Friday, 10 December 2010

Perforating granuloma annulare

Different clinical variants of granuloma annulare have been described. The most common form, as its name indicates, is an annular lesion. The annular margin is firm to palpation and may be continuous or consist of discrete or coalescent papules in a complete or partial circle. The epidermis is usually normal, but surface markings may be attenuated over individual papules whose colour may be skin coloured, erythematous, or violaceous. The lesions are usually asymptomatic. Reports of an association with diabetes mellitus are controversial. Several other associations have been reported.


There is overlap between the different variants, and more than one morphologic type may co-exist in the same patient. It must be noted that some lesions enlarge as nodules rather than having an annular morphology. A diagnosis of localized annular granuloma annulare is made on clinical examination. Histopathologic examination is necessary when the presentation is atypical. The clinical diagnosis is definitely difficult when annular lesions are absent.


Perforating granuloma annulare was named by Owens and Freeman in 1971. It exhibits transepidermal elimination of degenerating collagen histopathologically, the so called “necrobiotic collagen” hence classified as a secondary perforating disorder. As the late A Bernard Ackerman used to stress, collagen is a fibre that can undergo degeneration but cannot become necrotic; only cells can undergo necrosis. Perforating granuloma annulare starts clinically as small papules with central umbilications. Lesions may be localized (usually in an acral distribution) or generalized. Perforating granuloma annulare lesions have been present in some of the reported HIV-positive patients with granuloma annulare.


In perforating granuloma annulare there is a superficial area of the so called necrobiosis (better called degenerated collagen, as stated above) and mucin accumulation surrounded by palisading histiocytes, situated beneath a perforation in the epidermis. The so called “necrobiotic material” and mucin are extruded via the perforation. At the margins of the perforation there are varying degrees of epidermal hyperplasia. It should be noted that the epidermal changes are inconspicuous in other variants of granuloma annulare.


Mucinous degeneration of collagen appears bluish or at least shows decrease in the degree of eosinophilic (pink) staining. Mucin can be seen more readily by staining with Alcian blue or colloidal iron.


The differential diagnosis of perforating granuloma annulare includes some dermatoses such as insect bites, molluscum contagiosum, pityriasis lichenoides et varioliformis acuta, transepidermal elimination disorders such as perforating collagenosis and acquired perforating dermatosis, sarcoidosis and papulonecrotic tuberculide. Epithelioid sarcoma may masquerade as perforating granuloma annulare. It should be noted that epithelioid sarcoma that can simulate perforating granuloma annulare, as stated, may also contain mucin. Clues to epithelioid sarcoma include ulceration, cytologic atypia, necrotic foci that include necrotic epithelioid cells and possibly a history of recurrence. Immunohistochemically, epithelioid sarcoma can be distinguished from granuloma annulare by positivity for epithelial membrane antigen and (Cyto)keratin.


The tendency of granuloma annulare to remit spontaneously (but it should be noted that perforating granuloma annulare may leave a hypo- or hyperpigmented scar) complicates accurate assessment of the efficacy of any treatment (such as intralesional triamcinolone 2.5 - 3 mg/mL).

Monday, 6 December 2010

Lymphocytoma cutis

Lymphocytoma cutis is a benign lymphocyte hyperplasia (B-cell reaction to an antigen such as a red tattoo, Borrelia burgdorferi, injected drug, vaccine) that prefers the head and neck region,and can be associated with sunlight sensitivity. It presents as red or violaceous nodules or plaques and is commoner in females.


It can remain stable or regress over time. Lymphocytoma cutis can be complicated by the development of primary cutaneous B cell lymphoma. Whether the initial diagnosis in such circumstances should have been primary B-cell lymphoma and was missed, or not is uncertain. Lymphocytoma cutis has been classified as a “pseudolymphoma” but it should be noted that the late A Bernard Ackerman used to stress that there is no need to use the term "pseudolymphoma" whenever specific diagnosis can be made.


The lymphocyte infiltrate affects the reticular dermis rather than the subcutaneous fat (In primary B-cell lymphoma the subcutaneous fat may be infiltrated); it spares the papillary dermis forming a grenz zone. It can be wedge shaped, apex of which is directed at the subcutaneous fat but it does not involve it. However, in
reactions at the site of vaccination, the subcutis is predominantly
affected with little dermal involvement. The infiltrate is considered to be bottom heavy if compared to epidermotropism of mycosis fungoides where there is no grenz zone. Some have sub-typed the lymphocytoma cutis into B-cell or T-cell, according to which lymphoid cell pattern is present on the biopsy. Further divisions within these groups are largely by its cause, if any is identified but many won't follow this classification as it will include distinct conditions under the umbrella term of pseudolymphoma which should be avoided whenever a specific diagnosis can be made. Appendages and blood vessels are spared. The infiltrate is polymorphous (lymphocytes, starry sky macrophages (with tingible/stained bodies), eosinophils and plasma cells). The infiltrate shows a mixture of kappa and lambda light chain positive B cells (polyclonal) by immunohistochemical analysis. Normally, B cells undergo gene rearrangement of one of their immunoglobulin heavy chain genes at an early stage in B-cell development. In lymphocytoma cutis, immunoglobulin heavy chain gene rearrangement polymerase chain reaction or southern blot analysis shows polyclonal rearrangement. CD1a+ dendritic cells (originally observed in the infiltrates of cutaneous T-cell lymphoma) are usually abundant by immunohistochemical analysis. It can contain lymphoid follicles (with germinal centres)[in classic cases] resembling the appearance of lymph node. Differentiation from primary B-cell lymphoma (particularly marginal zone lymphoma “MZL”) can be difficult clinically and histopathologically (presence of atypical lymphoid cells would suggest a primary cutaneous MZL).


A spectrum of B-cell neoplasia ranging from polyclonal lymphocytoma cutis (benign) via oligoclonal and monoclonal lymphocytoma cutis into primary cutaneous B-cell lymphoma (malignant) is possible.


Jessner’s benign lymphocytic infiltration (T-cell infiltrate,  predominantly in the lower dermis and concentrated tightly around blood vessels and within the lymphocytic infiltrate there is no evidence of follicle formation), tumid discoid lupus erythematosus (basal cell liquefaction degeneration with positive direct immunofluorescence), polymorphic light eruption and insect bites reactions are also among the differential diagnoses.


Treatment modalities (no treatment of proven value unless a cause is found and even then elimination of the cause does not necessarily cures the disease, sunscreens are used if there is sunlight sensitivity) include: intralesional steroid injection, topical steroids, oral hydroxycloroquine, intralesional interferon-alpha-2A, and topical tacrolimus. Observation with careful follow-up is a reasonable option.

This page was last updated in September 2014

Saturday, 4 December 2010

Linear porokeratosis

Linear porokeratosis has been classified as an epidermal naevus but it is still clinically and histopathologically indistinguishable from the lesions of generalized porokeratosis (disorder of keratinization). Linear porokeratosis probably reflects mosaicism for a gene responsible for generalized porokeratosis (autosomal dominant, but CAP syndrome “craniosynostosis – anal anomalies – porokeratosis” appears to segregate as autosomal recessive trait). This mosaicism can be explained by loss of heterozygosity for this dominant gene. Accordingly, an individual with inherited generalized porokeratosis undergoes a somatic mutation affecting the normal allele resulting in clonal loss of heterozygosity. The resultant line has ‘double the dose’ of porokeratosis. Skin cancers in porokeratosis are particularly associated with the linear variant. Overexpression of p53 [tumour suppressor protein (coded for by 17p)] has been reported in linear porokeratosis and in a superimposed squamous cell carcinoma. Many of topical agents, such as imiquimod 5% cream, an immune response modifier that induces cytokines such as interferon-alfa, used in the treatment cause initial inflammation which is followed by resolution.


Linear porokeratosis, with its ‘double the dose’ of porokeratosis, contrasts with the background skin, with its ‘one dose’ porokeratosis. Thus patients with linear porokeratosis can later develop disseminated superficial actinic porokeratosis (DSAP), the commonest presentation of porokeratoses, and children or siblings of patients with DSAP can have linear porokeratosis. Having said so, linear porokeratosis usually occurs sporadically and even many patients with generalised porokeratosis itself have no family history. Linear porokeratosis can exacerbate during episodes of liver failure, and improve following transplantation (unlike generalized porokeratosis that can be provoked by immune suppression).


Almost all epidermal naevi follow the pattern of lines documented by Blaschko from drawings of epidermal naevi. The 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 bands of abnormal skin represent clones of cells carrying a mutation in a gene expressed in the skin. Mosaicism impact on the phenotype relates to the proportion of cells that harbour the mutation and their distribution. Mosaic describes an art form in which pictures are produced by joining together tiny pieces of different coloured stone or glass. The term is used in genetics to describe individuals composed of cells of different genotypes, such as patients with Turner syndrome who have both 45, XO and 46, XX cells. The pattern may vary according to cell type and timing of mosaicism. In the skin, genetic mosaicism classically appears as Blaschko's lines.


It should be noted that the term "porokeratosis" was first used by Vittorio Mibelli, Italian dermatologist, in 1893. Porokeratoses are characterised by presence of abnormal (disordered metabolism/increased cell kinetics) clone of keratinocytes showing varying degrees of dysplasia with gradual centrifugal migration of this clone resulting in a keratotic lesion that can progress to overt cutaneous neoplasm. The term “porokeratosis” is a misnomer, as porokeratosis has nothing to do with pores of sweat glands. Actually the lesions may or may not involve the eccrine sweat duct. The characteristic histopathology is seen in the edge of the lesion. The stratum corneum is hyperkeratotic, and at the raised border a column of poorly staining parakeratotic stratum corneum cells, the cornoid lamella, is seen running through the surrounding normal-staining cells. There is hypogranulosis beneath the cornoid lamella. Cornoid lamellae may also been seen in other conditions such as common warts (distinguished by presence of koilocytes), actinic keratosis (distinguished by presence of cytologic atypia) and some ichthyoses.

Tuesday, 2 November 2010

Continuing Professional Development (CPD) Diary Proposal

The credit requirements for a 5-Year cycle are a total of 250 CPD credits (with the requirement of 50 credits per year). Of the 250 CPD credits, 125 must be external credits (100 clinical external credits and 25 non-clinical external credits). Non-clinical credits concern educational activities that are not directly related to clinical issues.












Internal credits are given for events within the hospital or clinic such as journal clubs, grand rounds, histopathology meetings, local evening medical meetings, audit, managerial work and dealing with ethical and legal issues. 


External credits are given for events outside the hospital or clinic (attending relevant conferences/meetings, workshops, and courses such as international conferences, regional clinical/managerial meetings and clinical/management courses). 25 external credits (20 clinical external credits and 5 non-clinical external credits) are required per yeare-Learning activities are credited with CPD which count toward your external CPD to a maximum of 5 credits per year and any additional CPD gained from e-Learning activities can be recorded as personal CPD.   


Personal credits relate to study such as private reading of journals and texts, carrying out information searches, writing articles, preparing lectures, CPD activities online, reflective notes writing (clarifying your thoughts after a specific experience), refereeing papers, researching, making presentations at conferences or to examining postgraduates, writing examination questions, dealing with ethical and legal issues and managerial work. Only 10 personal credits may count per year.  


Exemption credits may only be granted by the national society PER YEAR in exceptional circumstances when a physician is unable to meet the yearly minimum requirements due to illness, maternity leave or long absence from work. In such circumstances, these exemption credits claimed must be made up in subsequent years by completing extra credits as they are not counted towards the 5-Year cycle.


Normally medical practice involves internal, external and personal educational activities with both clinical and non-clinical nature and there should be a balance in the learning methods. In any one-year period, a minimum of 25 credits MUST be external credits "20 clinical external credits + 5 non-clinical external credits"; the minimum remaining credits (25), should be "internal credits + personal credits" or "internal credits + personal credits + external credits". Only 10 personal credits may count toward the total yearly minimum credit requirement as stated above.

Note that:

1 CPD credit = one hour spent learning (whether at a meeting, or event, or studying, preparing a lecture, reading a paper or otherwise). Please note that speaking per se does not count as a learning activity. 

• If you exceed 250 credits in one 5-Year cycle you cannot carry the extra credits into the next five-year cycle.

• It is important to record each CDP activity at the time when you complete it (ensure that the date is written). Any relevant documentation must be retained for at least 5 years.

• The CPD year runs from 1 January to 31 December. You have until 31 March to email the relevant body your CPD diary for the year ending the previous December. 

• The relevant body audits a random 5% of all members by 30 June every year to ensure that their CPD diaries are accurate.



This page was last updated in February  2017.

Wednesday, 27 October 2010

Klinefelter’s syndrome



Klinefelter’s syndrome was named after Harry Klinefelter, an endocrinologist at Massachusetts General Hospital, USA in 1942 who thought it was an endocrine disorder due to lack of a second testicular hormone that he postulated but was unable to identify. The postulated hormone, inhibin, was isolated later.

There are two inhibins (inhibin A and inhibin B), both of which inhibit FSH release by direct action on the pituitary though inhibin B appears to be the FSH regulating inhibin. Inhibin B is a marker of spermatogenesis and Sertoli cell function and is produced by the Sertoli cells and it is the major negative feedback regulator of FSH release. It is undetectable in patients with Klinefelter’s syndrome hence the elevated FSH.  Inhibin B correlates positively with sperm concentration and testicular volume and it correlates negatively with the degree of testicular damage.

The 47, XXY karyotype characteristic of Klinefelter syndrome was first described in Scotland, UK in 1959. XXY karyotype of maternal origin arises by an error at either meiosis I (MI) [commonest source of maternal nondisjunction - ? advanced maternal age] or meiosis II (MII). XXY karyotype of paternal origin arises by an MI error with the formation of XY sperm (? advanced paternal age) because, error at MII forms XX sperm or YY sperm rather than XY sperm.

Klinefelter’s syndrome is the commonest sex chromosome abnormality.

Klinefelter’s syndrome is a classic example of seminiferous tubular sclerosis (where germ cells and Sertoli cells are not identified lining  many sclerotic seminiferous tubules that reveal hyalinising fibrosis with absent spermatogenesis, seminiferous tubules can be completely obliterated). In isolated cases several tubules may show intact spermatogenesis with elongated spermatids and sperms. 

Germ cell presence and sperm production are variable in men with Klinefelter’s mosaicism. The term mosaic describes an art form in which pictures are produced by joining together tiny pieces of different coloured stone or glass. The term is used in genetics to describe individuals composed of cells of different genotypes, such as  Klinefelter’s mosaicism patients and patients with Turner syndrome who have both 45, XO and 46, XX cells. The pattern may vary according to cell type and timing of mosaicism. Mosaic forms of Klinefelter's syndrome represent mitotic nondisjunction within the developing zygote and are thought to occur in approximately 10% of individuals with this condition. The commonest form observed is 46, XY / 47, XXY mosaicism.


A nonmosaic Klinefelter’s syndrome patient was able to impregnate his wife without assisted reproductive technology then showed severe oligoasthenozoospermia followed by azoospermia*. This and other studies suggest that early (before the age of 35 years) sperm (if detected) retrieval and cryopreservation for future management of infertility in Klinefelter's syndrome should be considered.

The mechanism by which an extra X chromosome renders patients infertile is not known. Usually azoospermia is established. In some patients few sperm or severe oligoasthenoteratospermia can be found. Spontaneous pregnancies are extremely rare.
   


The phenotype is normal (there might be disproportionately long legs, clinodactyly and learning difficulties) before puberty, which starts at the normal age but as a process fails to progress normally.

Adult men with Klinefelter’s syndrome have small firm testicles (testicular volume is rarely over 4 ml). The phenotype can vary from a normally virilised man to one with stigmata of androgen deficiency (Leydig cell function is commonly impaired but Leydig cells are present in normal or increased numbers), including female hair distribution, scanty body hair and long legs (usually tall patients) because of late epiphyseal closure. Patients may develop gynaecomastia (with risk of breast cancer). Ultrasound findings of testicular microlithiasis can be seen in men with Klinefelter’s syndrome. There are some Klinefelter's syndrome variants that were reported e.g. 49 , XXXXY variant with several additional features such as microcephaly, mental retardation, facial dysmorphism, radioulnar synostosis, micropenis, and muscular hypotonia. As the number of X chromosomes increases, the severity of mental retardation and of malformations also increases. Each extra X is associated with a 15- to 16-point reduction in IQ, with language most affected, particularly expressive language skills. Compared with their classmates, patients may notice differences and become socially alienated (social maladjustment). This may explain the fact that some patients become criminals on trying to prove one's manhood!


FSH and LH levels increase to hypergonadotropic levels, inhibin B decreases to undetectable levels, testosterone levels are low or low-normal or low (thus libido can be normal) and oestradiol levels are normal or elevated. The diagnosis is confirmed by chromosome studies.

 

Reported associated features include e.g. osteoporosis, psychiatric disorders, leg ulcers especially in combination with hyperpigmentation or atrophie blanche (androgens may protect against their development), incontinentia pigmenti (as incontinentia pigmenti trait is usually lethal in males, it has been proposed that the second X chromosome protects against foetal death), and systemic lupus erythematosus [SLE](androgens may normalise SLE haematological and serological abnormalities with clinical remission).


Due to the significant increase of sex chromosomal and autosomal abnormalities in the embryos of Klinefelter patients generated through ICSI, pre-implantation genetic diagnosis (PGD) is strongly advised.


Testosterone replacement is needed as the patient ages and it should be noted that a threshold serum testosterone level is required to achieve full efficacy with PDE5i (phosphodiesterase-5 inhibitors) when required. There is controversy over the indication for testosterone treatment of children with Klinefelter's syndrome (? might improve learning ability). As stated before, compared with their classmates, patients may notice differences and become socially alienated (social maladjustment). This may explain the fact that some patients become criminals on trying to prove one's manhood! Thus testosterone replacement should not lead to exceeding the upper normal values.  


Yearly follow up of men with Klinefelter’s syndrome is required and androgen replacement therapy should be started when testosterone level is in the range of hypoandrogenism. All men with Klinefelter’s syndrome who undergo testicular biopsy procedures for sperm retrieval need long-term endocrine follow-up.


*Ichioka K, Utsunomiya N, Kohei N, Ueda N, Inoue K, Terai A. Adult onset of declining spermatogenesis in a man with nonmosaic Klinefelter’s syndrome. Fertil Steril 2006; 85(5): 1511.e1-2.


This page was last updated in April 2013


Tuesday, 26 October 2010

Gonorrhoea

Gonococcal urethritis (Gonorrhoea). Gonorrhoea owes its name to the Greek physician Galen in the second century AD, as it was then thought that the discharge of urethral pus was seminal fluid-hence being misnamed “gonorrhoea” (Greek, flow of seed). Thus from the very earliest times it was characterised as being “a male disease” and little attention was given to its manifestations in females.


As the concept developed that gonorrhoea resulted from coitus (venery), steps were taken for its control and it is said that in the Middle Ages prostitutes of Paris were quartered in domiciles in the Les Clapiers (les clapiers meaning rabbit hutches, the slang name for brothels in Paris during the Middle Ages) district there, hence the term clap, which is still commonly used to refer to this disease.


Extragenital infections include rectal, pharyngeal and conjunctival infections. 

Gonorrhoea has a high infectivity and is easily transmitted before symptoms appear (during the incubation period - the incubation period ranges from 1 to 14 days or even longer in men). In males, the usual presentation is with acute anterior urethritis. There may be slight tender enlargement of the superficial inguinal lymph nodes. Urethritis in men may be divided into gonococcal (gonorrhoea) or non-gonococcal urethritis (NGU); there is considerable overlap and differentiation on clinical grounds alone is not advised. More than 50% of females are asymptomatic (seen as contacts on examination). Symptoms if present (e.g. lower abdominal pain, dysuria, and vaginal discharge) appear within 10 days of infection.

NGU occurring soon after curative therapy for urethral gonorrhoea is called postgonococcal urethritis. NGU can be further classified into Chlamydia trachomatis-positive and Chlamydia trachomatis -negative NGU. There is a proportion of cases of NGU that are not sexually transmitted.

The gonococcus (Neisseria gonorrhoeae)  has a predilection for columnar epithelium which is readily available after the organism has gained entrance to the urethra, rectum, pharynx and conjunctiva in both sexes and endocervix and Bartholin’s ducts in females. The infection can spread to other structures lined with susceptible epithelium such as Littré’s glands, Cowper’s glands, prostate gland, seminal vesicles and epididymes in the male and Skene’s glands and Fallopian tubes in the female. The gonococci, with the help of pili and other surface proteins, attach themselves to the epithelial cells. This attachment protects them from being dislodged by the normal flow of urine or mucous secretions. They may also become embedded within the epithelial cells. However, once phagocytosed by neutrophils (microphages), the gonococci may undergo lysis, especially after appropriate antibiotic treatment.


In contrast to female adults, in prepubertal girls the nonoestrogenized alkaline thin immature vaginal mucosa may be infected and colonised with N. gonorrhoeae. A clinician who is examining a prepubertal female for a gonococcal infection should be aware that contrary to female adults, it is not necessary to obtain a specimen from the cervical canal; a specimen from the vaginal canal suffices.


Gonococcal urethritis in boys, vulvo-vaginitis in girls and pharyngeal and rectal infection in both sexes are almost always the result of sexual abuse.


Complications in males include infection of the median raphe, Tysonitis, meatal paraurethral gland abscess, inflammation of Littré’s glands and periurethral cellulitis and abscess, urethral strictures and fistulae, Cowperitis and abscess formation, prostatitis and seminal vesiculitis and epididymitis.

Complications in females include inflammation of the paraurethral (Skene’s) glands, Bartholinitis with abscess formation, and pelvic inflammatory disease (PID). In pregnancy, genital infection is less likely to be complicated by PID (because of thickening of cervical mucus) but other adverse outcomes include e.g. premature rupture of membranes, and postpartum/intrapartum or postabortal endometritis.

Systemic complications include perihepatitis and disseminated gonococcal infection (DGI) (In DGI factors include e.g. serogroup IA-1 & 2/ auxotype AHU [arginine, hypoxanthine, and uracil] dependent). In DGI, the preceding genital infection tends to be asymptomatic and the patient usually presents with mild fever, gonococcal dermatitis especially at extremities, and arthralgia +/- arthritis.  AHU/IA-1 & 2 strains accumulate in the population because of their ability to cause asymptomatic infection in men. AHU/IA-1 & 2 strains are particularly susceptible to the penicillins but this varies over time and penicillin resistant strains now play a significant role.


Neonatal gonococcal infection occurs because of exposure in birth canal during labour and includes gonococcal ophthalmia neonatorum, gonococcal arthritis, anogenital infection, pharyngeal infection and other infections such as scalp abscess following trauma to scalp e.g. with intrauterine foetal monitoring.

Five or more polymorphonuclear leucocytes per high power field (in at least five x 1000 oil immersion microscopic fields) in the Gram-stained urethral smear will confirm urethritis and the presence of Gram-negative intracellular diplococci (red kidney bean-shaped organisms) within polymorphonuclear leucocytes (microphages) would enable the physician to make a presumptive diagnosis of gonococcal urethritis. Confirmation is by culture of the organism (also allows sensitivity testing) and differentiation from other Neisseria species by antigenic (monoclonal antibody test) or biochemical testing (gonococcus utilises glucose only). The culture medium is examined at 24 and 48 hours for growth. Growth is optimal at 35–37 °C in a 5% CO2 atmosphere, at a pH of about 6.5–7.5. For urethral specimens from symptomatic men, cultures on selective “antibiotic-containing” (e.g. modified Thayer-Martin medium) and nonselective media are equally sensitive, because the concentration of gonococci in the urethra usually exceeds that of other flora. In contrast, selective media are preferred for culturing the endocervix, rectum, and pharynx, where other, less fastidious bacteria often outnumber N. gonorrhoeae. Test of cure by culture should be delayed for at least 72 after treatment.




Nucleic acid amplification tests (NAATs) are extremely sensitive and will detect very small amounts of DNA or rRNA. Detection does not necessarily indicate that the organism is viable [the test of cure should be delayed for at least 2 weeks after treatment to avoid false positive results]. Using NAATs that exhibit little cross-reactivity reduces false positive results. NAATs are more sensitive than culture and can also be used as diagnostic/screening tests on non-invasively collected specimens (urine in men and self-taken vulvovaginal swabs). NAATs allow dual detection of N. gonorrhoeae and Chlamydia trachomatis too. Urine is a suitable sample in NAAT screening for Chlamydia trachomatis and so may be tested additionally for N. gonorrhoeae in both men and women, but NAATs sensitivity to detect N. gonorrhoeae in women is higher if a self-taken vulvovaginal swab is used. Confirmation of NAAT reactivity by culture is necessary (urine is not considered a suitable sample for culturing of N. gonorrhoeae or Chlamydia trachomatis) and allows antimicrobial sensitivity testing and thus resistant strains can be identified. Resistance may be due to plasmids (circular DNA fragments independent of chromosome) or chromosome mutations.


Gonorrhoea is known to facilitate the transmission of HIV (increase in detectable HIV in urethral/cervical secretions when infection is present). The impact of untreatable gonorrhoea (given the lack of new anti-gonococcal drugs on the horizon, gonorrhoea may eventually become untreatable) on HIV transmission could be enormous in countries with a high HIV prevalence*.

Uncomplicated gonorrhoea responds to a single dose of suitable antimicrobial (in view of the global increase in multidrug-resistant gonorrhoea, the wisdom of continued single-dose treatment may be challenged and extended treatment may be required), the choice of dose and drug depending on antimicrobial sensitivity.

Currently, 
dual treatment with ceftriaxone plus azithromycin is generally advised for the treatment of uncomplicated gonorrhoea (irrespective of the results of chlamydia testing) in order to mitigate against the selection of gonococci with reduced susceptibility to cephalosporins. The rationale is that it is difficult for an organism to develop simultaneous resistance to two different antimicrobial classes, meaning that dual treatment creates a pharmacological barrier to the emergence of isolates exhibiting resistance to one component of the recommended therapy. There is no good evidence for any antimicrobial synergy between ceftriaxone and azithromycin and this is NOT the reason for recommending dual therapy.


Management of sexually transmitted urethritis includes, screening for other STIs, contact tracing and sexual partner(s) notification, education/counselling, examination, investigation and treatment

*Lewis DAThe Gonococcus fights back: is this time a knock out? Sex Transm Infect 20108641521.

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)
  • Ackerman's Resolving Quandaries in Dermatology, Pathology and Dermatopathology
  • 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