Wednesday, 25 February 2015

Waardenburg syndrome

Piebaldism (Latin and Middle English magpie and Middle English bald, early meaning of white) is a rare, usually autosomal-dominant syndrome with variable phenotype, presenting at birth. Patches of skin totally devoid of pigment are present at birth and usually remain unchanged throughout life. A white forelock can be the only manifestation of the disease. The depigmented lesions may repigment spontaneously, or especially after injury. Regression of the white forelock has also been reported. Photoprotective preparations should be prescribed to protect the amelanotic areas from burning with sun exposure. Other measures include e.g. cosmetic camouflage and grafts of autologous cultured melanocytes.

Waardenburg syndrome (WS) was first described by a Dutch ophthalmologist in 1951. Patients with WS often have characteristic brilliant blue irides as shown in this patient or different coloured irides, such as one blue iris and one brown iris. Sometimes one iris has segments of two different colours. It is one of the syndromes in which extracutaneous manifestations accompany the piebaldism. The symptom most likely to be of practical importance is deafness. Typically piebaldism is not associated with deafness, although piebaldism associated deafness is referred to as Woolf syndrome

There are four classical clinical variants of WS as shown in the table but recent molecular genetics findings have demonstrated at least nine distinct genetic subtypes of WS syndrome, several of which correspond to distinct clinical subtypes not included in these four classical subtypes. WS affects an estimated 1 in 40,000 people. It accounts for 2 to 5 percent of all cases of congenital hearing loss. Types I and II are the most common forms of WS.

WS is usually inherited in an autosomal dominant pattern but sometimes has an autosomal recessive pattern of inheritance as in this patient - figure 1 (her cousin is affected too but with congenital deafness in addition - figure 2).

Although most patients with WS have normal hearing, moderate to profound hearing loss can occur in one or both ears. Hearing loss occurs more often in people with type II than in those with type I but this higher incidence may be due to the difficulty of diagnosing WS2 in patients without hearing loss. Sensorineural deafness results from failure of melanoblasts to migrate to or survive in the stria vascularis in the lateral wall of the cochlea. As shown in the table, mutations in the SOX10EDN3, or EDNRB genes cause type IV Waardenburg syndrome. In addition to melanocyte development, these genes are important for the development of nerve cells in the large intestine. Mutations in any of these genes result in hearing loss, changes in pigmentation, and intestinal problems related to Hirschsprung disease. In Tietz syndrome there are sensorineural deafness, eyebrow hypoplasia, generalized hypopigmentation rather than the localized pigment loss of WS.

All WS forms show marked variability, even within families, and at present it is not possible to predict the severity, even when a mutation is detected. Variable expression and penetrance explain milder or incomplete phenotypes.

Cochlear implantation should be considered a rehabilitative option for WS children with profound deafness, enabling the development and improvement of speech perception and production abilities. 

Figure 1
Note the blue irides and piebaldism (left hand). Poliosis (white forelock) is not shown in the photo (but the patient has it). Poliosis itself is defined as congenital (as in this syndrome) or acquired presence of a localized patch of white hair resulting from the absence or deficiency of melanin in a group of neighbouring follicles. The white forelock can be absent. Premature greying may develop with or without the white forelock.

Figure 2

MITF = microphthalmia associated transcription factor. MITF controls the expression of various genes that are essential for normal melanin synthesis in melanocytes.

This page was last updated in March 2015

Wednesday, 18 February 2015


Blaschkitis is a unilateral remitting and relapsing eruption of itchy inflammatory vesicles and papules (resembling eczema) that occurs usually on the trunk in adults  following Blaschko’s linesIt would be difficult to distinguish from linear Grover’s disease. Blaschko's lines pattern is attributed to the lines of migration and proliferation of epidermal cells during embryogenesis. The lines do not correspond to any known nervous, vascular or lymphatic structures.

The histopathology is more eczematous (spongiotic) than lichenoid. Some have considered it to represent an adult version of lichen striatus and actually, the acronym BLAISE (Blaschko linear acquired inflammatory skin eruption) has been used to cover both. Blaschkitis (adults) is rarer, more itchy, more papulovesicular, more extensive, resolving more rapidly, and relapsing more frequently than lichen striatus (children). BLAISE is best regarded as a description rather than a diagnosis, pending identification that is more precise. Steroids may be effective.

This page was last updated in February 2015

Wednesday, 11 February 2015

FRCP Glasg UK in good standing

The Royal College of Physicians of Glasgow, UK (a charity) promotes the best levels of health and high standards of healthcare for people throughout the world. It was established in 1599After reaching the consultant status, advancement from Membership to Fellowship of the Royal College of Physicians (FRCP Status) might be achieved. Successful candidates must fulfil specific criteria employed by the Royal College Council.

I have been elevated from Member Status to Fellow Status, FRCP Glasgow UK (Fellow of the Royal College of Physicians of Glasgow UK), in the Royal College's words, "having acquired distinction as a Physician and having completed training appropriate to the Regulations". I became a Royal College Clinical Educator on 23/9/2016The fees are for the Royal College only.  

Being a Royal College clinical educatoram fully committed to trainer development at the Royal College of Physicians, Glasgow, UK.

I am very pleased that the Royal College has chosen my words.

Monday, 9 February 2015

Treatment of zoster in HIV-seropositive patients

Herpes zoster may occur at any stage of HIV infection, and may be the first clinical evidence of previously undiagnosed HIV infection. Herpes zoster has also been recognized as a manifestation of immune reconstitution disease.

Varicella zoster virus (VZV) is a human neurotropic alphaherpes DNA virus that is usually transmitted by the respiratory route. It is the causative agent of both varicella (chickenpox) and zoster (shingles). Varicella results from primary infection of VZV and is a common childhood illness, usually presenting as a benign self-limiting illness with fever and generalized pruritic vesicular rash. Following primary infection, VZV establishes lifelong latency in the cells of the dorsal root ganglia. Reactivation results in herpes zoster disease. In HIV-seropositive patients, reactivation is more common, and in those with advanced immune deficiency may result in severe and disseminated clinical disease.

In the general population, the incidence of herpes zoster (shingles) is 1.5–3 per 1000 persons per year. It is seen more frequently in patients aged 60 years and older and in those who are immunocompromised. Individuals with HIV infection have significantly higher rates of herpes zoster than the general population with an estimated relative risk of 15 or greater compared to age-matched HIV-seronegative controls. Herpes zoster occurs more frequently in HIV-seropositive persons with a CD4 count <200–250 cells/μL and, unlike the non-immunocompromised individual, recurrences are common (up to 20–30% of cases) which may be more severe with increasing immune deficiency.

In patients with advanced HIV disease, prolonged lesion formation, and dissemination of virus can occur. Cutaneous dissemination may be widespread, making it indistinguishable from primary varicella infection. Despite an impaired immune system, the majority of HIV-seropositive patients with zoster do not develop life-threatening complications, and most have an uncomplicated clinical course.

Treatment of zoster in HIV-seropositive patients should begin as soon as possible (preferably within 72 h of onset of the rash) and be continued for 2 days after all lesions have dried and crusted. Intravenous foscarnet is the agent of choice for aciclovir-resistant VZV infection.

Lesions evolve over 1–2 days to form vesicles. 

In HIV-seropositive patients, zoster may be particularly haemorrhagic

Treatment should be continued for 2 days after all lesions have dried and crusted.

This page was last updated in February 2015

Main Works of Reference List (The first eight are my top favourites)

  • British National Formulary
  • British National Formulary for Children
  • Guidelines (BAD - BASHH - BHIVA - Uroweb)
  • Oxford Handbook of Genitourinary Medicine, HIV, and Sexual Health
  • Oxford Handbook of Medical Dermatology
  • Rook's Textbook of Dermatology
  • Simple Skin Surgery
  • Weedon's Skin Pathology
  • A Concise Atlas of Dermatopathology (P Mckee)
  • Andrews' Diseases of the Skin
  • Andrology (Nieschlag E FRCP, Behre M and Nieschlag S)
  • Bailey and Love's Short Practice of Surgery
  • Davidson's Essentials of Medicine
  • Davidson's Principles and Practice of Medicine
  • Fitzpatrick's Colour Atlas and Synopsis of Clinical Dermatology (Klaus Wolff FRCP and Richard Allen Johnson)
  • Fitzpatrick’s Dermatology in General Medicine
  • Ganong's Review of Medical Physiology
  • Gray's Anatomy
  • Hamilton Bailey's Demonstrations of Physical Signs in Clinical Surgery
  • Hutchison's Clinical Methods
  • Lever's Histopathology of the Skin
  • Lever's Histopathology of the Skin (Atlas and Synopsis)
  • Macleod's Clinical Examination
  • Martindale: The Complete Drug Reference
  • Oxford Handbook of Clinical Examination and Practical Skills
  • Oxford Textbook of Medicine
  • Practical Dermatopathology (R Rapini)
  • Sexually Transmitted Diseases (Holmes K et al)
  • Statistics in Clinical Practice (D Coggon FRCP)
  • Stockley's Drug Interactions
  • Treatment of Skin Disease: Comprehensive Therapeutic Strategies
  • Yen & Jaffe's Reproductive Endocrinology