What is melanoma?

Melanoma is a serious type of skin cancer that affects melanocytes, which are pigment-producing cells that give skin its color. Melanoma is more likely to spread and invade other organs in the body, making it more dangerous and malignant than other forms of skin cancers.

How does melanoma develop?

Transformation of melanocytes to melanoma requires a complex interaction of various factors. The cells undergo histological changes and ultimately progress to malignant melanoma. The first change that occurs is the development of benign nevi, comprising mainly of neval melanocytes, a variant of normal melanocytes but slightly larger. Nevi can remain dormant and static for decades but with certain endogenous and exogenous factors, like genetic mutations in CDKN2A and BRAF, it can progress to malignancy.

Who gets melanoma and what are the risk factors?

The strongest risk factors for melanoma are UV light exposure, family history of melanoma, previous melanoma and sun sensitivity. It affects mainly white population with fair skin, and the highest reported rate are in Australia and New Zealand. Melanoma occurs most commonly between the age of 40 to 60 years, however there has been an increase in incidence in young adults around the age of 20. The occurrence is extremely rare in children. 

What are the clinical features of melanoma?

Melanocytes are found throughout the body, thereby melanoma can be present anywhere on the body, not necessarily in areas with a lot of sun exposure. It begins as a mole or freckle, frequently on the back in males and lower extremities in females, but clinical presentation varies depending on the type.

Melanoma subtypes

There are four main types of melanoma that are associated with the same growth pattern, i.e horizontal, and anatomical site predilection.

Superficial spreading melanoma

Most common type, associated with intermittent UV exposure. It can appear on an existing mole or a new mole. It is likely found on the torso in men and legs of women.

Lentigo malinga

Occurs in chronically sun-exposed individuals and it is easily detected by simple visual inspection.

Nodular melanoma

This type is rapid growing and aggressive.

Acral and mucosal melanoma

Most common type of melanoma in Asian and African population. This type is not associated with UV radiation. 

Melanoma comes in many shapes, sizes and colors. Clinical diagnosis is primarily based on patient history total-body skin examination. Early detection and prevention are key in curing and preventing melanoma; applying sunscreen and UV radiation avoidance (staying indoor, avoiding tanning bed) may prevent the development of melanoma.

Written by: Naif Alalshaikh, Medical student. 

References 

1. “Melanoma.” DermNet
2. Miller, Arlo J., and Author AffiliationsFrom the Dermatopathology Unit. “Melanoma: Nejm.” New England Journal of Medicine, 28 Sept. 2006,
3. “Melanoma.” The Skin Cancer Foundation, 28 Apr. 2022,
4. Melanoma – Edisciplinas.usp.br.

Xeroderma pigmentosum (XP) is a rare autosomal recessive DNA repair disorder characterized by enhanced UVR sensitivity, early pigmentary alterations, UVR-induced skin and mucous membrane malignancies, and, in some cases, progressive dementia. Moritz Kaposi, a dermatologist, first reported XP in 1874, coining the word “xeroderma” to describe the dry or xerotic skin quality of his four XP patients. While early research suggested that UVR played a role in the disease’s development, it wasn’t until 1968 that the sickness was linked to faulty DNA repair in cultured skin fibroblasts. XP subtypes or “complementation groups” were discovered as a result of this; XP-variant is the only form of XP with intact DNA excision repair capacity.

Males and females are equally affected by Xeroderma pigmentosum (XP), which is found worldwide but has a wide range of occurrence. The estimated incidence in the United States and Western Europe is one per million live births, according to retrospective investigations. Incidences as high as 15 to 20 per million in Libya and 10 to 50 per million in Japan have been reported in other research. Due to more frequent consanguineous marriages, incidences in Northern African and Western Asian nations such as Libya, Tunisia, Morocco, and Pakistan may be greater. Consanguinity, on the other hand, isn’t thought to account for all of the global differences.

Early-onset pigmentary skin alterations, early development of skin malignancies (typically in the first decade of life), and ocular signs, such as photophobia, conspicuous conjunctival injection, and severe keratitis, are all common features across all xeroderma pigmentosum (XP) groups. Neurologic diseases, such as sensorineural hearing loss and gradual cognitive impairment, are seen in certain patients.

Skin cancer — Squamous cell cancer (SCC), basal cell carcinoma (BCC), and melanoma all occur more frequently in XP than in the general population, and at a younger age. The odds of nonmelanoma skin cancer (NMSC) and melanoma were shown to be 10,000-fold and 2000-fold greater in a 40-year National Institutes of Health follow-up study of 106 XP patients, respectively, than in the general population.

Skin cancer is the most prevalent type of cancer connected with XP, although multiple studies suggest that XP patients may be at an increased risk of other malignancies as well. In 142 consanguineous French families of North African origin with an XPC mutation, an increased frequency of hematologic malignancies, such as myelodysplastic syndrome, acute myeloid leukemia, and acute lymphoblastic leukemia, was observed. Colorectal cancer susceptibility has been linked to XPG single nucleotide polymorphisms, particularly among Asians. In nonsmoking Chinese female patients, XPD polymorphisms were found to be associated with the risk of non-small cell lung cancer.

A child with acute sun sensitivity with minimum exposure, early and prominent freckling (before the age of two years), and skin cancer within the first decade of life should be suspected of having xeroderma pigmentosum (XP). Photophobia with conspicuous conjunctival injection, severe keratitis, sensorineural hearing loss, and increasing cognitive impairment are other clinical symptoms that point to the diagnosis. Clinical symptoms, a family history consistent with autosomal recessive inheritance, and/or confirmatory genetic tests are used to make the diagnosis.

Dermatologists, ophthalmologists, oral surgeons, geneticists, and neurologists are part of a multidisciplinary team that treats individuals with xeroderma pigmentosum (XP). The pillars of treatment are strict sun protection and avoidance, diligent clinical follow-up with regular skin and eye examinations, and appropriate and early treatments of any premalignant or malignant skin lesions.

Patients with xeroderma pigmentosum (XP) die most often from metastatic skin cancer, followed by neurodegeneration. Patients with neurodegeneration die at a significantly younger age than patients without neurodegeneration, with a median age of 29 versus 37 years.

Written by: Lama Altamimi, medical intern.

Reference: https://www.uptodate.com/contents/xeroderma-pigmentosum?search=xeroderma%20pigmentosum&topicRef=3004&source=see_link

Papillon-Lefèvre syndrome (PLS) is a rare genetic condition that affects children between the ages of one and five. It is inherited in an autosomal recessive manner. It results from alterations of the CTSC gene; which regulates the production of cathepsin C enzyme. PLS is characterized by the appearance of hyperkeratotic patches on the palms and soles, as well as severe inflammation and deterioration of the structures that surround and support the teeth (periodontium). 

Clinical Presentation: 

Oral features: 

Severe gingivostomatitis and periodontitis are the most common symptoms of PLS. In patients suffering from PLS, deciduous teeth erupt in the expected order, with normal structure and shape, at the appropriate ages. However, gingiva becomes inflamed during the first year after the eruption of deciduous teeth, followed by fast periodontal deterioration evidenced by visible reddish and swollen gingiva, severe bone resorption, and deep periodontal pockets out of which pus exudates in response to minimal pressure. Due of the hypermobility of the teeth, mastication is quite uncomfortable in those patients. A foul smelling mouth odor is usually present. Around the age of 4-5 years, the child’s deciduous teeth fall out prematurely, and the child becomes entirely edentulous, with gingiva returning to its normal status. Nevertheless, with the eruption of permanent or successor teeth, periodontitis occur again. By early adolescence, the majority of the successor teeth will fall out.

Cutaneous features: 

PLS is marked by the appearance of dry, scaly patches of skin (hyperkeratosis) in children between the ages of one and five; it is manifested simultaneously with oral manifestations. These patches most commonly affect the palmar aspect of the hands and the plantar aspect of the feet –although they can also affect the knees and elbows. The skin of those who are affected can be abnormally red and thick, but it can also vary in texture and color. Skin lesions may worsen in cold weather, making walking extremely difficult. 

Management: 

A multidisciplinary approach involving a team of a dermatologist, a pediatrician and a dentist is crucial for patients with PLS. Moreover, emollients and salicylic acid are used to treat the cutaneous manifestations of PLS; topical steroids may be used to enhance their effectiveness. Oral retinoids including acitretin, etretinate, and isotretinoin have been shown to help with both oral and cutaneous PLS lesions.

Written by: Rema Aldihan, Medical Student.

References: 

rarediseases.org

www.ncbi.nlm.nih.gov/pmc/articles/PMC4507741/

Hemangioma is the most common benign vascular tumor of infancy. It is more common among baby girls than boys (3:1). Low birth-weight, advanced maternal age, multiple pregnancy (twins and triplets), placenta previa and preeclampsia are all risk factors for developing infantile hemangioma. It is believed that the expression of GLUT1 protein in utero is the placental origin for infantile hemangioma. 

Most hemangiomas don’t occur at birth but appear within the first two weeks of life, most commonly on the head and neck area. It usually starts off as a red spot resembling a scratch, but instead of fading away, it gradually grows. Most infantile hemangiomas grow very rapidly in the first 3 months, they tend to have a growth arrest by 5 months of age, and recede over the next couple of years.  Hemangiomas could be superficial or deep; superficial hemangioma appear bright red, while deep hemangioma appear bluish-purple in color. The majority of hemangiomas are focal, but could occasionally present as segmental or multifocal. 

Hemangioma could arise on its own or as a part of PHACES Syndrome, which was first described by Dr. Ilona Freidan in 1996. It is a syndrome that includes infantile haemangiomas and malformation of eyes, heart, arteries and brain. The acronym PHACES stands for: Posterior fossa abnormalities, Hemangioma, Arterial abnormalities, Cardiac abnormalities, Eye and Endocrine abnormalities and Sternal clefts. 

Segmental haemangioma is more likely to be associated with PHACES syndrome when compared to focal haemangiomas. Moreover, the specific site of the segment affected by hemangioma can indicate the likely problem associated with it. For example, frontotemporal segments are associated with brain malformations, and mandibular segments are associated with cardiac anomalies and airway hemangiomas. 

Infants with hemangiomas larger than 24 cm on the face or scalp should undergo investigations to screen them for PHACES syndrome. Investigations include MRI, MRA, CTA, Eye examinations, ear examinations, audiometric testing, echocardiogram and U/S for blood vessels. 

The management of PHACES syndrome is tailored to each child depending on the involved organs. Careful evaluation of major blood vessels in the brain and heart should be undertaken prior to initiating propranolol. 

Written by: Rema Aldihan, medical student.

References:

https://www.ccakids.org/assets/syndromebk_hemangiomas.pdf

The most prevalent of the ichthyoses is ichthyosis vulgaris, a heterogeneous collection of inherited keratinization disorders characterized by extensive scaling of the skin of different severity. Pathogenic mutations in the filaggrin gene (FLG), which encodes profilaggrin, a key component of the keratohyalin granules in the epidermis’ granular layer, cause IV. Individuals who inherit a single mutant allele are substantially less seriously impacted than those who acquire homozygous or compound heterozygous mutations, indicating that the IV inheritance pattern is semidominant.

Clinical presentation:
The condition appears as widespread, dry skin with thin, white or gray scales on the extensor extremities and trunk in infancy or early childhood. Associated characteristics include hyperlinear palms and keratosis pilaris. Extensor extremities and the trunk are usually afflicted, with intertriginous (e.g., axillary, antecubital, and popliteal) skin remaining unaffected. It’s unusual for the sides of the neck to be involved. Scaling has a range of severity. Individuals who have only one mutant allele (heterozygotes) have a modest phenotype that can be mistaken for simple dry skin, whereas individuals who have mutations in both alleles (homozygous or compound heterozygotes) have a more obvious condition. The severity of the condition varies dramatically by season, improving in warm and bright weather with high ambient humidity and deteriorating in dry and cold conditions.

Diagnosis:
The clinical diagnosis of ichthyosis vulgaris (IV) is based on the patient’s personal and family history, as well as clinical findings on physical examination. Although individuals with homozygote or compound heterozygote variations of the filaggrin gene (FLG) who have a more severe phenotype may find it easier to diagnose, heterozygotes, who normally have a very mild symptom, may find it more difficult.

The following clinical signs and symptoms point to an IV diagnosis:

• Scale: Fine, white or gray, central attachment; extensor surface of extremities and trunk involved; folds spared.
• Palmar hyperlinearity: Major fissures are exaggerated, minor fissures are increased, and lines on the thenar eminence are accentuated.
• Keratosis pilaris.

The following are examples of personal and family history that support the diagnosis of IV:

• Symptoms appear shortly after birth, and are most common in early childhood.
• Warm weather and emollients make a difference.
• With age, there may be an improvement.
• Atopic eczema or other atopic illnesses are linked.
• Occurrence in the family

A skin sample with hematoxylin and eosin staining that shows a marked decrease or absence of the granular layer in the epidermis can assist confirm the diagnosis of IV. Biopsies are best performed on the extensor side of the arm or the shin. Electron microscopy can confirm keratohyalin granule abnormalities, despite the fact that it is rarely utilized for routine skin diagnosis.

Genetic testing – Although not regularly done in clinical practice, genetic testing demonstrating pathogenic mutations in the FLG gene offers the definite diagnosis of IV. Although variants differ within populations, and identification of “private” variants is difficult and may be overlooked unless Sanger sequencing or an equivalently comprehensive examination of the complete gene is performed, common population relationships may be beneficial for screening.

Treatment:
The goal of ichthyosis vulgaris (IV) treatment is to remove scales, reduce skin dryness, and improve the appearance of the skin. It entails regular bathing and the use of moisturizers and keratolytics.

1- Bathing – People with dry skin, especially those with IV, are frequently advised to take long baths to help remove scale. Although only a few studies back it up, this advice is basic sense and has lasted the test of time. The value of bath additives such as oils and sodium bicarbonate is debatable. After bathing, moisturizers should be applied, whether or not soaps or synthetic detergents were used.

2- Emollients and moisturizers — The mainstay of IV treatment is frequent and generous application of emollients and moisturizers. Moisturizers keep the skin hydrated and smooth. Humectants like glycerin, occlusives like petrolatum, emollients like cetyl alcohol, keratolytics like urea and alpha-hydroxy acids, and other ingredients are included. Occlusives, which are water insoluble but have a lower molecular weight than occlusives, prevent water loss; emollients, which are water insoluble but have a lower molecular weight than occlusives, smooth the skin; and keratolytics help remove scale.

3- In the therapy of IV, topical retinoids, steroids, calcipotriene, and systemic retinoids are not recommended. The treatment of atopic dermatitis is covered in another article.

Prognosis:
Individuals with ichthyosis vulgaris (IV) live normal lives with no known shortening of life expectancy, but they must cope with the daily treatment of scaling skin disease, which is frequently associated with moderate to severe atopic dermatitis. In the ichthyoses, quality-of-life studies have focused on the more severe conditions, but none have addressed IV.

The majority of people with ichthyosis want to learn more about their condition and how to best treat it. They usually have a better understanding of what works for their skin once they have this information, and they rarely seek medical help until they have a problem. This is especially true in IV, where eczema causes the most therapeutic problems and consequences.

Written by: Lama Altamimi, Medical intern.

Reference:

UptToDate

Rosacea is a skin disease that causes erythema to form across the nose and cheeks. In addition to medical therapy, rosacea patients can improve their remission by identifying and avoiding common environmental factors that may trigger flare-ups or aggravate their conditions. Below are the lists on how to prevent the rosacea to flare-ups:

 sun protection:

sun exposure is the most common trigger, and should be avoided by applying a broad-spectrum sunscreen with an SPF of 30 or higher. In addition, it is better to use fragrance-free sunscreen containing zinc oxide and titanium dioxide because they are less likely to cause skin irritation. Moreover, wearing a hat when exposed the sun is essential to protect the face and neck. 

 Avoid stress:

Emotional stress accounts for 79% of rosacea flare-ups; try to do activities that relieve your stress, such as yoga classes, and joining support groups. Minimize eating spicy food/ food and beverages that are high in temperature; one can drink iced coffee or tea instead, or let hot beverages warm a bit.

 Review medications:

There are some medications known to trigger rosacea, like antihypertensives and vitamins, that has to be reviewed by the treating physician.

 Reduce Exercising in a hot climate:

Exercising will increase the body temperature, and that will worsen the condition. This can be avoided by doing less intense exercise and doing it indoors.

 Makeup precautions:

Using a mild, fragrance-free emollient to the skin before applying makeup can help prevent flares. Avoiding waterproof makeup or heavy foundations is vital to avoid flare-ups.

Select specific skin and hair care products:

 Protect the face from cold wind

Written by: Dr. Nouf Aljomah, dermatology resident

References:

American Academy of dermatology

https://www.nhs.uk/