5th June 2025

Hypopigmentation

Vitiligo 

Vitiligo is an acquired disorder where there is complete depigmentation of affected skin due to loss of melanocytes and a chalky-white appearance of affected skin. It is an autoimmune disease and is associated with other such diseases. Lesions can occur in a focal or generalised distribution and can coalesce into almost complete depigmented areas.  It is often dismissed as a cosmetic issue due to the contrast between depigmented skin and normal skin, especially in dark skinned individuals. However, the disease can be psychologically devastating and those with vitiligo experience stigmatisation, social isolation and low self-esteem.

Cause 

The selective loss of melanocyte functioning in the epidermis causes the depigmented skin seen in Vitiligo. The exact mechanism for the destruction of melanocytes is not known but likely to be a multifactorial polygenic disease, with autoimmune responses (T-cell mediated destruction), oxidative stress, generation of inflammatory mediators, and melanocyte detachment mechanisms playing a role, depending on the disease subtype. 

Possible triggers for vitiligo have been identified and include emotional stress or illness, chemical exposure (phenolic/catecholic derivative in deodorant, oils, hair dye, disinfectants) and hormonal changes such as childbirth. The Koebner phenomenon where depigmentation occurs at a site of skin injury such as cuts, sunburn or abrasion is also a proposed trigger.

Prevalence 

Vitiligo is known to be the most common depigmenting skin condition and onset increases through the first two decades of life. However, it is uncommon in children less than 2 years of age.

Classification 

There are two main types of vitiligo: non segmental vitiligo and segmental vitiligo. Non segmental vitiligo is more common and roughly 90% of people with the condition have this. The different forms of non-segmental vitiligo include focal, mucosal, acrofacial, generalised and universal. Usually, depigmented lesions are symmetrical and bilateral. Segmental vitiligo has a more rapid onset, is less common and affects more children than adults. Typically, it is unilateral and has a dermatomal distribution that follows Blaschko’s lines. It may also involve hair follicle depigmentation. The subtypes include focal, mucosal, uni-, bi- and pluri-segmental.

Prognosis 

Vitiligo has an unpredictable clinical course and is usually a chronic and progressive disease. The prognosis is dependent on the patient’s age, disease subtype, distribution, activity and extent. Spontaneous re-pigmentation is rare. With treatment the majority of patients experience more than 75% re-pigmentation but certain areas are less responsive to treatment including distal extremities and lips and there is a possibility of recurrence of disease despite treatment.

Risk factors:

• Age <30 years old 
• Family history of vitiligo 
• Personal or family history of other autoimmune disease: Thyroid disease, Addison’s disease, pernicious anaemia, diabetes mellitus, systemic lupus erythematosus and discoid lupus, alopecia areata, rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren’s syndrome

Diagnosis 

Vitiligo is a clinical diagnosis presenting as lesions of depigmented skin (or hair). It is asymptomatic however at disease onset itchiness can be a symptom.  

These are the following characteristics of the lesions:

• Colour– macules and patches that are hypopigmented then progress to become chalky white and depigmented. Pink patches are noted in more vascular areas. The term trichrome vitiligo can also be used if there is a white centre with a surrounding pale area. 
• Margins– well-demarcated lesions 
• Palpation– Non-scaly and flat lesions 

Extent and distribution– Lesions can be localised or generalised. They are usually bilateral and symmetrical. Sites most commonly affected are distal extremities, axillae, groin, genitalia, face and periorificial skin. It can also affect hair and the epithelium of retina and choroid. The lesions can also be seen at sites of mechanical trauma (like abrasions or burns) which is known as the Koebner phenomenon.

Image Source: Wikimedia Commons (2015). Vitiligo, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Vitiligo2.JPG (Accessed 20 May 2025).

Image Source: Wikimedia Commons (2006). Eyelid Vitilito, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/w/index.php?search=Eyelid_vitiligo_06.jpg&title=Special:MediaSearch&type=image (Accessed 20 May 2025).

Investigation  

Wood’s lamp can be used as it accentuates the contrast between affected and unaffected skin. It is a distinctive blue fluorescence seen in vitiligo but not in simply hypopigmented skin. 

Laboratory investigations include blood tests for thyroid disease, diabetes, pernicious anaemia and Addison’s disease. Autoimmune disorders are associated with Vitiligo and autoimmune thyroiditis is the most commonly associated.

Management

• General measures 
  • Although vitiligo is not life threatening, those with the condition have a reduced quality of life and low self-esteem. 
  • The treatment goal is to improve the appearance of affected skin. 
  • Sun protection such as high factor sunscreen offers both UV-A and UV-B protection all over the body. 
  • Also as reduced sun exposure is being recommended vitamin D levels should be tested and supplementary vitamin D prescribed if necessary. 
  • Minimise skin trauma to prevent new white patches appearing in these sites
  • Camouflage creams and powders especially for dark skinned individuals where the disease appears more obvious.
  • Alternatively, over the counter tanning products and cosmetic micropigmentation and tattoo are options.  
  • Dermatologist referral for management is appropriate when: condition rapidly progressing, uncertain diagnosis, segmental vitiligo, face affected, child affected, pregnant woman, large areas of body affected, person distressed about condition and initial treatment has been unsuccessful.
• Topical therapy
  • Topical corticosteroid and calcineurin inhibitors are first-line treatments in limited (less than 10% body area) or segmental vitiligo.
  • Topical corticosteroids are anti-inflammatory and work by suppressing the immune response against melanocytes and have the most effective response on darker skin, new lesions and sun exposed sites. 
  • The treatment is however not suitable for the face or pregnant woman.
  • Topical corticosteroids commonly used in vitiligo are mometasone or betamethasone valerate 0.1% for a month. 
  • Extended treatment with topical corticosteroid can cause corticosteroid induced atrophy and hypertrichosis. 
  • Hence patients should be monitored for adverse effects such as skin thinning, purpura and striae distensae and treatment response monitored. 
  • Topical calcineurin inhibitors such as tacrolimus and pimecrolimus cream are preferred in children and when lesions are spreading on thin skin or if they are on the face and neck. In comparison to corticosteroid treatment they have better short-term safety profiles including reduced risk of skin thinning. 
• Oral corticosteroid 
  • Can be useful if vitiligo is progressing fast but side effects outweigh benefit so it is not a preferred treatment
• Phototherapy
  • This is an option in widespread vitiligo (more than 10% body surface area), progressive disease or limited vitiligo that has significant psychological impact. 
  • It is also the second line for those where topical therapy has been unsuccessful. 
  • Narrow-band- UVB is safe and effective in adults and children. 
  • To achieve the most optimum response it should be used 2-3 times weekly for 12 months if possible. 
  • Improved efficacy is also seen when combined with topical therapies. 
  • It is more effective in darker skin types. 

• Surgery

  • Surgery is third line treatment and used in stable segmental or stable non-segmental localised vitiligo when medical therapy has not been successful. 
  • The surgical treatment is reserved for cosmetically sensitive sites with no lew lesion, no history of Koebner phenomenon and no change in the lesion in the last 12 months. 
  • It uses surgical grafting where healthy melanocytes are transferred to the depigmented lesion by several techniques. 
  • The several techniques include punch grafting, epidermal blister grafting or ultrathin epidermal sheet grafting. 
  • Successful surgical outcome is more common in younger patients and those with stable segmental vitiligo. 
  • The adverse effects of surgery are scarring or mottled pigmentation on the recipient area. The Koebner phenomenon may also occur at the donor site.
• Depigmentation therapy 
  • Fourth line and used in adults with extensive generalised vitiligo (more than 50% body surface area affected or refractory). 
  • It is a suitable option in dark skinned patients where facial or hand vitiligo is more visible. 
  • Chemicals such as monobenzone 20% or laser therapy are used for depigmentation therapy so that all skin is the same colour. 
  • It can take up to four months to work.

Pityriasis Versicolor 

Pityriasis versicolour (PV) also known as tinea versicolor, is a common superficial fungal infection of the skin. Patients with this condition present with scaly macules that are hypo- or hyperpigmented.

Cause 

It is caused by the lipid dependent Malassezia yeasts and therefore found in areas abundant in sebaceous glands- such as scalp, flexures and upper trunk. This fungus is part of the normal skin flora in over 90% of adults. However, in this condition the Malassezia transforms from yeast cells to a pathogenic mycelial form.  

Factors leading to this pathological form include high temperature, hyperhidrosis, malnutrition, immunodeficiency, immunosuppression and application of occlusive creams or clothing to skin.

Prevalence

PV occurs worldwide but is most common in tropical climates, where prevalence can be as high as 50%. It usually affects adolescents and young adults as sebaceous glands are more active from hormonal changes.

Diagnosis 

The diagnosis is usually made clinically through its characteristic features. There is normally several oval to round macules and confluent patches seen. In lighter skin tone, lesions fail to tan in the summer making it more apparent and in darker skin tone the affected skin is paler. The evoked scale sign is pathognomonic for PV and describes the fine scale on the affected skin becoming more obvious when the skin Is stretched or scraped.  

From the history the skin lesions are asymptomatic, but mild pruritus occurs in some cases. The presenting complaint is usually the cosmetic disfigurement from pigmentary changes associated with the condition. Also, patients will describe a relapsing/recurring history with active flares during increase in weather temperatures.

Image Source: Wikimedia Commons (2011). Pityriasis Versicolor Frontal Originale, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/w/index.php?search=Pityriasis_versicolor_frontal_originale.jpg&title=Special:MediaSearch&type=image (Accessed 20 May 2025).

Investigations 

Microscopic confirmation using potassium hydroxide on skin scrapings can be used to diagnose PV in uncertain instances. The slides should resemble ‘spaghetti and meatballs’ as many short hyphae and spores will be revealed. 

The skin can be examined under a Wood light in a dark room as lesions of PV may fluoresce a characteristic bright yellow or gold colour. The advantage of the test is limited as it is only positive in a third of cases. Only M furfur is fluorescent under Wood light and most infections are from non-fluorescent species of Malassezia. 

A skin biopsy may be done to exclude conditions with similar presentation such as pityriasis alba, seborrheic dermatitis, confluent and reticulated papillomatosis, and vitiligo.

Image Source: Wikimedia Commons (2013). Tinea Versicolor (Wood’s Lamp), Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Tinea_Versicolor_(Wood%27s_Lamp).JPG (Accessed 20 May 2025).

Medical Management 

The preferred first line treatment for PV is topical therapy. The first line treatments for extensive areas include ketoconazole 2% shampoo for 5 days or selenium sulphide for 7 days. These are applied to the affected area for around 10 minutes before being washed off in the shower. The first line treatment for a small area is imidazole cream applied for 3 weeks. These agents are normally well tolerated with the most common adverse effects being skin irritation and contact allergy. Systemic treatment can be used if extensive skin disease or topical treatment has not been effective. This includes oral itraconazole for 7 days or oral fluconazole for 2-4 weeks.  

Spontaneous remission of PV is uncommon, and the infection will persist for many years if not treated. With treatment the prognosis is very good however recurrence is common especially in hot climates. Also, it usually takes 2-3 months for skin pigmentation to fully clear after beginning antifungal treatment, but can persist longer in some cases.

Prevention 

Episodes of PV can recur in humid and warm environments so prophylactic treatment is recommended before exposure such as travel abroad. For this ketoconazole shampoo can be used 3 days before exposure. Oral agents are reserved in patients with extensive disease recurrence that is refractory to topical treatment. For this oral itraconazole can be used.

Post-inflammatory Hypopigmentation 

Post-inflammatory hypopigmentation manifests as irregularly defined pale patches on the skin after inflammation has occurred. Dark skin individuals are especially prone to developing this.  Typically, the surface of the skin is normal, but scaling can be seen if the underlying cause is scaly (such as eczema or psoriasis).

Causes 

Common causes include thermal burns, psoriasis, discoid eczema, lichen planus, cutaneous lupus, laser therapy and cutaneous lupus.

Investigation 

Usually post-inflammatory hypopigmentation is diagnosed clinically by examining the lesion. Skin scraping for mycology or biopsy for histopathology may be needed to diagnose when there is uncertainty. Post-inflammatory hypopigmentation can also be diagnosed via non-invasive methods such as laser scanning microscopy.

Treatment 

Most cases improve spontaneously when the underlying condition has been treated; however this can take months. Also affected areas can be treated with sun exposure unless scarring has occurred. Another option is using prescription camouflage cream that lasts longer and is more effective than normal make-up from drugstores.

Albinism

This is a congenital loss of pigment caused by defective melanin production. Albinism is typically inherited in an autosomal recessive pattern however some forms are X-linked.  

Oculocutaneous albinism (OCA) affects skin, hair, and eyes whilst ocular albinism (OA) which is less common only affects the eyes. 

Levels of pigmentation depend on the type of albinism and how much melanin their body produces. Usually, individuals with albinism have very light skin and hair which can appear white.

Presentation 

The appearance differs between types of albinism and there is a lack of genotype-phenotype correlation especially in severity of albinism. 

The features include varying degrees of skin hypopigmentation. The hair colour can range from white to yellow, red, grey, or brown. The skin can also be more photosensitive. It is worth noting that albinism can be less obvious in fair-skinned individuals as pale features are common.

Melanin is involved in the development of the retina so reduced melanin production can cause visual problems. They can have reduced visual acuity from foveal hypoplasia and misrouting of optic nerves. They can also have astigmatism, photophobia, ametropia, nystagmus, colour vision impairment, and strabismus. Hypopigmentation of the iris leading to iris transillumination is possible.

Image Source: Wikimedia Commons (2007). Albinistic Man Portrait, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/w/index.php?search=Albinisitic_man_portrait.jpg&title=Special:MediaSearch&type=image (Accessed 20 May 2025).

Diagnosis

Diagnosis is based on hypopigmentation of skin, hair, and eyes. Therefore, a baby will be examined on appearance when they’re born to check for signs of missing pigment. 

Individuals with potential albinism will also be referred to an ophthalmologist to check for eye problems. They may use electrodiagnostic testing which is when electrodes are stuck on the scalp to check the connection for the eyes to the part of the brain that controls vision. 

Genetic testing is required to determine the specific subtype of albinism as they overlap clinically.

Treatment 

Treatment is aimed at improving vision from eye problems present in albinism. There is no cure as the failed visual neural development cannot be fixed. 

Individuals with albinism will need regular eye assessments. They will need lenses for low visual acuity, dark glasses for photophobia, surgery for nystagmus and patches for amblyopia. They will also need visual aids such as large computer screens, large print textbooks and magnifying lenses. 

Individuals are also more susceptible to sunburn and hence more likely to develop skin cancers. Therefore, avoiding sunlight, wearing high-factor protection sun cream and examining for skin changes is crucial.

Phenylketonuria 

This is an inherited error in amino acid metabolism caused by deficiency in phenylalanine hydroxylase enzyme activity. The enzyme is responsible for converting dietary phenylalanine to tyrosine. The products of this metabolic pathway are key in the creation of catecholamines, neurotransmitters and melanin. In phenylketonuria due to decreased phenylalanine hydroxylase activity there is elevated blood phenylalanine. The phenotypes range from mild increases in blood phenylalanine concentrations to severe hyperphenylalaninemia.

Classification

PKU can be divided into two main types:

• Classical PKU: higher elevation of blood phenylalanine, usually >1211 micromol/L, accumulation of phenyl ketones and a profound deficiency of phenylalanine hydroxylase activity  
• Non-PKU hyper-phenylalaninaemia: Lower elevation of blood phenylalanine without the accumulation of phenyl ketones

Presentation

Most patients with PKU appear normal at birth and are identified through neonatal screening.  

If this condition is left untreated it can lead to epilepsy, eczema, Parkinson-like features, musty body odour, defects in executive functioning and decreased skin/hair pigmentation. They will also have varying levels of intellectual impairment and behavioural problems.

Diagnosis

Diagnosis is done through UK newborn screening which suggests PKU if there is elevated phenylalanine concentration (>120 mmol/L)

Blood and urinary pterin evaluation or tetrahydrobiopterin (BH4) loading test can also be performed to differentiate between classic PKU from BH4- sensitive PKU and other forms of hyperphenylalaninemia. 

An MRI scan may reveal demyelination in older children who were non-compliant to dietary manipulation.

Treatment 

Patients with PKU should be carefully managed by a specialist metabolic/ paediatric team to avoid consequences of untreated disorders and nutritional deficiencies. 

Mainstay of treatment is dietary changes for life involving restricting dietary protein and phenylalanine intake. The type of diet is dependent on severity and classification of PKU. In classical PKU meat, dairy, rice, pasta and commercial baked goods are restricted. 

These diets are monitored through food diaries, growth measurements and regular assay of phenylalanine levels to ensure patients are receiving adequate calories, protein, and trace minerals. 

In some patients sapropterin (tetrahydrobiopterin) therapy can be used as blood phenylalanine is reduced and protein tolerance is increased.

Tuberous Sclerosis 

Tuberous Sclerosis is a genetic multi-system disorder. It is characterised by the formation of hamartomas (benign tumours) in the brain, skin, kidney, lung, and heart. It is typically caused by the autosomal dominant inheritance of pathogenic variants in tuberous sclerosis 1 or 2 genes.

Presentation

• Differs in severity between patients
• It usually presents in childhood (before the age of 5) with skin change and epilepsy
• Disease can remain latent until adulthood
• Skin changes: 
  • Ash leaf macules on trunk (depigmentation during infancy and can be present from birth)
  • Confetti lesions which are a cluster of hypomelanotic lesions all over the skin
  • Facial angiofibromas which are red nodules over cheeks and nose
  • Shagreen patch over the back and sacrum which are thickened skin areas
  • Poliosis which is a localised patch off white hair
  • Forehead plaques which are raised, red, and pigmented lesions
  • Ungual fibromas found underneath the nails as firm fresh-coloured growth 
  • Skin tags in the axillae, groin and around head can be found

Other clinical features include:

• Cardiac rhabdomyomas in infancy 
• Brain lesions including cortical tubers, subependymal nodules and subependymal giant cell astrocytoma
• Seizure disorders and infantile spasms
• Cardiac arrhythmias 
• Cognitive and behavioural issues 
• Renal angiomyolipoma
• Pulmonary Lymphangioleiomyomatosis

Image Source: Wikimedia Commons (2010). Patient with facial Angiofibromas caused by Tuberous Sclerosis, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Patient_with_facial_angiofibromas_caused_by_tuberous_sclerosis.jpg (Accessed 20 May 2025).

Investigation 

Investigation will depend on presenting features but include:

• Fundoscopy to check for retinal lesions.
• Wood’s lamp to check for hypopigmented patches. 
• MRI of the brain to look for cortical tubers, subependymal nodules and subependymal giant cell astrocytoma. 
• Electroencephalography when there is epilepsy 
• MRI for renal lesions with annual evaluation of renal function 
• ECG for cardiac arrhythmias 
• Echocardiography for cardiac rhabdomyoma 
• Spirometry, CXR and high- resolution CT for pulmonary lymphangioleiomyomatosis

Treatment 

As tuberous sclerosis is a multisystem disorder a multidisciplinary approach with a team of specialist doctors is needed. The extra-dermal manifestations can be managed with medications or surgery. For skin lesions such as angiofibromas, laser treatment or electrosurgery can be used. Surgical excision is also an option for disfiguring skin lesions

Hypopituitarism 

Hypopituitarism is the partial or complete failure of the pituitary gland leading to insufficient hormones being produced. It can be caused by pituitary tumours and cyst, non pituitary tumours compressing pituitary, traumatic brain injury, pituitary surgery, radiation therapy to the sella, postpartum haemorrhage (Sheehan syndrome), subarachnoid haemorrhage and hypophysitis.

Presentation

Clinical presentation varies depending on which specific hormone is deficient. The hypopigmented skin lesions are due to ACTH and a-MSH deficiency. This presents as diffuse pallor in the genital area, breast, and face. ACTH deficiency can also lead to adrenal insufficiency and Addison’s disease.  ACTH deficiency can present acutely as weakness, dizziness, nausea, vomiting, circulatory collapse, fever, and shock. It can present chronically as fatigue, pallor, anorexia, and weight loss. In children they may fail to thrive and have delayed puberty. Other symptoms include hypoglycaemia, hypotension, anaemia, lymphocytosis, eosinophilia, and hyponatremia. Signs and symptoms can also be present from thyroid stimulating hormone deficiency, gonadotrophin deficiency, growth hormone deficiency, and antidiuretic hormone deficiency.

Investigation

Investigations include the endocrine assessment which is the measurement of basal anterior pituitary hormones are their respective target gland hormone levels. These will include ACTH, cortisol, thyroid stimulating hormone, free thyroxine, free triiodothyronine, follicle stimulating hormone, luteinising hormone, oestradiol, testosterone, and prolactin. Insulin-like growth factor 1 is measured for growth hormone secretion as direct growth hormone secretion is pulsatile. 

Serum electrolytes and serum and urine osmolality as ACTH and thyroid stimulating hormone deficiencies can cause hyponatremia. Hypernatremia is seen in diabetes insipidus. 

Water deprivation test is recommended in patients with symptoms of diabetes insipidus. 

MRI imaging of pituitary fossa or CT pituitary scan can be used to identify pathologies in the brain causing the hypopituitarism.

Treatment 

• The mainstay of treatment is replacement of the hormone deficiencies and treatment of the underlying cause or complication of hypopituitarism
• Surgical removal if a tumour is causing hypopituitarism 
• Glucocorticoid hormone replacement therapy for ACTH deficiency.
• For thyroid hormone deficiency, levothyroxine is given after glucocorticoid hormone replacement therapy if there is also ACTH deficiency. 
• Gonadal hormone replacement therapy (oestrogen and progestin) for premenopausal women with central hypogonadism. 
• Testosterone for men with central hypogonadism 
• Growth hormone replacement for growth hormone deficiency 
• Desmopressin for antidiuretic hormone deficiency

Leprosy   

Leprosy is a chronic infectious disease caused by Mycobacterium leprae that affects the skin and peripheral nerves. It is one of the most common causes of peripheral neuropathy worldwide but is rare in the UK.

Diagnosis 

Symptoms can develop insidiously, and three features are required to make the leprosy diagnosis. This includes thickened peripheral nerves, presence of acid-fast bacilli in skin smears/ biopsies and hypopigmented or erythematous skin lesions with loss of sensation.

The initial skin lesion may resolve spontaneously, and this is referred to as indeterminate leprosy.

Lepromatous leprosy is a severe form with high bacterial load where there is systemic involvement including respiratory tract, testes, kidneys, bones, eye, and lymph glands.

Image Source: Wikimedia Commons (2019). Multibacillary Leprosy Lesion, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/w/index.php?search=Multibacillary_leprosy_lesion.jpg&title=Special:MediaSearch&type=image (Accessed 20 May 2025).

Investigation

Skin smear can be done which will be positive for acid-fast bacilli.

Skin and nerve biopsies can also be done to determine classification of the disease and presence of acid-fast bacilli. 

Polymerase chain reaction to detect Mycobacterium leprae DNA in tissue.

Management

Multidrug therapy is needed for leprosy and the medications include rifampicin, dapsone and clofazimine. For the treatment of leprosy reactions corticosteroids are used.