A severe genetic variant of ichthyosis called harlequin ichthyosis manifests at birth as thicker, rigid skin plates that cover the entire body like armor. The condition is uncommon and equally affects men and women. Approximately one in 300,000 neonates are affected by it. Harlequin ichthyosis is not known to be racially predisposed. There could be a higher occurrence in societies where paternal consanguinity is prevalent.

 

Causes:

Harlequin ichthyosis is inherited in an autosomal recessive manner. The ABCA 12 gene alterations are to blame. It is thought that the ABCA12 gene encodes a transporter protein that is necessary for healthy skin development and is involved in the movement of epidermal lipids across cell membranes. The cell cannot produce any ABCA12 protein due to certain mutations in the ABCA12 gene. Additional mutations result in the synthesis of an atypically tiny protein that is incapable of carrying lipids in an appropriate manner. Harlequin ichthyosis is characterized by hard, thick scales that are caused by a disruption in the normal development of the epidermis caused by a loss of functional ABCA12 protein.

 

Clinical features:

The clinical features include skin changes present at birth, significantly thickened, with deep erythematous fissures separating the scales and huge, glossy plates of hyperkeratotic scale. Facial features include degraded nasal alae and blocked nares. The external auditory canal may be blocked by scale, and the ears’ pinnae and retroauricular folds may be tiny or nonexistent. The lips’ traction results in eclabium.

 

Diagnosis:

Genetic laboratory testing and a physical examination of the patient are necessary for the diagnosis of harlequin ichthyosis. The most precise diagnostic procedure for harlequin ichthyosis involves looking for a loss of function mutation in the ABCA12 gene using genetic testing. Gene mutations may result in smaller versions of the proteins essential for skin development as well as poor lipid transport in the skin. A collodion membrane and congenital ichthyosiform erythroderma-like appearance are the outcomes of less severe mutations. Histology of the skin biopsy reveals hypergranulosis, parakeratosis, and a significantly thicker stratum corneum.

 

Management:

Treatment for harlequin ichthyosis focuses on skin protection and infection control; there is no known cure. For several weeks during their early years, the majority of harlequin babies require one-on-one nursing care. Infection prevention or treatment during this period may also require antibiotics. After bathing, when the skin is still damp, softening emollients especially those that contain urea, salicylic acid, or alpha hydroxy acids work exceptionally well. These products help to maintain the skin’s suppleness and moisture content while guarding against the fissures and cracks that can result in a subsequent bacterial infection. It has also been demonstrated that early systemic treatment with oral retinoids (such as acitretin or isotretinoin) improves overall survival, softens, or resolves plate-like scales, and heals skin fissures.

 

Complications: 

Poor immunity, infections, muscle shortening, limb necrosis and amputation, and respiratory failure.

 

Outcome:  

Infants with harlequin ichthyosis in the past hardly made it past the first few days of life. The survival rate has increased due to innovations in newborn care; globally, rates are getting close to 50%.  Youngsters who make it through the neonatal stage typically acquire a less severe form of ichthyosis, but they still exhibit fish-scale scales, seborrheic patches that retain waxy, yellowish material, generalized poor hair growth, and scarring alopecia.  Those who survive harlequin ichthyosis may nevertheless experience hypothyroidism, small stature, arthralgias, digit contractures, and failure to flourish.   

 

Written by:

Mohammed Alahmadi, Medical Student. 

Revised by:

Maee Barakeh, Medical Student. 

References:

DermNet

Dermatology by Bolognia

Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology

Image source: Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology 

 

Nodular prurigo (NP), also known as prurigo nodularis, is a chronic dermatological disorder characterized by intensely pruritic, firm nodules. Although it can form anywhere on the body, a symmetrical distribution of arms, legs, back, and torso is where it most frequently appears.

 

Etiology:

It is still unclear what specifically causes NP. Based on skin biopsies, it is believed to be related to a dysregulation of the nerves, with more nerve cells seen in the dermis and fewer in the epidermis. 

There is also an association with atopy, certain drugs, and systemic conditions such as chronic kidney disease, liver disease, diabetes, and malignancy.

 

Clinical features:

The severity of NP can range from a few to hundreds of lesions of different sizes.

At first, the rash:

– Include tiny, red, or pink bumps typically 3–8 mm in diameter.

– Has a hyperpigmented border

– Very itchy 

– Is distributed in readily accessible body regions, including the lateral aspects of the arms and legs, shoulders, chest, and buttocks.

Sometimes, it begins as a papule and progresses to a nodule or plaque.

Scratching results in:

-Enlargement producing a raised, warty, nodular surface. The nodules have a symmetrical distribution and are usually hard and small, but they can reach up to 3 cm in diameter.

-Ulceration of the skin that can lead to an increased risk of infection.

-Healed lesions may leave a scar or discoloration.

 

Diagnosis:

The diagnosis of NP is clinical, based upon the clinical presentation of distinctive excoriated, nodular lesions frequently distributed symmetrically and a patient’s history of persistent, intense pruritus. A skin biopsy is not routinely performed to confirm the diagnosis.

It is essential to evaluate systemic causes of persistent pruritus in individuals with NP who do not have a history of atopic dermatitis or other pruritic skin disorders. These causes may include chronic kidney disease, liver disease, thyroid disease, HIV infection, parasite infestation, or malignancy. The initial laboratory and imaging evaluation may consist of:

• Complete blood cell count
• Liver function tests
• Blood urea nitrogen and creatinine
• Thyroid-stimulating hormone
• HIV test
• Urinalysis
• Stool examination for ova and parasites
• Chest radiograph

 

Management:

A complex and multi-modal strategy is necessary for the treatment of NP which includes:

• Instructing patients on various ways to reduce skin itching and scratching 
• Treating pruritus symptoms 
• Topical or systemic therapies that target the itch-scratch cycle and minimize skin lesions

Common treatment options include: 

• Topical emollients
• Topical steroid cream or ointment — usually ultrapotent steroid and applied under hydrocolloid dressing or paste bandage occlusion, or steroid impregnated tape
• Topical capsaicin and tacrolimus 0.1% ointment for itch
• Local corticosteroid injection into the nodules to reduce inflammation
• Sedating oral antihistamines
• Phototherapy with either UVB or photochemotherapy (PUVA)
• Systemic treatment with gabapentin, pregabalin, and naltrexone
• Occasionally, antibiotics may be used to treat locally infected skin (cellulitis).

 

Written by:

Mashael Alanazi, Medical student.

Revised by:

Maee Barakeh, Medical student.

References:

DermNet

Uptodate

Keratoacanthoma (KA) is a commonly encountered skin tumor that presents a captivating clinical challenge due to its rapid growth and locally destructive nature. While some cases of KA may regress spontaneously, they often leave behind visible scarring. However, the clinical presentation of KA can closely resemble well-differentiated squamous cell carcinoma (SCC), leading to unpredictability in its course.

Pathophysiology:

The precise pathophysiological mechanisms underlying keratoacanthoma are not fully understood. However, it is widely believed to arise from the hair follicles or the sebaceous glands. Several hypotheses have been proposed, including the role of ultraviolet radiation, genetic factors, viral infections, and immune dysregulation in the development of keratoacanthoma.

Clinical Features:

Keratoacanthoma typically presents as a rapidly growing dome-shaped nodule with a central crater filled with keratin debris. It commonly occurs on sun-exposed areas of the body, such as the face, scalp, ears, and dorsum of the hands. Initially, the lesion may resemble a pimple or a wart, but it rapidly enlarges over a period of weeks to months. The growth phase is followed by a stabilization phase, during which the lesion may persist for several months before spontaneously regressing.

Diagnosis:

The diagnosis of keratoacanthoma is primarily based on clinical examination and histopathological evaluation. A thorough physical examination, including a dermatoscopic assessment, can aid in distinguishing keratoacanthoma from other skin lesions. Dermoscopy often reveals a central plug, keratin-filled crater, and peripheral keratotic rim. To confirm the diagnosis, a skin biopsy is performed, and the specimen is sent for histopathological analysis. Microscopically, keratoacanthoma is characterized by a well-demarcated cup-shaped lesion with a central keratin-filled crater, hyperkeratosis, and proliferation of keratinocytes.

Management:

The management of keratoacanthoma depends on various factors, including the size, location, and individual patient characteristics. Several treatment options are available, and the choice of therapy should be tailored to the specific case. Here are some commonly employed management strategies:

1. Observation: In some cases, keratoacanthomas may undergo spontaneous regression without any intervention. Close observation with regular follow-up visits may be appropriate for small, asymptomatic lesions in low-risk areas.

2. Surgical Excision: Surgical excision is a commonly employed treatment modality for keratoacanthoma. It involves complete removal of the lesion with a margin of healthy tissue to reduce the risk of recurrence. This approach is particularly suitable for larger or symptomatic tumors.

3. Mohs Micrographic Surgery: Mohs surgery is a specialized technique that ensures the highest cure rate while preserving as much healthy tissue as possible. It is often recommended for lesions in cosmetically sensitive areas or those with aggressive features.

4. Topical Therapies: In select cases, topical treatments such as imiquimod cream or 5-fluorouracil may be employed. These medications stimulate the immune system or inhibit cell proliferation, leading to tumor regression.

5. Cryotherapy: Cryotherapy involves freezing the lesion with liquid nitrogen. It is commonly utilized for smaller keratoacanthomas and can be performed in an outpatient setting.

Written by:

Deemah AlHuraish, medical student.

Revised by:

Maee Barakeh, medical student.

References:
DermNet

NCBI

AOCD

Merkel Cell Carcinoma, also known as cutaneous neuroendocrine carcinoma, is a rare and aggressive form of skin cancer with a high risk for recurring and metastasizing. It occurs almost exclusively in white skin, and is slightly more common in males.

Etiology:

Approximately 80% of examined Merkel cell carcinomas have Merkel cell polyomavirus (MCPyV) identified. It is believed that when immune function is compromised, the virus induces gene alterations that result in Merkel cell cancer.

Because virus-negative tumors typically develop on skin that has been exposed to the sun, they are linked to high UV radiation exposure. One major contributing factor to the development of Merkel cell carcinomas is immunosuppression.

It was once thought that Merkel cells, which are skin pressure receptors, were the source of Merkel cell cancer. Based on clonal immunoglobulin chain rearrangement, early B-cell markers expressed, and cellular shape, a new study suggests that their ancestors were lymphocytes.  

Clinical features:

Typically, asymptomatic, non-tender, solitary, uneven red nodule that is rapidly growing is the first sign of Merkel cell cancer. Although it grows far more quickly, it frequently resembles other, more prevalent skin malignancies in appearance, such as basal cell carcinoma.

Multiple metastases may form surrounding the primary tumor in Merkel cell tumors, which spread through the lymphatic system and can cause a local recurrence. Additionally, it may spread to axillae, groin, and neck lymph nodes.

The rate of recurrence  is markedly higher than that for invasive melanoma, squamous cell carcinoma, or basal cell carcinoma. The majority of recurrences happen in the first two years following diagnosis.

Diagnosis:

Any tumor exhibiting the following clinical characteristics, which are seen in roughly 90% of patients, should be ruled out as being likely to be Merkel cell carcinoma. These characteristics can be remembered using the acronym “AEIOU”:

• Asymptomatic or non-tender
• Expanding rapidly
• Immune suppressed
• Older than 50
• UV-exposed fair skin

A tumor biopsy is the primary test. This demonstrates the typical histology of Merkel cell cancer. Since thyroid transcription factor (TTF1) is typically negative and cytokeratin-20 (CK20) is positive in up to 95% of tumors, immunohistochemistry can be useful.

If the tumor has progressed to other places, a general examination, including assessment of the local lymph nodes, and staging studies may be scheduled. Imaging modalities, lymph mode ultrasound scanning, and sentinel node biopsies are examples of staging investigations. 

Management:

Treatment options include excision or Mohs surgery.  Except in very small lesions, radiation therapy is usually administered to the Merkel cell carcinoma site along with regional lymph node placement.

Pembrolizumab and nivolumab, immune checkpoint inhibitors for advanced Merkel cell carcinoma, up to 50% of patients have shown positive response. Avelumab, another PD-1/PD-L1 medication, received expedited approval from the US Food and Drug Administration in March 2017 to treat metastatic Merkel cell carcinoma.

Prognosis: 

Five-year survival rates are overall 30–50%. Survival rates are better for patients initially diagnosed with Stage 1 Merkel cell carcinoma and in younger patients than when it has already metastasized or patients are over 80 years of age. 

Written by:

Mohammed Alahmadi, Medical Student. 

Revised by:

Maee Barakeh, Medical Student. 

References:

DermNet

Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology

Review of Dermatology by Ali Alikhan

Acrodermatitis enteropathica (AE) is a rare genetic disorder characterized by impaired zinc absorption, resulting in zinc deficiency. This condition affects the skin, gastrointestinal system, and immune system.

 

Pathophysiology:

Acrodermatitis enteropathica is primarily caused by mutations in the SLC39A4 gene, which encodes for the zinc transporter protein known as ZIP4. This protein plays a crucial role in facilitating the absorption of dietary zinc from the intestines into the bloodstream. Mutations in the SLC39A4 gene lead to impaired zinc uptake, resulting in zinc deficiency despite an adequate zinc intake.

 

Clinical Features:

Clinical manifestations usually appear within 1 to 2 weeks after weaning or at 4 to 10 weeks of age if bottle-fed.

Acrodermatitis enteropathica is characterized by a classic triad of symptoms, including periorificial dermatitis, diarrhea, and alopecia. 

1. Periorificial Dermatitis:

The rash in acrodermatitis enteropathica typically presents with a distinct distribution. The periorificial rash is commonly observed in a horse-shoe or U-shaped pattern, involving the areas around the mouth and eyes, while sparing the lips. There is usually a sharp demarcation between the affected area and normal skin, creating a noticeable contrast. The rash may manifest as eczematous or psoriasiform plaques that can progress to include vesicles, bullae, pustules, erosions, or hyperkeratotic areas.

2. Diarrhea:

Diarrhea is a common symptom in acrodermatitis enteropathica and is often chronic in nature. 

3. Alopecia:

Another characteristic feature of acrodermatitis enteropathica is diffuse hair loss, which affects the scalp, eyebrows, and eyelashes. The hair loss may be patchy or diffuse and is attributed to the disruption of hair follicle development and maintenance due to zinc deficiency.

 

In addition to the triad, acrodermatitis enteropathica can present with various additional cutaneous manifestations. These include glossitis, characterized by a red and glossy tongue, along with mouth ulcers and angular cheilitis. Symmetrical peri-anal excoriations and a rash on the buttocks can also occur. Zinc deficiency can impair wound healing, resulting in delayed healing of cuts and abrasions. Nail changes, such as softness, ridging, abnormal growth, and inflammation of the nail fold (paronychia), may also be observed.

While the noncutaneous symptoms of acrodermatitis enteropathica include blepharo-conjunctivitis, sensitivity to light, loss of appetite, irritability, depressed mood, growth failure in untreated children, hypogeusia, and hypogonadism in male adolescents and young adults.

 

Diagnosis:

The diagnosis of acrodermatitis enteropathica is primarily based on clinical features and confirmed by laboratory tests. A thorough physical examination, including a detailed evaluation of the skin and mucous membranes, can provide valuable diagnostic clues. Additionally, a detailed medical history, including feeding patterns and response to zinc supplementation, is essential.

Laboratory investigations play a crucial role in confirming the diagnosis. Blood tests can reveal low serum zinc levels, which is a strong indicator of zinc deficiency.

 

Management:

The management of acrodermatitis enteropathica involves lifelong zinc supplementation to correct the underlying deficiency. Zinc supplementation can be administered orally or, in severe cases, intravenously. The dosage and duration of zinc supplementation are individualized based on the severity of symptoms and response to treatment.

In addition to zinc supplementation, it is essential to address any associated complications. This may include the treatment of skin infections, nutritional support to correct deficiencies of other nutrients, and management of gastrointestinal symptoms such as diarrhea and vomiting.

In conclusion, acrodermatitis enteropathica is a rare genetic disorder characterized by impaired zinc absorption and resulting in zinc deficiency. It presents with a triad of symptoms involving the skin, gastrointestinal system, and immune system. Early diagnosis and lifelong zinc supplementation are crucial in the management of this condition to prevent complications and improve overall health outcomes for affected individuals.

 

 

Written by:

Deemah AlHuraish, Medical Student.

Revised by:

Maee Barakeh, Medical Student.

 

References:

DermNet.

NCBI.

Bolognia Textbook of Dermatology.

PAPA syndrome, also known as Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne syndrome, is a rare autoinflammatory disorder characterized by a triad of symptoms: pyogenic arthritis, pyoderma gangrenosum, and severe acne. 

Pathophysiology:

The exact pathophysiology of PAPA syndrome is not yet fully understood. However, it is believed to be an autosomal dominant disorder caused by mutations in the PSTPIP1 gene, which is involved in regulating the immune system and inflammatory responses. The mutations lead to dysregulated production of pro-inflammatory cytokines, primarily interleukin-1 beta (IL-1β), resulting in chronic inflammation and tissue damage.

Clinical and Distinctive Features:

PAPA syndrome typically manifests in childhood or adolescence, although adult-onset cases have also been reported. The clinical features of PAPA syndrome include:

1. Pyogenic Arthritis: Recurrent episodes of painful joint inflammation, particularly affecting large joints such as the knees, hips, and ankles. These episodes are characterized by swelling, warmth, and limited range of motion.

2. Pyoderma Gangrenosum: Painful skin ulcers that develop in various areas of the body, most commonly on the lower extremities. These ulcers begin as pustules and progress to deep, necrotic wounds with undermined borders.

3. Severe Acne: Persistent and severe acne, nodulocystic type, that is resistant to conventional treatments. It often involves the face, chest, and back, and can lead to scarring.

Diagnosis:

Diagnosing PAPA syndrome can be challenging due to its rarity and overlapping symptoms with other conditions. However, a comprehensive evaluation including a detailed medical history, physical examination, and laboratory tests can aid in the diagnosis. Key diagnostic criteria include the presence of the characteristic triad of symptoms and genetic testing to identify mutations in the PSTPIP1 gene.

Management:

The management of PAPA syndrome focuses on controlling symptoms, reducing inflammation, and preventing complications. Also, it involves a variety of approaches depending on the dominant manifestation:

Arthritis:

– Arthritis episodes often respond well to oral or intra-articular corticosteroids.

– In cases where corticosteroids are not satisfactory or arthritis recurs frequently, long-term corticosteroid use may be necessary, despite potential side effects.

Pyoderma Gangrenosum:

– Pyoderma gangrenosum may show some response to oral corticosteroids.

– Local immunosuppressant and anti-inflammatory drugs in the form of creams are commonly used.

– Treatment response is usually slow, but new biologic drugs targeting IL-1 or TNF have demonstrated efficacy in individual cases.

Acne:

– Acne treatment in PAPA syndrome may involve oral tetracycline antibiotics or isotretinoin, depending on the severity of the condition.

Developments in Treatment:

– Biological response modifiers, which target inflammatory proteins (cytokines), have shown success in managing other inflammatory conditions and are being explored for PAPA syndrome.

– Treatments targeting tumor necrosis factor (TNF) such as infliximab, etanercept, and adalimumab, as well as those targeting interleukin 1 (anakinra), have shown positive responses in cases of resistant arthritis and pyoderma gangrenosum.

Written by:

Deemah AlHuraish, medical student.

Revised by:

Maee Barakeh, medical student.

References:

DermNet

NCBI