Review Articles
Genito-urinary disorders and diabetes
GR Scott MB MRCP (UK)Consultant in Genitro-Urinary Medicine and BM Frier BSC MD FRCP,Consultant Physician,
Correspondence to: Dr Brian M Frier, Department of Diabetes, Royal Infirmary of Edinburgh,
Introduction
Diabetes is associated with a wide
variety of infections particularly when
glycaemic control is poor, although it is
debatable whether diabetic patients
have a greater predisposition overall to
infective disease. Several infective and
inflammatory disorders affect the
genito-urinary system in patients with
diabetes and the presentation and treat-
ment of these are reviewed.
Candidiasis
Genital candidiasis is the most frequent
genito-urinary manifestation of diabetes
and isoften a presentingcomplaint at the
time of diagnosis. It is a standard maxim
that the urine of all patients who develop
genital candidiasis should be tested
routinely for glycosuria. Increased tissue
and urinary glucose promote candidal
growth, although immunological factors
may also have a minor role. In women,
candida species frequently colonise the
vagina from the reservoir of infection in
the gut. Growth is favoured by a high glu-
cose concentration and the white, curdy
vaginal exudate which occurs produces a
white discharge and vulva1 itch. On
examination, the labia minora are
erythematous and oedema and fissuring
may occur (Figure I ) . The vaginal
mucosa is inflamed and adherent white
plaques may be noted (Figure21, removal
of which reveals underlying erythema
and may result in bleeding. Alterna-
tively, primary cutaneous candidiasis
may develop, predominantly affecting
the outer parts of the labia and genito-
crural folds, with the appearance of a
scalloped leading edge with satellite
lesions and pustule formation. The clini-
cal diagnosis of candidiasis is confirmed
by detection of fungal pseudohyphae in a
smear of vaginal exudate using a Gram’s
stain; candida species can be isolated by
culture on Sabouraud’s medium.
Specimens far culture from vaginal
swabs should be sent to the laboratory in
a suitable transport medium, such as
Stuart’s or Amies. Definitive micro-
biological diagnosis is to be encouraged
as there is evidence that candidiasis is
over-diagnosed as a cause of vulvo-vagi-
nal irritation in diabetic women’.
In the female patient, treatment with
an imidazole drug such as clotrimazole
or econazole is administered in the form
of a single vaginal pessary and cream, or
fluconazole as a single oral dose of
Practical Diabetes November/December Vol8 No 6
Royal Infirmary, Edinburgh
Edinburgh EH3 9YW
150mg may be prescribed. Recurrence is
common, particularly if glycaemic con-
trol remains sub-optimal. Simultaneous
treatment of the patient’s sexual partner,
although frequently advocated, is sel-
dom of benefit in preventing recurrence.
In the male, infection of the sub-pre-
putial sac results in a chronic balano pos-
thitis (Figure3), giving symptoms of sub-
preputial discharge and itch. If
untreated, phimosis may result. Candi-
dal balanitis is also over-diagnosed and it
is worthwhile confirming the diagnosis
by microscopy or culture. Treatment
with clotrimazole or econazole cream
will provide symptomatic relief until
hyperglycaemia has bccn treated effec-
tively. In patients who have a tight
phimosis where access to the sub-pre-
putial sac may be precluded, the use of
fluconazole in a single oral dose (150mg)
is usually effective.
Genital warts
Genital warts are caused by infection
with human papilloma virus (HPV)
types six, 11,16 and 18and, occasionally,
types 31,33 and 35. In the general popu-
lation, sub-clinical infection with HPV is
common and the factors which lead to
expression of the infection in the form of
genital warts are unknown. In addition,
although the entire genital tract may be
colonised by HPV, the majority of
patients have only a few warts.
Immunological factors are of impor-
tance in the expression of HPV; cutane-
ous warts are often more extensivc in
immunocompromised patients occur-
ring, for example, after renal transplan-
tation or in patients with lymphoma.
Genital warts may be larger and more
numerous during pregnancy and in
patients infected with human
immunodeficiency virus (HIV). Genital
warts of this type are not only itchy and
uncomfortable but may also bleed and
interfere with sexual intercourse. Secon-
dary infection with candida species or
anaerobic bacteria is common. Diabetic
patients may demonstrate impairment of
cell-mediated immunity and it is our clin-
ical impression that genital warts are fre-
quently more florid in affected diabetic
patients than in the non-diabetic popula-
tion (Figure 4), although no available
data on prevalence rates exists in com-
parable groups.
The treatment for genital warts which
is currently available is unsatisfactory.
The mainstay of treatment is podophyl-
lin resin, a plant extract, which is now
available in the purified form of its active
constituent, podophyllotoxin; this drug
has a cytotoxic rather than a direct antivi-
ral effect.Where genital warts are florid,
the quantity of drug required for effec-
tive treatment may cause local problems
such as burning and ulceration; rarely,
absorption of podophyllum has resulted
in systemic toxicity and caused
peripheral neuropathy. Teratogenicity
precludes the use of podophyllum during
pregnancy and in women in whom con-
traception is unreliable. Even when
warts are eradicated successfully, recurr-
ence is common.
The lack of therapeutic success may
cause serious practical difficulties in
managing some diabetic women who
have extensive genital warts.
Cryotherapy provides an alternative
method of treatment, but is generally
ineffective when the warts are florid. Sur-
gical intervention using laser ablation or
scissor excision may have to be used. The
former may cause considerable post-
operative discomfort and surgical rcsec-
tion is probably the most effective
method to remove extensive warts, par-
ticularly when this infection is associated
with recurrent metabolic upset.
Patients with warts affecting the
vagina and cervix should be examined
(and treated) by colposcopy, when any
signs of coexisting dysplastic change in
the cervix may be detected. Genital
warts in males may also prove resistant
to treatment but gradual resolution usu-
ally results from numerous applications
of podophyllum. Circumcision may be
beneficial if the prepuce is the dominant
site of warty tissue.
Other sexually transmitted diseases
frequently coexist with HPV and any
diabetic patients with genital warts
should be referred to a genito-urinary
medical clinic for exclusion of gonococ-
cal and chlamydia1 infections. The
examination and treatment of sexual
partners is also necessary.
Genital herpes
This condition is frequently confused
with candidiasis in diabetic patients, par-
ticularly when local symptoms predomi-
nate. There are two types of herpes
simplex virus, HSV-I and HSV-11. Class-
ically, HSV-I1 is associated with genital
infection, however, up to 30% of cases of
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Figure 4
Genital warts in a male diabetic patient

Figure 1
Vaginal candidiasis

Figure 2 Figure 5
Vaginal candidiasis showing adherent white plaques Primary genital herpes showing ulcer formation

Figure 3 Figure 6
Balanoposthitis caused by chronic candidiasis Resorption of the prepuce in a diabetic patient with
lichen sclerosis et atrophicus

220 Practical Diabetes November/December Vol8 No 6


________
genital herpcs is caused by Type I . The
clinical features arc divided into primary
and recurrent attacks. In primary genital
herpes there is a pre-patent period of
about seven days, following which
vesicles appear on the gcnitalia. Thcse
vesicles rupture, producing painful
ulcers (Figure 5 ) . In the female, the
lesions may coalesce, resulting in
extreme discomfort. As the mucosa sur-
rounding the urethral mcatus is frc-
quently affected, dysuria is a prominent
symptom. Lymphadenopathy and sys-
temic fcatures such as fevcr and myalgia
occur in about two-thirds o f infected
womcn and affect a smaller population
of men. In hcrpes, the predominant
symptom is pain with associated dysuria,
whereas in candidal infection, the predo-
minant symptom is itch and dysuria is
not a common feature. Becausc can-
didiasis is so common in diabetic patients
at presentation or during periods of poor
glycaemic control, the diagnosis is often
assumed without gcnital examination o r
formal invcstigation and inappropriatc
treatment is initiated. Therapeutic fail-
ure should alert the physician to an incor-
rect diagnosis in this situation.
Primary herpes is treated with acyc-
lovir tablets, 200mg five times daily for
five days. Local applications should be
avoided as they mercly increase genital
discomfort. Scverc dysuria causes diffi-
culty with micturition so that thc patient
may only be able to micturate seated in a
warm bath with sodium bicarbonatc
added to the watcr. Urethral catheterisa-
tion should bc avoided if possible as this
may aggravate thc ulceration. When a
significant systemic illncss occurs,
metabolic control of diabetes may be
scverely disturbed and admission t o hos-
pital may bc necessary to avoid or trcat
ketoacidosis*. Fortunately, the serious
systemic disturbance is usually transicnt
and thc genital lesions will heal over 10
to 14 days, but some young insulin-
treated diabetic patients are prone t o
recurrent cxaccrbations, adverscly
affecting glycacmic control.
Herpes simplex virus is transportcd to
the sacral dorsal root ganglia via
peripheral nerve fibres. The virus
remains latent but may periodically be
reactivated and travel peripherally along
the nerve onto thc skin. resulting in a
recurrence of hcrpctic lesions. Such
recurrences are usually mild and
infrequent. lasting only a few days. How-
ever, in some paticnts, rccurrent disease
may be particularly troublesomc and
further treatment with acyclovir, cither
topically or systemically, may be
required for symptomatic rclief. Rccur-
rcnt gcnital herpes in diabetic women is
frequently mis-diagnosed as candidiasis
and the (inappropriate) prescription of
antifungal agcnts is ineffective. As with
primary herpes, a history of vulva1 pain
Practical Diabetes November/December Vol8 No 6
-_-- __ _ _ _ _ - _
rather than itch can be elicited and the
clinical appearance should be easily dis-
tinguishablc from candidiasis. Systemic
upsct does not occur and glycaemic con-
trol is not disturbcd but. conversely,
ketoacidosis may precipitate recurrent
genital infection with herpes.
Human immuno-deficiencyvirus
The emergence of human immuno-defi-
ciencent virus (HIV) infection impinges
on diabetic medicinc in several ways.
Case reports have suggested that Type 1
diabetcs may be a complication o f HIV
infection3. Such cases probably repre-
sent coincidental illness, as diabetes and
HIV infections are both relatively com-
mon conditions. Furthermore, an associ-
ation of diabetcs with HIV infection
might be expected to be lcss likcly in
view of thc role of the activated immune
systcm in the destruction of pancreatic
islet cells. Little is known at present of
the effect of concurrent HIVinfection on
the natural history o f diabetcs. but it is
likely that the management of diabetcs
will be cornpromised should the patient
devclop scrious systemic infcctions as
part of the natural history of HIV infec-
tion. Peripheral ncuropathy, autonomic
neuropathy, nephropathy and rctin-
opathy (caused by infection with
cytomcgalovirus) are recognised fea-
tures of HIV infection and could potcn-
tially aggravate or bc confused with pre-
existing diabetic complications.
The most serious impact of HIV on
diabetic managcmcnt relates to the
routinc handling of blood specimens
with the risk of accidental infection with
HIV by a ncedlc stick injury or other
forms of auto-inoculation. It is likely
that the diabetic population contains
male homoscxuals and intravenous drug
addicts in a similar proportion to the
non-diabetic population and it is there-
fore inevitable that diabctic patients
with unsuspected HIV infection will be
attending routine clinics. This risk will
become greater as the virus disseminates
further into the general population and
constant vigilance is required with suita-
ble precautions for the handling o f speci-
mens from all diabetic patients. Thc
means of obtaining blood for thc routine
sidc-room measurement of plasma glu-
cose should be carefully monitored in all
diabetic outpatient clinics. Staff should
wear rubber gloves when taking capil-
lary samples of blood with a lancet and
spillage of blood should be cleared with a
disinfectant such as bleach.
Miscellaneous conditions
Lichen sclerosis et atrophicus
The aetiology of this condition, which in
men is also known as balanitis xerotica
obliterans, is unknown. It is more com-
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____ -
Review Articles
Genito-urinary disorders and diabetes
mon in women than men and usually pre-
sents in middle-agc. The characteristic
lesion. which typically affects the
genitalia but may also bc present on thc
skin of the trunk, is an ivory-white
plaque. This condition can be quite
destructive and can causc progressive
resorption o f thc prepuce in men (Figure
6). In mild cases. no treatment is
required but, in the more aggrcssivc
form, potent topical steroids are pre-
scribed. If the urethral mcatus is
involvcd, a stricture requiring surgical
intervention may result.
This condition may bc of relevance to
diabetes as affected patients havc a high
prevalence o f organ-specific antibodies
and abnormal glucose tolerance has
bcen reported in a significant proportion
of patients’.
Ery fhrasma
This is a skin infection caused by
Corynehocterium minutissimurn. Thc
appearanccs are of well-defined. red-
dish-brown, scaly patches which fre-
quently affect the inguinal area, but
other parts o f the body may also bc
involved. Affected patches havc a
Characteristic oral-red fluorescence
when viewed under Wood’s light. The
diagnosis can be confirmcd by culture
from skin scrapings and treatment is with
clotrimazolc crcam. There is a definite
association between this condition and
abnormal glucose tolerance and. in some
patients with non-insulin-dependent dia-
betes, it may be the presenting feature. It
has bcen postulated that obesity may be
a prcdisposing factor.
Lichen planus
This condition is charactcriscd by the
presence of violaccous, flat-topped
papules which may be found on any part
of thc body but frequently affect the
genitalia. The condition is thought to
represent an abnormal immune
rcsponsc, possibly to viral infection. Sev-
cral publishcd reports have associated
this condition with diabetcs and abnor-
mal glucosc tolerances.h.
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