Overview
Definition:
Severe atopic dermatitis (AD) in adolescents is a chronic, relapsing inflammatory skin condition characterized by intense pruritus and eczematous lesions, significantly impacting quality of life
Biologics are targeted therapies that modulate specific immune pathways involved in AD pathogenesis, offering a new paradigm for managing severe disease unresponsive to conventional treatments.
Epidemiology:
Atopic dermatitis affects 10-20% of children worldwide, with approximately 15-30% of these cases being severe
In adolescents, severe AD persists in a significant proportion, often leading to considerable physical and psychological distress
The prevalence of severe AD requiring systemic therapy, including biologics, is estimated to be around 1-3% in this age group.
Clinical Significance:
Severe atopic dermatitis in teens can lead to chronic sleep deprivation, impaired social functioning, anxiety, depression, and increased risk of skin infections
Biologics represent a critical advancement, offering effective disease control, improved quality of life, and reduced need for broad immunosuppressants in a population with developing immune systems
Understanding their role is vital for pediatricians and residents preparing for DNB and NEET SS exams.
Clinical Presentation
Symptoms:
Intense, intractable pruritus, often worse at night
Erythematous, ill-defined papules and plaques
Excoriations and lichenification from chronic scratching
Dry, scaly skin
Oozing and crusting in acute flares
Location of lesions typically includes flexural areas (antecubital and popliteal fossae), face, neck, and hands, though can be widespread
Associated symptoms may include sleep disturbance, anxiety, and social withdrawal.
Signs:
Erythema, edema, and papules in affected areas
Lichenification (thickening of the skin with accentuated skin markings) due to chronic rubbing and scratching
Crusting and oozing, indicative of secondary bacterial infection
Xerosis (dryness) of the skin
Distribution pattern consistent with AD, though can be generalized in severe cases
Posterior auricular creases and Dennie-Morgan lines may be present.
Diagnostic Criteria:
Diagnosis of AD is primarily clinical, often based on Hanifin and Rajka criteria
Key elements include pruritus, characteristic morphology and distribution of lesions, chronicity (recurrent flares), and personal or family history of atopy (asthma, allergic rhinitis)
For severe disease requiring biologics, objective measures like SCORAD (Scoring of Atopic Dermatitis) or EASI (Eczema Area and Severity Index) scores are used to quantify disease severity, with typical thresholds for initiating biologics being high SCORAD (>40) or moderate-to-severe EASI (>16).
Diagnostic Approach
History Taking:
Detailed history of pruritus intensity and triggers
Pattern and duration of flares
Previous treatments and response
History of asthma, allergic rhinitis, food allergies
Family history of atopy
Impact on sleep, school, and social life
Red flags: signs of widespread infection, failure to thrive, significant psychological distress.
Physical Examination:
Thorough assessment of skin for erythema, edema, papules, plaques, excoriations, lichenification, and xerosis
Assess distribution and severity of lesions
Examine for signs of secondary infection (impetiginization, cellulitis)
Assess for characteristic facial findings (e.g., periorbital darkening)
Evaluate nail changes (e.g., brittle nails, koilonychia).
Investigations:
Typically, no specific laboratory investigations are required for diagnosis of AD itself
However, in severe or recalcitrant cases, investigations may include: Complete Blood Count (CBC) with eosinophil count (often elevated)
Serum IgE levels (often elevated, but not diagnostic)
Skin swabs for bacterial culture and sensitivity if secondary infection is suspected
Allergy testing (skin prick tests or specific IgE blood tests) for identification of common triggers, though not routinely used to guide biologic therapy selection
Patch testing for contact dermatitis in select cases.
Differential Diagnosis:
Other forms of eczema (e.g., irritant contact dermatitis, allergic contact dermatitis)
Psoriasis
Fungal infections (tinea)
Pityriasis rosea
Cutaneous T-cell lymphoma (mycosis fungoides)
Scabies
Seborrheic dermatitis
Lymphoma
Differentiating features include lesion morphology, distribution, presence of specific signs like Auspitz sign in psoriasis, or characteristic distribution in fungal infections.
Management
Initial Management:
Aggressive and comprehensive
Gentle skin care: mild cleansers, frequent emollients (barrier creams)
Avoidance of triggers (irritants, allergens)..
Medical Management:
Topical corticosteroids: potent to super-potent for flares, to be used judiciously for short durations
Topical calcineurin inhibitors (tacrolimus, pimecrolimus) for sensitive areas or maintenance therapy
Systemic therapies: phototherapy (NB-UVB)
Oral corticosteroids (short courses for severe flares)
Immunomodulatory agents (cyclosporine, methotrexate, azathioprine) for recalcitrant cases
Biologics: Dupilumab (anti-IL-4/IL-13 monoclonal antibody) and Tralokinumab (anti-IL-13 monoclonal antibody) are approved for moderate-to-severe AD in adolescents
Dosing for Dupilumab: 600 mg subcutaneously initially, followed by 300 mg every two weeks
Dosing for Tralokinumab: 600 mg subcutaneously initially, followed by 300 mg every two weeks
Dosing regimens may vary based on weight and specific product labeling.
Surgical Management:
Generally not indicated for atopic dermatitis itself
Surgical interventions may be considered for complications such as severe chronic lichenification requiring debridement or for management of secondary infections that require drainage.
Supportive Care:
Patient and family education on disease management, trigger avoidance, and proper skincare
Psychological support for patients and families to address the impact on quality of life
Management of secondary infections with appropriate antibiotics
Nutritional assessment if food allergies are suspected
Regular follow-up to monitor treatment efficacy and safety.
Biologics In Detail
Mechanism Of Action:
Biologics target specific cytokines or immune cells central to AD pathogenesis
Dupilumab targets the shared alpha subunit of the IL-4 and IL-13 receptor, inhibiting signaling of both key cytokines involved in Th2 inflammation and skin barrier dysfunction
Tralokinumab specifically binds to and neutralizes IL-13, another critical driver of Th2 inflammation in AD.
Indications And Selection:
Indicated for moderate-to-severe atopic dermatitis in adolescents aged 12 years and older who are inadequately controlled with topical therapies or for whom such therapies are inadvisable
Selection may depend on local availability, physician preference, and patient-specific factors or comorbidities.
Efficacy And Outcomes:
Clinical trials demonstrate significant improvement in EASI scores, SCORING AD, pruritus, and quality of life in adolescents treated with dupilumab and tralokinumab
Sustained disease control is often observed with continued therapy
These agents can reduce the need for oral corticosteroids and improve sleep and daily functioning.
Adverse Effects And Monitoring:
Common adverse effects include injection site reactions (erythema, pain, swelling), conjunctivitis (more frequent with dupilumab), and herpes simplex infections
Less common but serious effects can include hypersensitivity reactions
Regular monitoring for efficacy, safety, and potential adverse events, including eye examinations and assessment for infections, is crucial.
Complications
Early Complications:
Secondary bacterial infections (e.g., Staphylococcus aureus impetiginization, cellulitis) due to compromised skin barrier and immunosuppression
Viral infections (e.g., eczema herpeticum)..
Late Complications:
Chronic skin changes (severe lichenification, scarring)
Growth retardation in severe, untreated AD
Ocular complications (cataracts, keratoconus) can be exacerbated or associated with AD
Psychological impact (depression, anxiety, social isolation)..
Prevention Strategies:
Strict adherence to emollients and gentle skincare to maintain skin barrier function
Prompt treatment of secondary infections
Patient and family education on recognizing and managing flares and infections
Careful monitoring for ocular and psychological comorbidities
Judicious use of immunosuppressants and biologics with appropriate safety monitoring.
Prognosis
Factors Affecting Prognosis:
Severity and duration of disease
Age of onset
Presence of comorbidities (asthma, allergic rhinitis)
Adherence to treatment
Response to therapy
Genetic factors.
Outcomes:
With effective management, including biologics for severe cases, the prognosis for adolescents with atopic dermatitis is generally good, with significant improvement in disease control and quality of life
Many patients experience periods of remission
However, AD can be a lifelong condition for some.
Follow Up:
Regular follow-up appointments are essential for ongoing disease assessment, adjustment of treatment strategies, monitoring for adverse effects of medications (especially biologics), and managing comorbidities
The frequency of follow-up is determined by disease severity and treatment response, typically ranging from every 3-6 months.
Key Points
Exam Focus:
Understand the pathophysiology of AD with emphasis on IL-4, IL-13, and Th2 immunity
Know the specific indications and contraindications for biologics like dupilumab and tralokinumab in adolescents
Recall typical dosing regimens for these biologics
Recognize common side effects and monitoring requirements.
Clinical Pearls:
Always assess the impact of pruritus on sleep and quality of life
this is a key determinant of severity
Emphasize barrier repair with emollients as the cornerstone of all AD management, even when using biologics
Consider secondary infections in any acute flare or worsening of AD
Develop a clear plan for taper and discontinuation of topical steroids when initiating biologics.
Common Mistakes:
Underestimating the severity of pruritus and its impact
Inadequate use of emollients
Over-reliance on topical steroids for prolonged periods without considering systemic or biologic options for severe disease
Failing to screen for or manage secondary infections
Not monitoring for specific side effects of biologics, such as conjunctivitis.