Introduction

Dupilumab (Dupixent®) is a monoclonal antibody therapy designed to treat inflammatory conditions, primarily atopic dermatitis. It is the first biologic treatment approved for moderate to severe atopic dermatitis and has since been expanded to other allergic and inflammatory diseases. By blocking specific immune signaling pathways, dupilumab offers an effective alternative for patients who do not respond adequately to conventional therapies.

Mechanism of Action

Dupilumab is a human IgG4 monoclonal antibody that specifically binds to the IL-4Rα subunit, a key component of the receptor shared by interleukin-4 (IL-4) and interleukin-13 (IL-13). These two cytokines play a crucial role in Th2-mediated inflammation, which is a major driver of conditions like atopic dermatitis and asthma. By inhibiting IL-4 and IL-13 signaling, dupilumab reduces inflammation, improves skin barrier function, and alleviates symptoms.

Indications

Dupilumab is FDA-approved for the treatment of:

• Atopic dermatitis (eczema) in patients ≥6 months old with moderate-to-severe disease that is inadequately controlled with topical treatments.
• Prurigo nodularis in adults.
• Asthma in patients ≥6 years old with moderate-to-severe disease.
• Eosinophilic esophagitis in patients ≥12 years old.
• Chronic rhinosinusitis with nasal polyps in adults.

Additionally, off-label uses of dupilumab are being explored for spontaneous chronic urticaria, nummular eczema, allergic contact dermatitis, chronic hand eczema, bullous pemphigoid, and Netherton syndrome.

Dosage and Administration

Dupilumab is administered via subcutaneous injection, with dosing dependent on age and weight:

• Adults and children (≥60 kg): 600 mg loading dose, then 300 mg every 2 weeks.
• Children (30–59 kg): 400 mg loading dose, then 200 mg every 2 weeks.
• Children (15–29 kg, ≥6 years old): 600 mg loading dose, then 300 mg every 4 weeks.
• Children (5–14 kg, ≤5 years old): 200 mg every 4 weeks.

Contraindications and Precautions

Dupilumab is contraindicated in patients with a known hypersensitivity to the drug or its components. Additionally, live vaccines should be avoided, and patients should be up to date on their vaccinations before starting therapy.

Patients with serious active helminth infections (parasitic worms) should be treated before starting dupilumab.

Adverse Effects

While generally well-tolerated, dupilumab can cause certain side effects, the most common being:

• Injection site reactions
• Ocular diseases (conjunctivitis, dry eyes, blepharitis, keratitis)
• Herpes infections
• Atopic dermatitis exacerbation
• Nasopharyngitis (common cold symptoms)
• Headache and upper respiratory infections

Ocular side effects occur in approximately 10% of patients and usually develop within the first few weeks to months of treatment. Artificial tears, antihistamine eye drops (e.g., ketotifen), corticosteroids, cyclosporine, and tacrolimus ointment may be used for management.

Some patients may also experience facial or neck erythema, or dermatitis that is possibly linked to rosacea, allergic contact dermatitis, or Malassezia related dermatitis. 

Rare but reported conditions associated with dupilumab include psoriasiform eruptions, lichen planus-like reactions, and eosinophilic granulomatosis with polyangiitis.

Clinical Outcomes and Efficacy

Clinical trials have demonstrated that 40–50% of adolescents and adults receiving dupilumab alone, and 60–70% of children or adults receiving it in combination with topical corticosteroids, achieve a 75% improvement in their Eczema Area and Severity Index (EASI-75).

Conclusion

Dupilumab has revolutionized the management of atopic dermatitis and other Th2-driven inflammatory conditions, offering a safe and effective option for patients with moderate-to-severe disease. While its side effects, particularly ocular symptoms, should be monitored, its benefits in reducing inflammation and improving quality of life make it a cornerstone therapy in dermatology and beyond.

Written by: 

Naif Alshehri, Medical Intern 

Resources: 

Saudi MOH Atopic Dermatitis Guidelines

Dermnet

Bolognia Dermatology Textbook 5th Edition

Muñoz-Bellido FJ, Moreno E, Dávila I. Dupilumab: A Review of Present Indications and Off-Label Uses. J Investig Allergol Clin Immunol. 2022;32(2):97-115. doi:10.18176/jiaci.0682

Second Picture Resource:

Bolognia Dermatology Textbook 5th Edition

Introduction

Pyogenic granuloma, also known as lobular capillary hemangioma, granuloma gravidarum, or pregnancy tumor, is a benign vascular lesion characterized by the rapid proliferation of capillary blood vessels in the skin or mucosa. Despite its name, it is neither pyogenic nor granulomatous. Modern research shows it arises due to reactive neovascularization without any infectious involvement.

Epidemiology

Pyogenic granulomas (PGs) can develop at any age but are most common in children, teenagers, and young adults. A slight male predominance is observed overall, except for oral lesions, which are more frequent in females due to hormonal influences like pregnancy or oral contraceptive use. Rare presentations include neonates with multifocal PGs or adults with eruptive disseminated forms.

Etiology and Pathogenesis

PGs are often linked to pre-existing trauma or irritation, hormonal changes, or specific medications. Minor trauma accounts for 7% of cases, while oral lesions are commonly associated with chronic irritation and poor dental hygiene. Hormonal changes during pregnancy or contraceptive use are significant factors, with 5% of pregnant women developing gingival PGs.
Medications like retinoids, protease inhibitors, and cancer-targeted therapies can also trigger PGs. Additionally, molecular studies have identified mutations in the BRAF and NRAS genes, which activate the MAPK signaling pathway, suggesting a neoplastic component in some cases.

Clinical Features

PGs typically present as painless, red nodules or polyps that grow rapidly over weeks. The lesions are highly friable, frequently ulcerating or bleeding after minor trauma. They stabilize at sizes usually under 1 cm but may persist indefinitely if untreated. Common sites include the gingiva, lips, fingers, face, and tongue.

Oral mucosal PGs often develop as pedunculated or sessile nodules on the gums or lips. These lesions may ulcerate, develop a yellow fibrinous surface, and cause minor discomfort. Rarely, satellite lesions may arise near a primary PG after trauma or irritation.

Dermoscopy and Histology

Dermoscopy
Dermoscopy reveals a distinct keratinized border forming a white collarette around the lesion. Vascular structures are prominent, with red homogeneous areas and white linear “rail lines” being hallmark features.

Histological Findings
Histologically, PGs are characterized by a lobular arrangement of capillaries in the dermis surrounded by inflammatory cells and fibromyxoid stroma. The epidermis is often thinned or ulcerated, and a peripheral collarette formed by elongated rete ridges is typically present. Signs of hemorrhage and inflammatory infiltrates, including lymphocytes and plasma cells, are common. Oral PGs may show an additional granulation tissue-like vascular proliferation pattern.

Differential Diagnosis

The differential diagnosis for PG depends on its location and presentation:

Cutaneous Differential Diagnosis

• Amelanotic melanoma: Most critical to exclude due to overlapping features.
• Bacillary angiomatosis: Especially in immunosuppressed patients.
• Kaposi sarcoma: Seen in HIV-positive individuals.
• Cherry angioma: Benign capillary proliferation.
• Irritated melanocytic nevus or wart: May mimic PG due to irritation.

Oral Differential Diagnosis

• Peripheral giant cell granuloma
• Peripheral ossifying fibroma

Histological Differential Diagnosis

• Cherry angioma
• Bacillary angiomatosis

Treatment

Treatment focuses on lesion removal and addressing contributing factors to prevent recurrence. Options include:

• • General Measures: Improving oral hygiene, removing trauma sources, and discontinuing triggering medications.
  • Topical Treatments: Timolol gel, imiquimod cream, cryotherapy, or table salt therapy (applied under occlusion).

• Procedural Treatments:

• • Shave excision with electrosurgery: The most common approach.
  • Curettage and cautery: Effective but with recurrence risk.
  • Pulsed dye laser: Safe and effective for smaller lesions, particularly in children.
  • Sclerotherapy: Using monoethanolamine oleate for minimal scarring.
  • Surgical excision: Offers lower recurrence rates, especially in gingival lesions.

Prognosis

Pyogenic granulomas are benign and rarely resolve spontaneously, except in postpartum cases. Recurrence is common, particularly in gingival lesions or cases with persistent irritation or inadequate treatment. With appropriate intervention, the prognosis is excellent.

Written by: 

Naif Alshehri, Medical Intern. 

Resources: 

Dermnet

Bolognia Textbook 5th Edition

Definition 

Atopic eruption of pregnancy (AEP) is a pruritic skin condition associated with pregnancy, manifesting as eczematous or papular lesions in individuals with an atopic background. It often begins during early pregnancy, with 75% of cases occurring before the third trimester. AEP includes eczema in pregnancy, prurigo of pregnancy, and pruritic folliculitis of pregnancy, previously classified as separate conditions. While most cases involve new-onset atopic changes, some represent exacerbations of pre-existing atopic dermatitis. The disorder is not linked to adverse fetal outcomes and tends to recur in subsequent pregnancies.

Epidemiology

AEP is the most common pregnancy-related dermatosis, accounting for over 50% of such cases. Its exact incidence is unclear but may range from 1 in 5 to 1 in 20 pregnancies. It is more prevalent in individuals with a personal or family history of atopy, such as asthma, allergic rhinitis, or atopic dermatitis.

Etiology

AEP is linked to immunologic changes during pregnancy. Pregnancy is characterized by reduced T-helper 1 (Th1) cytokine production (e.g., IL-12, interferon-γ) and enhanced T-helper 2 (Th2) cytokine production (e.g., IL-4, IL-10). This shift toward a Th2-dominant immune response exacerbates the existing imbalance in atopic individuals, potentially triggering the development of AEP. While a connection to a history of atopy is recognized, its role remains debated.

Clinical Features

AEP typically manifests during the first or second trimester. About 80% of patients experience new-onset atopic changes, while 20% have a recurrence of pre-existing atopic dermatitis.

• Eczematous Lesions (E-Type AEP):

Most cases involve widespread eczematous eruptions affecting the face, neck, and flexural areas. These lesions may appear as patches or excoriated papules. Severe dryness and signs of atopy are common.

• Prurigo of Pregnancy (P-Type AEP):

Characterized by grouped erythematous papules or nodules on extensor surfaces, abdomen, and trunk, which may be excoriated or crusted. Lesions typically resolve postpartum.

• Pruritic Folliculitis:

Rare presentations involve follicular papulopustular eruptions resembling steroid-induced acne. These lesions, initially appearing on the abdomen, may spread and are mildly pruritic. They generally resolve within weeks postpartum.

Diagnosis

AEP is primarily diagnosed clinically, based on characteristic lesions and a history of atopy. Skin biopsy is rarely helpful due to nonspecific findings but may be performed if the diagnosis is uncertain or to rule out conditions like pemphigoid gestationis. Elevated serum IgE levels are seen in up to 70% of cases. Folliculitis should be cultured to exclude bacterial or fungal infections.

Management

The treatment of AEP focuses on symptom relief:

1. Topical Corticosteroids:

Low- to mid-potency corticosteroids are the first-line treatment for cutaneous lesions.

2. Emollients and Hydration:

Regular use of emollients helps maintain skin hydration.

3. Oral Antihistamines:

Chlorpheniramine, loratadine, or cetirizine can alleviate pruritus.

4. Other Topical Treatments:

Tacrolimus for sensitive areas (e.g., face, intertriginous zones), urea-based creams, and menthol-containing products are safe during pregnancy.

5. Severe Cases:

UVB therapy may be considered. Secondary bacterial infections should be treated with pregnancy-safe antibiotics like penicillins or cephalosporins.

Prognosis

AEP does not adversely affect the fetus and typically resolves postpartum, although symptoms may persist for a few weeks. The condition often recurs in subsequent pregnancies.

Written by: 

Raneem Alahmadi, Medical Intern.

Revised by:

 Naif Alshehri, Medical Intern

Resources:

Bologina 5th edition

UpToDate

Background

Leukonychia, or white nail, is defined as partial or complete whitening of the nail plate affecting one or more fingernails or toenails. The nail loses its natural pink color, taking on a white appearance. It can be classified according to the underlying pathology, its distribution, or its mode of onset.

Classification according to pathology

• True leukonychia: 
  • Due to abnormal nail plate keratinisation. 
  • The white nail will not be hidden by pressure application of the nail plate.

• Apparent leukonychia: 
  • Secondary to disease of the nail bed. 
  • Disappears with pressure application on the nail.

Classification according to distribution

Leukonychia can be partial or total.

• Total leukonychia: whitening of the entire nail plate.
• Partial leukonychia: 3 subtypes are described.
  • Punctate
  • Longitudinal
  • Striate

Classification by development timeline

White nails can be acquired or congenital.

• Congenital: Familial leukonychia is more commonly inherited recessively, although dominant patterns are possible
• Acquired: Secondary to systemic disease. 

Causes

• Trauma

• Poisoning and drugs

• • Heavy metal poisoning (eg lead, arsenic)
  • Chemotherapy
  • Sulphonamides

• Systemic illness

• • Liver cirrhosis
  • Chronic kidney disease
  • Heart failure
  • Hypoalbuminemia 
  • Protein-losing enteropathy
  • Diabetes
  • Iron deficiency (anaemia)
  • Zinc deficiency
  • Hyperthyroidism.

Diagnosis

History and physical examination are typically adequate.

The following can provide additional insight:

• Nail clippings to rule out fungal infections
• Nail biopsy
• Blood tests to evaluate systemic disease.

Treatment 

• Management varies based on the underlying cause.
• Trauma-induced leukonychia has no specific treatment.
• Punctate lesions will disappear as the nail follows its natural growth pattern.

Written by:

Dr. Renad Alkanaan

Revised By: 

Naif Alshehri, Medical Intern

Resources: 

Dermnet

UpToDate

What is Parakeratosis Pustulosa?

Parakeratosis pustulosa is a condition characterized by the deformation of the fingernail or toenail, accompanied by surrounding erythema and often scaling of the overlying skin. It predominantly affects the thumb or index fingernail in young children, although it can occasionally involve other digits, including toenails. The condition is approximately three times more prevalent in females.

Initial manifestations typically involve erythema beneath the free margin of the nail, which subsequently extends to the nail fold, resulting in swelling and the loss of the cuticle. As the condition progresses, thickened skin pushes upward, leading to deformities in the nail plate. Parakeratosis pustulosa is generally not pruritic, though it may cause mild pain .

 Causes

The exact cause of parakeratosis pustulosa is not fully understood. While it may be associated with various skin conditions, the specific mechanisms remain unclear in many cases.

Clinical features 

An affected nail may exhibit a variety of clinical signs, including:

• Subungual hyperkeratosis 
• Onycholysis
• Onychomadesis 
• Pitting 
• Transverse ridging 
• Ragged or absent cuticles
• Erythema of the periungual skin
• Blister formation on the fingertips

These signs can complicate the differentiation from other dermatological conditions, such as psoriasis and atopic dermatitis, leading to frequent misdiagnosis despite their common occurrence

Diagnosis

 Parakeratosis pustulosa is primarily a clinical diagnosis, with diagnostic investigations conducted to exclude other potential nail disorders.

• Swab cultures may aid in identifying microorganisms associated with paronychia.
• Tinea infection can be diagnosed through the detection of fungal hyphae in skin scrapings.
• Biopsy  can distinguish between atopic dermatitis and psoriasis, it is infrequently required in clinical practice.

Treatment

 There is no specific treatment for Parakeratosis pustulosa .However, most cases tend to improve gradually over time. The following treatments have been occasionally found to be beneficial:

• Emollients
• High-potency topical corticosteroids
• Topical retinoids
• Calcipotriol

The duration of lesions can vary, ranging from one week to several years, although recurrences are infrequent.                                                                     

Written by:

Atheer Alhuthaili, Medical Intern

Revised by:

Naif Alshehri, Medical Intern

References:

DermNet

Medscape

Definition

Pityriasis rosea is a self-limiting skin condition characterized by an initial “herald patch,” followed by a symmetrical rash of smaller scaly oval lesions, typically distributed along the trunk in a “Christmas tree” pattern. It primarily affects young adults, resolves within 6–10 weeks, and may be associated with a viral trigger, though its exact cause is unknown.

Epidemiology

This condition is most prevalent in healthy individuals aged 10–35, with a slight female predominance. Although it can occur in any season, some studies suggest increased incidence in spring, fall, or winter, depending on geographic location. It affects approximately 0.5% to 2% of the population worldwide and is rarely seen in children under two years old.

Etiology 

The exact cause of pityriasis rosea remains uncertain. A viral origin is widely hypothesized, with human herpesvirus types 6 and 7 (HHV-6/7) being the most strongly associated, though evidence is inconclusive. Other possible triggers include H1N1 influenza, SARS-CoV-2, and certain vaccines, such as COVID-19, smallpox, and hepatitis B. Drug-induced cases have also been reported, linked to medications like ACE inhibitors, NSAIDs, and antipsychotics.

Clinical Features

The hallmark of pityriasis rosea is the herald patch, which is a slightly raised, salmon-pink or red lesion 2–5 cm in diameter with a collarette of scaling at the margin. This is followed by the secondary rash, which appears as smaller oval plaques with similar scaling, distributed primarily on the trunk and upper extremities typically distributed along Langer lines in a “Christmas tree” pattern. The rash often spares the face, palms, and soles. In some cases, prodromal symptoms such as mild fever, headache, or malaise precede the rash. About 25% of patients experience pruritus, ranging from mild to severe.

Variants of the condition may involve atypical features, including inverse patterns affecting the axillae or groin, or more severe forms with pustules, vesicles, or purpuric lesions.

Diagnosis

Diagnosis is primarily clinical, based on the characteristic appearance and distribution of lesions. When uncertain, histology may confirm subacute dermatitis, particularly for drug-induced cases. It is essential to differentiate pityriasis rosea from other conditions, especially when atypical lesions or palm/sole involvement occurs.

Management

Treatment focuses on symptom control and patient reassurance, as the condition is self-resolving. Common interventions include:

• General measures: Using moisturizers, gentle bathing practices, and limited sun exposure.
• Topical treatments: Low to Medium-strength corticosteroids and antipruritic lotions to alleviate itching.
• Systemic treatments: Oral antihistamines for itching; acyclovir for faster lesion resolution in severe cases; and, in rare instances, oral corticosteroids or phototherapy. 

For pregnant women, caution is advised as pityriasis rosea may increase the risk of miscarriage during the first trimester if associated with active HHV-6 infection.

Written by: 

Raneem Alahmadi, Medical Intern

Revised by:

Naif Alshehri, Medical Intern

Resources:

Bolognia 5th edition

Dermnet