A transient pruritic eruption exacerbated by heat

A TRANSIENT PRURITIC ERUPTION EXACERBATED BY HEAT

History
A 26-year-old woman attends the dermatology clinic complaining of a 4-month history of
an itchy eruption. She describes the eruption as ‘cloud-like’. She previously suffered from
eczema as a child but this rash is different. She tells you that although the eruption waxes
and wanes, with individual lesions lasting 8 to 12 hours, she is rarely clear of lesions for
more than half a day. Sometimes she goes to bed with the eruption and wakes clear, but
the opposite can also occur. She has never experienced angioedema. She tells you it is often
worse peri-menstrually. You question her about possible precipitants; she tells you that the
eruption is worse with exercise or a hot bath, but does not appear to be aggravated by pressure
or cold. The eruption is partially attenuated by cetirizine 10 mg daily, which she is taking
for her hayfever. Her only other medication is occasional ibuprofen for dysmenorrhoea.
There is no family history of skin lesions. Both of her parents are well, although her
mother has a diagnosis of osteoporosis and is on thyroxine replacement. On close questioning
she admits that although circumstances at work are stable and have not changed
for a longtime she is experiencing difficulty coping and frequently cries at work.
Examination
On examination there are several scattered lesions over her trunk, limbs and face. They are
composed of well-defined erythematous oedematous plaques surrounded by a pale ‘flare’
(Fig. 9.1). The lesions vary in size and shape but not in morphology. You are unable to
elicit dermographism. The lesion that you ringed initially had disappeared by the time she
presented to photography 2 hours later, with new lesions developing over adjacent skin.
Following their resolution the lesions leave no
persistent skin change. Although the eruption is
pruritic there is no evidence of lichenification or
excoriations. Her blood pressure is 105/68 mmHg
and pulse rate 102 beats/min. Examination of
her cardiorespiratory system is otherwise normal.
Her abdomen is soft and non-tender. You notice
a degree of bilateral upper eyelid lag. She has
a smoothly enlarged goitre and stretching her
hands out she has a fine tremor.
Examination of the remainder of the neurological
system is normal. Urinalysis was negative for
blood, white cells and glucose. You ask the patient
to put on her coat and walk briskly up and down
the corridor outside. After five minutes she returns
with a marked aggravation of her eruption, which
is now widespread and generalized over her
trunk and proximal limbs. You draw around a
well-defined skin lesion and request some further
investigations

Full blood count Normal
Urea and electrolytes Normal
Liver function tests Norma

Questions
• What is this eruption?
• What factors in the history and on examination might be contributing to the eruption?
• How would you investigate this patient?
• What is the management?

This patient is suffering from urticaria, which is characterized by wheals or ‘hives’ that
represent areas of cutaneous mast cell degranulation, releasing histamine and other
mediators, followed by transient oedema and erythema. When urticaria persists for more
than 6 weeks it is classified as chronic urticaria. It represents a tissue reaction pattern and
can be precipitated by a variety of stimuli or triggers. Many skin eruptions are known
which may present with ‘urticated’ lesions that are not transient.
There may be more than one precipitant of urticaria in any one affected individual.
Although there is an element of physical provocation, which you have demonstrated by
exercising the patient, the eruption can be present on waking and therefore there is more
to this than cholinergic urticaria. The patient is atopic, a factor reported to be associated
with urticaria. She has made an interesting observation that her urticaria is worse
peri-menstrually; the phenomenon of progesterone-provoked urticaria is described. It
is more likely, however, that the exacerbation is due to her use of a non-steroidal antiinflammatory
drug (ibuprofen). Importantly, she has clinical features of thyrotoxicosis –
chronic urticaria is associated with a number of autoimmune diseases, particularly
autoimmune thyroid disease (Graves’ disease), systemic lupus erythmatosus (SLE) and
cryoglobulinaemia.
Urticarial vasculitis is an important differential diagnosis of chronic urticaria. Typically
the lesions of urticarial vasculitis are associated with a burning pain and persist for more
than 24 hours. They may leave post-inflammatory hyperpigmentation or ecchymoses on
resolution and can be diagnosed by the demonstration of a leucocytoclastic vasculitis on
biopsy of affected skin. Where urticarial vasculitis is suspected a work-up for potential
systemic vasculitis is important.
The initial investigation of this patient would include complete blood cell count, erythrocyte
sedimentation rate, thyroid function tests, antithyroid antibodies (antithyroid
microsomal and peroxidase antibodies), basophil histamine release assay. Other tests
which might be considered: skin biopsy, antinuclear antibodies (ANA), C3, C4 (if features
of urticarial vasculitis or associated angioedema suggesting acquired C1 esterase deficiency
secondary to SLE), cryoglobulins and cryoprecipitans (if history of cold-induced
urticaria).
It is clear that this patient has symptomatic thyrotoxicosis, so its management and
control may significantly improve or even resolve her urticaria. In the short term propranolol
may be indicated until carbimazole achieves a euthyroid state. For any persisting
urticaria non-sedating antihistamines (anti-H1) are the mainstay of treatment. Response
to different antihistamines can vary so it may be worthwhile trialling different agents,
and in some cases doses higher than those required in allergic rhinoconjunctivitis may
be needed. The addition of anti-H2 antihistamine such as ranitidine or cimetidine may
provide some additional blockade of histamine receptors and can be beneficial, as can the
addition of a leukotriene receptor antagonist such as montelukast. In general these agents
are well tolerated. For patients with evidence of autoimmune association and troublesome
persistent urticaria, immunosuppressive therapy with agents such as ciclosporin or methotrexate may be required.