
Current estimates for malignancy arising in a giant congenital melanocytic nevus (GCN) are also disparate but generally fall between 1% and 3% with a few notable estimates that lie much higher. When malignancy does arise from a GCN, it typically does so within the first decade of life. While some authors suggest prophylactic removal of any GCN early in life, even extensive excisions cannot protect against melanoma development deep within facial planes.
Treatment consisting of excision of atypical or “dysplastic” nevi, whether congenital or acquired, is standard of care for the prevention of malignant deterioration. The vast majority of these procedures result in definitive prevention with a near zero risk of recurrence.
Pediatric melanoma usually presents deeper and with a poorer prognosis than its adult counterpart, most likely because of a delay in diagnosis.
When deeper (i.e. >1 mm) melanomas are discovered, sentinel lymph node biopsy is a minimally invasive procedure that is helpful in identifying metastasis-in-transit.
Where involvement of a lymphatic basin is identified, removing nodes and enrolling the patient in one of several experimental protocols such as interferon is customary.
Children with a previous diagnosis of severely dysplastic nevi or melanoma are at a far greater risk of a second malignant lesion and should be followed closely for the development of additional lesions.
6. Langerhans’ Cell Histiocytosis (LCH)
Langerhans’ cell histiocytosis (LCH) is a group of disorders characterized by the idiopathic proliferation of specialized lymphocytes, called Langherhans cells. These dendritic cells provide immune system surveillance within the epidermis. An uncontrolled dissemination of this cell subset may result in fulminant organ failure (previously termed Letterer-Siwe) or a solitary indolent lesion (previously termed eosinophilic granuloma). Whether this proliferation is neoplastic or reactive is unknown.
LCH is rare, affecting 1 to 5 people per million per year. The local form of LCH, while indolent, is not life-threatening.
The disseminated form of LCH is rapidly lethal in 50% of infants under the age of 2 years.
The disease presents with symptoms that may mimic systemic malignancy with fever, anemia and hepato-splenomegaly.
Cutaneous lesions are often a promontory sign of LCH and consist of eroded, crusted papules in a perioraficial, predominantly perineum and perioral, location.
LCH may be painless or may result in significant pain if bony involvement is present. LCH with bone involvement can have morbid mass effects, such as fractures, propotosis and pituitary dysfunction, when bony lesions affect adjacent parenchyma. After bone, lymph node, spleen, and liver involvement are most common.
The differential diagnosis of LCH includes seborrheic dermatitis and erythema toxicum neonatorum. LCH may be best differentiated from these more common entities by its failure to respond to traditional therapy.
The work-up of LCH requires a CBC and, in the case of pancytopenia, a bone marrow aspirate to evaluate for skeletal involvement. Liver function enzymes should be assessed and, in the case of transaminitis, a liver biopsy should be performed to assess the extent of liver involvement. As the sella tursica is commonly involved, a urine osmolarity may be helpful to screen for diabetes insipidus. A chest X-ray and skeletal survey is recommended where systemic LCH is suspected. In cases of severe dissemination, a MR image of the CNS should be considered to evaluate for cerebral involvement. A skin biopsy is exceptionally helpful in arriving at a diagnosis of LCH.
The treatment of LCH is determined in large part by extent of disease. Mild forms do not require treatment at all, while multicentric LCH with organ involvement may be treated with systemic steroids or in some cases targeted radiation. Mild skin only involvement may be treated with topical steroids, while moderate to severe skin only disease may benefit from PUVA or topical nitrogen mustard (20%).
Recognizing the “Big 6”
Thankfully, the vast majority of pediatric dermatoses are non-threatening, however, clinicians should be aware of those conditions that when caught early may be treated successfully without permanent morbidity. The “Big 6” conditions discussed above are conditions that can be recognized and treated early in their course to avoid a poor prognosis.
Life-threatening pediatric dermatoses, while rare, can be particularly devastating for patients. Clinicians are often lulled by the benignity of most childhood disorders. However, without a vigilant index of suspicion, many potentially morbid conditions may be discovered too late for appropriate management. This article will review the presentation, treatment, and prognosis of several of the more common and more destructive dermatoses seen in children and adolescents. They are toxic epidermal necrolysis (TEN), staphylococcal scalded skin syndrome (SSSS), Kawasaki’s Disease (KD), hemangiomas of the head and neck, pediatric melanoma, and Langerhans’ cell histiocytosis (LCH). These conditions range in origin from the inflammatory to the infectious to the neoplastic and comprise the “Big 6” that dermatologists should strive to recognize early in their presentation.
1. SJS/TEN
Perhaps the most life-threatening and rapidly progressive emergency in pediatric dermatology is the spectrum of disease encompassing Stevens Johnson syndrome and toxic epidermal necrolysis. These two entities are characterized by widespread erythematous, edematous plaques with prominent mucosal involvement. Nearly all cases of TEN and SJS are medication-induced and overall mortality may approach 40%. This spectrum is one of the few dermatologic conditions where full-thickness epidermal necrosis is observed.
What causes it? The pathogenesis of SJS/TEN is poorly understood, however, there appears to be some genetic component, because first-degree relatives may be similarly affected when exposed to an offending medication such as sulfa derivative.
The accumulation of toxic metabolites from these agents may be responsible for cell apoptosis and the onset of disease. Some studies suggest that the inappropriate release of perforins may be responsible for unmediated keratinocyte death. There is more recent, convincing data to suggest that a cell-surface “death receptor” (Fas) and an increase in its triggering ligand (FasL) may be responsible for the onset of disease. IVIG therapy is specifically designed to block this interaction and will be discussed later in more detail as a therapeutic option.
The incidence of SJS/TEN is rare, ranging from 0.5 to 1.2 per million per population year. The direct cause of death among those patients with poor outcomes is sepsis (owing to a compromised epidermal barrier) and respiratory distress. Prognostic factors include high body surface area (BSA) involvement, hypoalbunemia (<2 g/dl), greater than 5 days of neutropenia, and persistent azotemia.
Children who do well normally re-epithelialize within 3 weeks.
* The most serious long-term sequelae for survivors of SJS/TEN involve the eye, with conjunctival erosions and cicatrisation accounting for significant morbidity in up to 40% of children. No gender predilection exists for pediatric SJS/TEN, and the condition may occur at any age.
The presentation of SJS typically begins with constitutional symptoms a few days prior to any cutaneous lesion. Itching of the conjunctiva or photophobia may be an early symptom.
Early skin lesions are poorly defined edematous plaques with dusky or purpuric centers. A careful medication history will usually reveal the offending agent. Sulfonamide antibiotics are the most commonly implicated, but case reports exist for an innumerable number of pharmacologic incitors.
Flaccid bullae, where present, arise once epidermal necrosis sets in. Acral involvement is also common. Internal involvement most commonly includes the gastrointestinal and respiratory systems and can be devastating.
The differential diagnosis for SJS/TEN is somewhat limited owing in large part to its unmistakable fulminant presentation. Graft versus host disease and staphylococcal or streptococcal scalded skin syndrome may mimic SJS/TEN focally, but the latter do not exhibit full thickness sloughing and prominent mucosal involvement.
The work-up for suspected SJS/TEN should include a complete blood cell count, SMA20, and coagulation profile to rule out emerging disseminated intravascular coagulation (DIC). Cultures of denuded skin and blood are also important to assess for any superinfection and possible sepsis. A baseline A/P chest film should be obtained as tracheo-bronchial involvement is a dreaded complication. A snap frozen section of denuded skin taken from the bedside can clinch a diagnosis of SJS/TEN within minutes.
Treatment of SJS/TEN is decidedly controversial. One thing is certain: stop the offending medication. A multidisciplinary approach within a burn unit setting is highly recommended. Aggressive fluid and electrolyte replacement should be initiated early. Consults to pulmonary, gastrointestinal, and ophthalmology specialists are a must. A plastic surgeon may be very helpful with woundcare techniques to minimize additional skin trauma.
While the role of intravenous corticosteroids is still unclear, convincing studies advocate against their use because of higher mortality rates secondary to overwhelming sepsis. In smaller studies, intravenous immune globulin (IVIG) has proven very useful for SJS/TEN with halting of disease progression seen over 48 hours and a survival rate of 90%.
Cyclosporin, cyclophosphamide, and various monoclonal antibodies have met with varied success in uncontrolled clinical studies and are currently not recommended for use in children with SJS/TEN.
2. Staphylococcus-Scalded Skin Syndrome (SSSS)
SSSS is a toxin-mediated exfoliative dermatitis caused by phagogenic toxins released by Staphylococcus aureus or streptococcocal strains. These toxins create intraepidermal bullae by cleaving desmoglein 1, a cadherin that facilitates cell-to-cell cohesion of keratinocytes within the granular layer. Only about 5% of staph and strep isolates are capable of producing these protease toxins and inducing SSSS.
* While children with SSSS generally do well after antibiotic treatment, a mortality rate of 4% exists for those cases misdiagnosed or discovered late.
The presentation of SSSS. The root of original infection is typically found in the nasopharynx or in the skin as a simple impetigo. SSSS most commonly affects children younger than 5 years, often neonates, primarily because renal immaturity prevents adequate clearance of toxin. For this reason, older children with renal impairment may be at a significantly increased risk of developing SSSS.
What causes it? SSSS begins with constitutional symptoms, followed in a few days by orange-red patches that are acutely tender. Periorificial and flexural prominence is common with a progression from plaques to blisters within 48 hours. These blisters are toxin-mediated and therefore sterile. Culturing these bullae is unhelpful in clinching a diagnosis of SSSS.
The differential diagnosis of SSSS may include TEN and Kawasaki’s Disease, therefore, work-up for this condition should include epidermal frozen section. A targeted multi-culture of the nasopharynx, anus, and axilla is advised where frank cutaneous infection is not evident.
Treatment of SSSS is a straight-forward targeting of the infectious focus. This generally requires a penicillinase-resistant penicillin (such as dicloxacillin) or cephalosporin. There is some evidence to suggest that clindamycin, in addition to being anti-staphylococcal, may also decrease the release of proteolytic toxins. For this reason, I use clindamycin as first line for my children who present with SSSS.
Aggressive replenishment of fluid and electrolytes is important where a disrupted barrier may result in imbalance. Treatment of potential contacts, such as neonatal nurses and parents, with topical mupirocin is recommended to reduce colonization and recurrent infection.
3. Kawasaki’s Disease (KD)
Kawasaki’s Disease (KD) is a systemic, idiopathic vasculitis that is the most common cause of acquired cardiac disease. No infectious etiology has as of yet been confirmed for KD and the condition is particularly challenging to physicians because there is no definitive testing available for its diagnosis.
Children with major histocompatibility complexes (MHC) Bw22 and Bw22J2 are more commonly affected.
Presentation of KD is most common in boys under the age of 5 years.
The acute phase begins with LAD and fever and is followed by acral desquamation and edema. While the rash of KD is classically perineal, this exanthem is exceptionally polymorphic and may present in any form. Rash of some sort is seen in more than 90% of patients.
Non-exudative, conjunctival injection is also seen in 90% of patients, often accompanied by an anterior uveitis. Other characteristic physical findings include dry, fissured lips (80%), strawberry tongue (50%), and massive cervical lymphadenopathy (70%).
Systemic features that are variably present weeks to months after acute illness include sterile pyuria, aseptic meningitis, and testicular swelling.
Erythrocyte sedimentation rate and C-reactive protein levels, while non-specific, are both extremely elevated during the acute and subacute phases. Thrombocytosis is also prevalent and platelets may remain elevated for up to 4 weeks following defervescence.
Arthralgias and coronary aneurysm leading to sudden death are most common during the subacute phase and their emergence should be anticipated. Laboratory evaluation of KD should also include a CBC (for leukocytosis, thrombocytosis and anemia), serum chemistry (for evidence of transaminitis), and a urinalysis (for sterile pyuria). An immunoglobulin profile exhibiting elevated IgM, IgA and IgE may offer lend support to the diagnosis. A baseline EKG will reveal nonspecific abnormal findings (ST changes, prolonged PR segment), while echocardiography will exhibit any anuerysmal changes present. Clinicians must remember to repeat an echo 1 month and 3 months following acute illness, because aneurysms may develop late in a child’s disease course.
The most feared sequelae seen with KD is coronary aneurysm that may be seen in 20% to 25% of untreated children. Appropriate therapy within 10 days of onset of illness reduces this risk to about 3%. Aneurysms may be seen months after acute disease onset and prompt diagnosis by way of echocardiography is essential.
Risk factors of coronary aneurysm include male sex, pre-existing cardiac disease, prolonged illness, age <1 year, recurrence of fever after initial defervesence, and anemia with hypoalbunemia at initial visit.
Cardiology and infectious disease consults will often prove helpful in confirming a suspected case of KD.
The criteria for diagnosis of KD are: fever of unknown origin (FUO) for more than 5 days, generalized erythema and desquamation, cervical lymphadenopathy, conjunctival injection, and edema of both hands and feet.
The differential diagnosis for KD is broad because these children may have such a nonspecific presentation. Conditions that may masquerade as KD include drug eruptions, SSSS, SJS/TEN, Rocky Mountain Spotted Fever, and a host of nonspecific viral exanthems. In my practice, any child with unexplained fever, LAD, and an atypical exanthem with pedal edema will receive a Kawasaki work-up.
Treatment of KD centers upon reducing inflammation of the myocardium and coronary artery wall. Recommended therapy for KD includes IVIG as a single infusion (or once daily for 3 days) and high-dose aspirin that is tapered over 6 to 8 weeks. Smaller coronary aneurysms may regress over 2 years, while those >8 mm carry a lifetime risk of stenosis and resultant ischemic heart disease.
4. Hemangiomas of the Head and Neck
Hemangiomas of infancy (HOI) are the most common benign tumors of infancy, affecting 2% of newborn healthy infants. The vast majority of these lesions appear within the first few weeks of life and grow rapidly only to spontaneously regress before early childhood. Hemangiomas are observed more commonly in female infants and those born prematurely, occurring in a quarter of infants weighing under 1000 g. There is also a markedly higher incidence in babies born to mothers who have underwent chorionic villus sampling, a fascinating statistic that is likely related to this lesion’s poorly understood pathogenesis.
HOI classically present a few weeks after birth as bright red, occasionally telangiectatic, soft, compressible nodules or tumors. They are most commonly found on the head and neck where they pose special concerns to the treating dermatologist.
Large facial hemangiomas may be seen in association with PHACES Syndrome:
• consisting of Posterior fossa (intracranial) abnormalities
• large facial Hemangiomas
• Arterial abnormalities (i.e. aortic coarctation)
• Cardiac defects (such as atrial or ventricular septal defects)
• Eye findings (i.e. cataracts)
• Sternal defects (i.e. raphe or agenesis).
These findings are rarely found all together, therefore, the presence of a large facial hemangioma should trigger imaging of the central nervous system (CNS), consultation with an ophthalmologist, and an echocardiogram to rule out associated defects.
When a large hemangioma is found in the neck region, special consideration should be given to the possibility of laryngeal/airway involvement. While an infant may not exhibit symptoms of stridor at birth, the expected rapid proliferation of a hemangioma can result in life-threatening airway compromise very quickly.
Any infant with a mid- to large-sized hemangioma should receive an evaluation from a pediatric ENT colleague for laryngoscopic evaluation.
Smaller hemangiomas of the face are also of grave concern when found periocularly. Visual pathways are formed early in infancy and any obstruction of the visual axis can potentially lead to irreversible hemi-neglect. Evalu-ation by a pediatric ophthalmologist is usually sufficient to assess for axis obstruction, and occasionally the unaffected eye may be patched for a short time. An MR of the orbits is occasionally also required to rule out intro-orbital extension.
Treatment of hemangiomas of the head and neck that meet any of the above criteria is recommended but varies greatly depending on an infant’s age, size of the lesion, the presence of ulceration, and any immediate threat to systemic function. Even lesions of the head and neck that do not cause systemic compromise may qualify for treatment where the potential for ulceration and scar formation is great.
Smaller hemangiomas may be amenable to intralesional corticosteroid injection, although dermatologists should refrain from treating lesions abutting the orbital rim to avoid the low but appreciable risk of ophthalmic arterial embolus.
For larger HOI, most pediatric dermatologists will begin with high-dose oral prednisone in dosages ranging from 2 to 4 mg/kg/d usually for several months followed by a slow taper. Ideally, oral corticosteroids will slow, and in some cases reverse, hemangioma proliferation, however, the potential risks of corticosteroids in an infant must be weighed against their benefit.
Adjunctively, treatment with the pulsed-dye laser (585 or 595nm) may be exceptionally helpful in both lightening and slowing proliferative lesions. Where possible without grave surgical morbitity, excision may also be considered for smaller hemangiomas.
5. Melanoma (MM)
Malignant melanoma (MM) is thankfully an exceedingly rare phenomenon in the pediatric population. Nonetheless, several cases have been reported in children and it is vital that clinicians remain vigilant in assessing atypical looking nevi in patients under 18. Malignant melanoma is not only confined to children who have congenital photosensitivity disorders such as xeroderma pigmentosa and basal cell nevus syndrome.
About 2% of melanomas occur in patients under 18 and only one-quarter of these arise in pre-adolescents. Overall incidence of melanoma is increasing in the United States; currently melanoma represents 3% of all pediatric malignancies. While some mild gender predilection may exist for females, MM is generally believed to affect both sexes equally.
Clinical detection of melanoma in children is similar to that in adults, although there is some evidence to suggest that the often relied upon ABCD criteria may be even more fallible in the pediatric population. For now, this system coupled with dermoscopy is the best we have for the clinical detection.
Any lesion that is asymmetric, exhibits an irregular border, contains variegated color (greater than 3), or grows rapidly in size should be biopsied for histologic evaluation. Likewise, any symptomatic lesion (itching, pain) should be sampled.
The two most common presentations for childhood melanoma are either a rapidly growing lesion (either acquired or congenital) or a “pyogenic granuloma” type lesion that may appear red, amelanotic and friable. In my experience, patients with chromosomal abnormalities, such as Down Syndrome, should be considered a special class with an slightly increased risk of malignant lesions.
Melanoma arising out of a congenital lesion is a controversial topic and warrants special consideration. Small- and medium-sized (up to 20 cm in a child) congenital melanocytic nevi are exceptionally common and probably carry a lifetime risk of malignancy of well under 1%.
Current estimates for malignancy arising in a giant congenital melanocytic nevus (GCN) are also disparate but generally fall between 1% and 3% with a few notable estimates that lie much higher. When malignancy does arise from a GCN, it typically does so within the first decade of life. While some authors suggest prophylactic removal of any GCN early in life, even extensive excisions cannot protect against melanoma development deep within facial planes.
Treatment consisting of excision of atypical or “dysplastic” nevi, whether congenital or acquired, is standard of care for the prevention of malignant deterioration. The vast majority of these procedures result in definitive prevention with a near zero risk of recurrence.
Pediatric melanoma usually presents deeper and with a poorer prognosis than its adult counterpart, most likely because of a delay in diagnosis.
When deeper (i.e. >1 mm) melanomas are discovered, sentinel lymph node biopsy is a minimally invasive procedure that is helpful in identifying metastasis-in-transit.
Where involvement of a lymphatic basin is identified, removing nodes and enrolling the patient in one of several experimental protocols such as interferon is customary.
Children with a previous diagnosis of severely dysplastic nevi or melanoma are at a far greater risk of a second malignant lesion and should be followed closely for the development of additional lesions.
6. Langerhans’ Cell Histiocytosis (LCH)
Langerhans’ cell histiocytosis (LCH) is a group of disorders characterized by the idiopathic proliferation of specialized lymphocytes, called Langherhans cells. These dendritic cells provide immune system surveillance within the epidermis. An uncontrolled dissemination of this cell subset may result in fulminant organ failure (previously termed Letterer-Siwe) or a solitary indolent lesion (previously termed eosinophilic granuloma). Whether this proliferation is neoplastic or reactive is unknown.
LCH is rare, affecting 1 to 5 people per million per year. The local form of LCH, while indolent, is not life-threatening.
The disseminated form of LCH is rapidly lethal in 50% of infants under the age of 2 years.
The disease presents with symptoms that may mimic systemic malignancy with fever, anemia and hepato-splenomegaly.
Cutaneous lesions are often a promontory sign of LCH and consist of eroded, crusted papules in a perioraficial, predominantly perineum and perioral, location.
LCH may be painless or may result in significant pain if bony involvement is present. LCH with bone involvement can have morbid mass effects, such as fractures, propotosis and pituitary dysfunction, when bony lesions affect adjacent parenchyma. After bone, lymph node, spleen, and liver involvement are most common.
The differential diagnosis of LCH includes seborrheic dermatitis and erythema toxicum neonatorum. LCH may be best differentiated from these more common entities by its failure to respond to traditional therapy.
The work-up of LCH requires a CBC and, in the case of pancytopenia, a bone marrow aspirate to evaluate for skeletal involvement. Liver function enzymes should be assessed and, in the case of transaminitis, a liver biopsy should be performed to assess the extent of liver involvement. As the sella tursica is commonly involved, a urine osmolarity may be helpful to screen for diabetes insipidus. A chest X-ray and skeletal survey is recommended where systemic LCH is suspected. In cases of severe dissemination, a MR image of the CNS should be considered to evaluate for cerebral involvement. A skin biopsy is exceptionally helpful in arriving at a diagnosis of LCH.
The treatment of LCH is determined in large part by extent of disease. Mild forms do not require treatment at all, while multicentric LCH with organ involvement may be treated with systemic steroids or in some cases targeted radiation. Mild skin only involvement may be treated with topical steroids, while moderate to severe skin only disease may benefit from PUVA or topical nitrogen mustard (20%).
Recognizing the “Big 6”
Thankfully, the vast majority of pediatric dermatoses are non-threatening, however, clinicians should be aware of those conditions that when caught early may be treated successfully without permanent morbidity. The “Big 6” conditions discussed above are conditions that can be recognized and treated early in their course to avoid a poor prognosis.
Life-threatening pediatric dermatoses, while rare, can be particularly devastating for patients. Clinicians are often lulled by the benignity of most childhood disorders. However, without a vigilant index of suspicion, many potentially morbid conditions may be discovered too late for appropriate management. This article will review the presentation, treatment, and prognosis of several of the more common and more destructive dermatoses seen in children and adolescents. They are toxic epidermal necrolysis (TEN), staphylococcal scalded skin syndrome (SSSS), Kawasaki’s Disease (KD), hemangiomas of the head and neck, pediatric melanoma, and Langerhans’ cell histiocytosis (LCH). These conditions range in origin from the inflammatory to the infectious to the neoplastic and comprise the “Big 6” that dermatologists should strive to recognize early in their presentation.
1. SJS/TEN
Perhaps the most life-threatening and rapidly progressive emergency in pediatric dermatology is the spectrum of disease encompassing Stevens Johnson syndrome and toxic epidermal necrolysis. These two entities are characterized by widespread erythematous, edematous plaques with prominent mucosal involvement. Nearly all cases of TEN and SJS are medication-induced and overall mortality may approach 40%. This spectrum is one of the few dermatologic conditions where full-thickness epidermal necrosis is observed.
What causes it? The pathogenesis of SJS/TEN is poorly understood, however, there appears to be some genetic component, because first-degree relatives may be similarly affected when exposed to an offending medication such as sulfa derivative.
The accumulation of toxic metabolites from these agents may be responsible for cell apoptosis and the onset of disease. Some studies suggest that the inappropriate release of perforins may be responsible for unmediated keratinocyte death. There is more recent, convincing data to suggest that a cell-surface “death receptor” (Fas) and an increase in its triggering ligand (FasL) may be responsible for the onset of disease. IVIG therapy is specifically designed to block this interaction and will be discussed later in more detail as a therapeutic option.
The incidence of SJS/TEN is rare, ranging from 0.5 to 1.2 per million per population year. The direct cause of death among those patients with poor outcomes is sepsis (owing to a compromised epidermal barrier) and respiratory distress. Prognostic factors include high body surface area (BSA) involvement, hypoalbunemia (<2 g/dl), greater than 5 days of neutropenia, and persistent azotemia.
Children who do well normally re-epithelialize within 3 weeks.
* The most serious long-term sequelae for survivors of SJS/TEN involve the eye, with conjunctival erosions and cicatrisation accounting for significant morbidity in up to 40% of children. No gender predilection exists for pediatric SJS/TEN, and the condition may occur at any age.
The presentation of SJS typically begins with constitutional symptoms a few days prior to any cutaneous lesion. Itching of the conjunctiva or photophobia may be an early symptom.
Early skin lesions are poorly defined edematous plaques with dusky or purpuric centers. A careful medication history will usually reveal the offending agent. Sulfonamide antibiotics are the most commonly implicated, but case reports exist for an innumerable number of pharmacologic incitors.
Flaccid bullae, where present, arise once epidermal necrosis sets in. Acral involvement is also common. Internal involvement most commonly includes the gastrointestinal and respiratory systems and can be devastating.
The differential diagnosis for SJS/TEN is somewhat limited owing in large part to its unmistakable fulminant presentation. Graft versus host disease and staphylococcal or streptococcal scalded skin syndrome may mimic SJS/TEN focally, but the latter do not exhibit full thickness sloughing and prominent mucosal involvement.
The work-up for suspected SJS/TEN should include a complete blood cell count, SMA20, and coagulation profile to rule out emerging disseminated intravascular coagulation (DIC). Cultures of denuded skin and blood are also important to assess for any superinfection and possible sepsis. A baseline A/P chest film should be obtained as tracheo-bronchial involvement is a dreaded complication. A snap frozen section of denuded skin taken from the bedside can clinch a diagnosis of SJS/TEN within minutes.
Treatment of SJS/TEN is decidedly controversial. One thing is certain: stop the offending medication. A multidisciplinary approach within a burn unit setting is highly recommended. Aggressive fluid and electrolyte replacement should be initiated early. Consults to pulmonary, gastrointestinal, and ophthalmology specialists are a must. A plastic surgeon may be very helpful with woundcare techniques to minimize additional skin trauma.
While the role of intravenous corticosteroids is still unclear, convincing studies advocate against their use because of higher mortality rates secondary to overwhelming sepsis. In smaller studies, intravenous immune globulin (IVIG) has proven very useful for SJS/TEN with halting of disease progression seen over 48 hours and a survival rate of 90%.
Cyclosporin, cyclophosphamide, and various monoclonal antibodies have met with varied success in uncontrolled clinical studies and are currently not recommended for use in children with SJS/TEN.
2. Staphylococcus-Scalded Skin Syndrome (SSSS)
SSSS is a toxin-mediated exfoliative dermatitis caused by phagogenic toxins released by Staphylococcus aureus or streptococcocal strains. These toxins create intraepidermal bullae by cleaving desmoglein 1, a cadherin that facilitates cell-to-cell cohesion of keratinocytes within the granular layer. Only about 5% of staph and strep isolates are capable of producing these protease toxins and inducing SSSS.
* While children with SSSS generally do well after antibiotic treatment, a mortality rate of 4% exists for those cases misdiagnosed or discovered late.
The presentation of SSSS. The root of original infection is typically found in the nasopharynx or in the skin as a simple impetigo. SSSS most commonly affects children younger than 5 years, often neonates, primarily because renal immaturity prevents adequate clearance of toxin. For this reason, older children with renal impairment may be at a significantly increased risk of developing SSSS.
What causes it? SSSS begins with constitutional symptoms, followed in a few days by orange-red patches that are acutely tender. Periorificial and flexural prominence is common with a progression from plaques to blisters within 48 hours. These blisters are toxin-mediated and therefore sterile. Culturing these bullae is unhelpful in clinching a diagnosis of SSSS.
The differential diagnosis of SSSS may include TEN and Kawasaki’s Disease, therefore, work-up for this condition should include epidermal frozen section. A targeted multi-culture of the nasopharynx, anus, and axilla is advised where frank cutaneous infection is not evident.
Treatment of SSSS is a straight-forward targeting of the infectious focus. This generally requires a penicillinase-resistant penicillin (such as dicloxacillin) or cephalosporin. There is some evidence to suggest that clindamycin, in addition to being anti-staphylococcal, may also decrease the release of proteolytic toxins. For this reason, I use clindamycin as first line for my children who present with SSSS.
Aggressive replenishment of fluid and electrolytes is important where a disrupted barrier may result in imbalance. Treatment of potential contacts, such as neonatal nurses and parents, with topical mupirocin is recommended to reduce colonization and recurrent infection.
3. Kawasaki’s Disease (KD)
Kawasaki’s Disease (KD) is a systemic, idiopathic vasculitis that is the most common cause of acquired cardiac disease. No infectious etiology has as of yet been confirmed for KD and the condition is particularly challenging to physicians because there is no definitive testing available for its diagnosis.
Children with major histocompatibility complexes (MHC) Bw22 and Bw22J2 are more commonly affected.
Presentation of KD is most common in boys under the age of 5 years.
The acute phase begins with LAD and fever and is followed by acral desquamation and edema. While the rash of KD is classically perineal, this exanthem is exceptionally polymorphic and may present in any form. Rash of some sort is seen in more than 90% of patients.
Non-exudative, conjunctival injection is also seen in 90% of patients, often accompanied by an anterior uveitis. Other characteristic physical findings include dry, fissured lips (80%), strawberry tongue (50%), and massive cervical lymphadenopathy (70%).
Systemic features that are variably present weeks to months after acute illness include sterile pyuria, aseptic meningitis, and testicular swelling.
Erythrocyte sedimentation rate and C-reactive protein levels, while non-specific, are both extremely elevated during the acute and subacute phases. Thrombocytosis is also prevalent and platelets may remain elevated for up to 4 weeks following defervescence.
Arthralgias and coronary aneurysm leading to sudden death are most common during the subacute phase and their emergence should be anticipated. Laboratory evaluation of KD should also include a CBC (for leukocytosis, thrombocytosis and anemia), serum chemistry (for evidence of transaminitis), and a urinalysis (for sterile pyuria). An immunoglobulin profile exhibiting elevated IgM, IgA and IgE may offer lend support to the diagnosis. A baseline EKG will reveal nonspecific abnormal findings (ST changes, prolonged PR segment), while echocardiography will exhibit any anuerysmal changes present. Clinicians must remember to repeat an echo 1 month and 3 months following acute illness, because aneurysms may develop late in a child’s disease course.
The most feared sequelae seen with KD is coronary aneurysm that may be seen in 20% to 25% of untreated children. Appropriate therapy within 10 days of onset of illness reduces this risk to about 3%. Aneurysms may be seen months after acute disease onset and prompt diagnosis by way of echocardiography is essential.
Risk factors of coronary aneurysm include male sex, pre-existing cardiac disease, prolonged illness, age <1 year, recurrence of fever after initial defervesence, and anemia with hypoalbunemia at initial visit.
Cardiology and infectious disease consults will often prove helpful in confirming a suspected case of KD.
The criteria for diagnosis of KD are: fever of unknown origin (FUO) for more than 5 days, generalized erythema and desquamation, cervical lymphadenopathy, conjunctival injection, and edema of both hands and feet.
The differential diagnosis for KD is broad because these children may have such a nonspecific presentation. Conditions that may masquerade as KD include drug eruptions, SSSS, SJS/TEN, Rocky Mountain Spotted Fever, and a host of nonspecific viral exanthems. In my practice, any child with unexplained fever, LAD, and an atypical exanthem with pedal edema will receive a Kawasaki work-up.
Treatment of KD centers upon reducing inflammation of the myocardium and coronary artery wall. Recommended therapy for KD includes IVIG as a single infusion (or once daily for 3 days) and high-dose aspirin that is tapered over 6 to 8 weeks. Smaller coronary aneurysms may regress over 2 years, while those >8 mm carry a lifetime risk of stenosis and resultant ischemic heart disease.
4. Hemangiomas of the Head and Neck
Hemangiomas of infancy (HOI) are the most common benign tumors of infancy, affecting 2% of newborn healthy infants. The vast majority of these lesions appear within the first few weeks of life and grow rapidly only to spontaneously regress before early childhood. Hemangiomas are observed more commonly in female infants and those born prematurely, occurring in a quarter of infants weighing under 1000 g. There is also a markedly higher incidence in babies born to mothers who have underwent chorionic villus sampling, a fascinating statistic that is likely related to this lesion’s poorly understood pathogenesis.
HOI classically present a few weeks after birth as bright red, occasionally telangiectatic, soft, compressible nodules or tumors. They are most commonly found on the head and neck where they pose special concerns to the treating dermatologist.
Large facial hemangiomas may be seen in association with PHACES Syndrome:
• consisting of Posterior fossa (intracranial) abnormalities
• large facial Hemangiomas
• Arterial abnormalities (i.e. aortic coarctation)
• Cardiac defects (such as atrial or ventricular septal defects)
• Eye findings (i.e. cataracts)
• Sternal defects (i.e. raphe or agenesis).
These findings are rarely found all together, therefore, the presence of a large facial hemangioma should trigger imaging of the central nervous system (CNS), consultation with an ophthalmologist, and an echocardiogram to rule out associated defects.
When a large hemangioma is found in the neck region, special consideration should be given to the possibility of laryngeal/airway involvement. While an infant may not exhibit symptoms of stridor at birth, the expected rapid proliferation of a hemangioma can result in life-threatening airway compromise very quickly.
Any infant with a mid- to large-sized hemangioma should receive an evaluation from a pediatric ENT colleague for laryngoscopic evaluation.
Smaller hemangiomas of the face are also of grave concern when found periocularly. Visual pathways are formed early in infancy and any obstruction of the visual axis can potentially lead to irreversible hemi-neglect. Evalu-ation by a pediatric ophthalmologist is usually sufficient to assess for axis obstruction, and occasionally the unaffected eye may be patched for a short time. An MR of the orbits is occasionally also required to rule out intro-orbital extension.
Treatment of hemangiomas of the head and neck that meet any of the above criteria is recommended but varies greatly depending on an infant’s age, size of the lesion, the presence of ulceration, and any immediate threat to systemic function. Even lesions of the head and neck that do not cause systemic compromise may qualify for treatment where the potential for ulceration and scar formation is great.
Smaller hemangiomas may be amenable to intralesional corticosteroid injection, although dermatologists should refrain from treating lesions abutting the orbital rim to avoid the low but appreciable risk of ophthalmic arterial embolus.
For larger HOI, most pediatric dermatologists will begin with high-dose oral prednisone in dosages ranging from 2 to 4 mg/kg/d usually for several months followed by a slow taper. Ideally, oral corticosteroids will slow, and in some cases reverse, hemangioma proliferation, however, the potential risks of corticosteroids in an infant must be weighed against their benefit.
Adjunctively, treatment with the pulsed-dye laser (585 or 595nm) may be exceptionally helpful in both lightening and slowing proliferative lesions. Where possible without grave surgical morbitity, excision may also be considered for smaller hemangiomas.
5. Melanoma (MM)
Malignant melanoma (MM) is thankfully an exceedingly rare phenomenon in the pediatric population. Nonetheless, several cases have been reported in children and it is vital that clinicians remain vigilant in assessing atypical looking nevi in patients under 18. Malignant melanoma is not only confined to children who have congenital photosensitivity disorders such as xeroderma pigmentosa and basal cell nevus syndrome.
About 2% of melanomas occur in patients under 18 and only one-quarter of these arise in pre-adolescents. Overall incidence of melanoma is increasing in the United States; currently melanoma represents 3% of all pediatric malignancies. While some mild gender predilection may exist for females, MM is generally believed to affect both sexes equally.
Clinical detection of melanoma in children is similar to that in adults, although there is some evidence to suggest that the often relied upon ABCD criteria may be even more fallible in the pediatric population. For now, this system coupled with dermoscopy is the best we have for the clinical detection.
Any lesion that is asymmetric, exhibits an irregular border, contains variegated color (greater than 3), or grows rapidly in size should be biopsied for histologic evaluation. Likewise, any symptomatic lesion (itching, pain) should be sampled.
The two most common presentations for childhood melanoma are either a rapidly growing lesion (either acquired or congenital) or a “pyogenic granuloma” type lesion that may appear red, amelanotic and friable. In my experience, patients with chromosomal abnormalities, such as Down Syndrome, should be considered a special class with an slightly increased risk of malignant lesions.
Melanoma arising out of a congenital lesion is a controversial topic and warrants special consideration. Small- and medium-sized (up to 20 cm in a child) congenital melanocytic nevi are exceptionally common and probably carry a lifetime risk of malignancy of well under 1%.
Current estimates for malignancy arising in a giant congenital melanocytic nevus (GCN) are also disparate but generally fall between 1% and 3% with a few notable estimates that lie much higher. When malignancy does arise from a GCN, it typically does so within the first decade of life. While some authors suggest prophylactic removal of any GCN early in life, even extensive excisions cannot protect against melanoma development deep within facial planes.
Treatment consisting of excision of atypical or “dysplastic” nevi, whether congenital or acquired, is standard of care for the prevention of malignant deterioration. The vast majority of these procedures result in definitive prevention with a near zero risk of recurrence.
Pediatric melanoma usually presents deeper and with a poorer prognosis than its adult counterpart, most likely because of a delay in diagnosis.
When deeper (i.e. >1 mm) melanomas are discovered, sentinel lymph node biopsy is a minimally invasive procedure that is helpful in identifying metastasis-in-transit.
Where involvement of a lymphatic basin is identified, removing nodes and enrolling the patient in one of several experimental protocols such as interferon is customary.
Children with a previous diagnosis of severely dysplastic nevi or melanoma are at a far greater risk of a second malignant lesion and should be followed closely for the development of additional lesions.
6. Langerhans’ Cell Histiocytosis (LCH)
Langerhans’ cell histiocytosis (LCH) is a group of disorders characterized by the idiopathic proliferation of specialized lymphocytes, called Langherhans cells. These dendritic cells provide immune system surveillance within the epidermis. An uncontrolled dissemination of this cell subset may result in fulminant organ failure (previously termed Letterer-Siwe) or a solitary indolent lesion (previously termed eosinophilic granuloma). Whether this proliferation is neoplastic or reactive is unknown.
LCH is rare, affecting 1 to 5 people per million per year. The local form of LCH, while indolent, is not life-threatening.
The disseminated form of LCH is rapidly lethal in 50% of infants under the age of 2 years.
The disease presents with symptoms that may mimic systemic malignancy with fever, anemia and hepato-splenomegaly.
Cutaneous lesions are often a promontory sign of LCH and consist of eroded, crusted papules in a perioraficial, predominantly perineum and perioral, location.
LCH may be painless or may result in significant pain if bony involvement is present. LCH with bone involvement can have morbid mass effects, such as fractures, propotosis and pituitary dysfunction, when bony lesions affect adjacent parenchyma. After bone, lymph node, spleen, and liver involvement are most common.
The differential diagnosis of LCH includes seborrheic dermatitis and erythema toxicum neonatorum. LCH may be best differentiated from these more common entities by its failure to respond to traditional therapy.
The work-up of LCH requires a CBC and, in the case of pancytopenia, a bone marrow aspirate to evaluate for skeletal involvement. Liver function enzymes should be assessed and, in the case of transaminitis, a liver biopsy should be performed to assess the extent of liver involvement. As the sella tursica is commonly involved, a urine osmolarity may be helpful to screen for diabetes insipidus. A chest X-ray and skeletal survey is recommended where systemic LCH is suspected. In cases of severe dissemination, a MR image of the CNS should be considered to evaluate for cerebral involvement. A skin biopsy is exceptionally helpful in arriving at a diagnosis of LCH.
The treatment of LCH is determined in large part by extent of disease. Mild forms do not require treatment at all, while multicentric LCH with organ involvement may be treated with systemic steroids or in some cases targeted radiation. Mild skin only involvement may be treated with topical steroids, while moderate to severe skin only disease may benefit from PUVA or topical nitrogen mustard (20%).
Recognizing the “Big 6”
Thankfully, the vast majority of pediatric dermatoses are non-threatening, however, clinicians should be aware of those conditions that when caught early may be treated successfully without permanent morbidity. The “Big 6” conditions discussed above are conditions that can be recognized and treated early in their course to avoid a poor prognosis.
