Pustular forms of psoriasis
Neutrophilic accumulation in the epidermis is a
characteristic histological feature of all types and patterns of psoriasis, but
in clinical practice the term ‘pustular psoriasis’ is reserved for those forms
of the disease in which macroscopic pustules appear. It is convenient to
separate two main types of pustular psoriasis: localized and generalized. In
the localized forms, the disease is confined to the hands and feet and tends to
be chronic. In the generalized forms, the whole body may be involved and the
course is subacute, acute or even fulminating and life-threatening. A
convenient classification is as follows.
1.
Generalized
pustular psoriasis:
Clinical
variants (based on morphology and natural history):
i.
Acute generalized pustular psoriasis
(von Zumbusch).
ii.
Subacute annular and circinate pustular
psoriasis.
Other specified forms (based on age or precipitants):
iii.
Acute generalized pustular psoriasis
of pregnancy (impetigo herpetiformis).
iv.
Infantile and juvenile generalized
pustular psoriasis.
2.
Localized
pustular psoriasis:
i.
Palmoplantar pustulosis.
ii.
Acrodermatitis continua of
Hallopeau.
Generalized pustular psoriasis
Introduction
Generalized pustular psoriasis (GPP) is an uncommon
variant of psoriasis in which an acute, subacute or occasionally chronic
eruption has generalized sterile pustulosis as its central feature. In generalized pustular psoriasis,
the infiltration of neutrophils dominates the histologic picture, while
erythema and the appearance of sterile pustules dominate the clinical picture.
Relationship to psoriasis vulgaris
GPP is
a rare and extreme form of psoriasis in which all the main pathological
features of the disease are accentuated. Its relationship to psoriasis vulgaris
is clear, because some patients may have phases of plaque
psoriasis before or after the GPP, but
in others generalized pustular psoriasis occurs as the sole phenotype without
plaque psoriasis at any time.
Epidemiology
Incidence
and prevalence
Generalized pustular psoriasis is rare.
Age
at onset
The incidence peaks between 40 and 59 years of age, but
infantile and juvenile cases are also reported. The age
at onset tends to be earlier in those with pure generalized pustular psoriasis
without plaque psoriasis.
Gender
Women outnumber men in a ratio of about 2 to 1.
Associated
diseases
Inflammatory polyarthritis occurs in one‐third of patients. The metabolic syndrome is also frequently
associated and the reported co‐morbidities includes obesity (43%),
hypertension (26%), dyslipidaemia (26%) and diabetes (24%).
Predisposing
factors
Environmental factors that may trigger or exacerbate
generalized pustular psoriasis include infection, topical or systemic
treatments, psychological stress, pregnancy and hypocalcaemia. Provocation is
most obvious in the acute form such as in Von Zumbusch's. The most important
drug provocation is by corticosteroids. There is substantial evidence that
withdrawal of systemic corticosteroid and ciclosporin can precipitate
generalized pustular psoriasis and topical therapy with potent corticosteroids
under occlusion has also been implicated. Other systemic drugs have also occasionally
been implicated including terbinafine, propranolol, bupropion, lithium,
phenylbutazone, salicylates and potassium iodide.
Viral or bacterial infections are common exacerbating
factors in generalized pustular psoriasis. Many individuals report deterioration
at times of psychological stress. Hypocalcaemia may arise as a consequence of
generalized pustular psoriasis, but triggering of active disease by
hypocalcaemia caused by hypoparathyroidism has also been reported. Generalized
pustular psoriasis is also triggered by pregnancy.
HLA antigens
There is a strong positive correlation of GPP with
HLA-B27. The association of GPP with polyarthritis may partly explain this
finding.
Histopathology
In acute GPP, there is intense inflammation. The earliest infiltrate
is lymphocytic. Intense papillary and epidermal edema causes spongiosis. The
arrival of masses of neutrophils leads to spongiform pustule formation (Kogoj)
and abscesses that quickly become macroscopic. There is acanthosis with
elongation of rete ridges. The stratum corneum soon becomes parakeratotic and
the subcorneal pustule is shed as epidermal turnover is accelerated.
Essentially, the same features are seen in subacute as in acute patterns but in
a less intense form.
Clinical
features
History
In the acute stage, there is a burning painful sensation in
the skin, usually without a prodrome. Fever and malaise accompany the
development of waves of pustules. About a third of patients complain of
arthralgia.
Clinical variants (based on morphology and natural history)
Acute generalized pustular psoriasis (von Zumbusch)
This is the most acute and severe form of generalized
pustular psoriasis. It may occur as the sole phenotype or arise following
plaque psoriasis, acrodermatitis continua of Hallopeau or palmoplantar pustulosis.
It may manifest only in pregnancy when it has been referred to as impetigo
herpetiformis, and may be the phenotype in infantile and juvenile generalized
pustular psoriasis. Diagnostic criteria have been proposed consisting of
recurrent episodes of fever with general malaise, multiple isolated sterile
pustules, laboratory abnormalities (leukocytosis, elevated erythrocyte
sedimentation rate or C‐reactive protein), supported by Kogoj's spongiform pustules
on histopathology.
Two main groups have been distinguished. In one, plaque
psoriasis of early onset develops into pustular psoriasis often after many
years, and sometimes provoked by corticosteroid withdrawal or other external
factors. In the other, which is less closely related to plaque psoriasis, the
onset of pustular psoriasis arises de novo, sometimes provoked by
infection. It may be atypical initially, restricted to acral or flexural sites
but rapidly and spontaneously progresses to the generalized pustular form.
In either form, the generalized eruption may be ushered in
by a sensation of burning in the skin, which becomes dry and tender. These
warning signs – not always present – are followed by an abrupt onset of high
fever and severe malaise. The constellation of fiery-red erythema followed by
eruption of monomorphic non‐follicular pinpoint sterile pustules
over a period of less than 1 day. Patients are frightened and toxic. Nikolsky
sign is positive. The pustules are disseminated over the trunk and extremities,
including the nail beds, palms and soles. The pustules usually arise on highly
painful erythematous skin, first as patches and then becoming confluent as the
disease becomes more severe. Flexural and anogenital accentuation may be present. Any configuration of pustular exanthem may occur, for
instance isolated pustules, lakes of pus, circinate lesions, and plaques of
erythema with pustular collarettes. The erythema that surrounds the pustules often
spreads and becomes confluent, leading to erythroderma. Characteristically, the
disease occurs in waves of fever and pustules. After several days, the pustules
dries up
and extensive exfoliation results.
There is onycholysis and shedding of the nails caused by
subungual lakes of pus. With prolonged disease, the fingertips may become
atrophic. The buccal mucosa and tongue may be involved, the lesions on the
latter being clinically and histologically indistinguishable from geographic
tongue. Remission may occur within days or weeks, the psoriasis returning to
its normal state, or erythroderma develops. Relapses are common.
Subacute annular generalized pustular
psoriasis
Annular lesions may be seen in acute generalized pustular
psoriasis (von Zumbusch), but are more characteristic of the rarer subacute or
chronic forms of widespread pustular psoriasis. This is a common presentation
of generalized pustular psoriasis in infancy and early childhood. Lesions begin
as discrete areas of erythema, which become raised and edematous. Slow
centrifugal spread produce annular lesion. Pustules appear peripherally on the
crest of the advancing edge, become desiccated and leave a trailing fringe of
scale as the lesion slowly advances. There are generally no systemic symptoms.
Other specified forms of generalized pustular psoriasis
(based on age or precipitants)
Acute generalized pustular psoriasis of
pregnancy (impetigo herpetiformis)
Definition
A rare eruption, impetigo herpetiformis represents generalized pustular
psoriasis triggered by or occurring in pregnancy, with the features of generalized
pustular psoriasis, but with a tendency to be symmetrical and grouped, and
often starting in the flexures. Constitutional disturbance may be severe.
Clinical features
Onset is usually in the last trimester of pregnancy. The
disease tends to persist until the child is born, and occasionally long
afterwards. Essentially, the features are of generalized pustular psoriasis,
usually of flexural onset and with a marked tendency to symmetry, and sometimes
grouping of areas of pustulation. The eruption usually starts in the inguino‐genital region and other flexures, with minute pustules
arising on an acutely inflamed skin. These extend centrifugally, drying in the center, or form plaques
in which eroded greenish yellow pustules become fetid, crusted or vegetating.
Condyloma like lesions may form in the flexures. The eruptions may become
widespread. As individual areas heal, they
leave a reddish brown pigmentation. The tongue, buccal mucosa and even the esophagus
may be involved, with erosive lesions following short‐lived pustules.
Constitutional disturbance is characteristically severe with
fever, and death may occur due to cardiac or renal failure. Rarely
tetany, delirium, and convulsions occur, if the hypocalcemia is severe. The more severe and longstanding the disease, the greater
the risks of placental insufficiency, that leads to stillbirth, neonatal death
or fetal abnormalities.
Characteristically, the disease recurs in subsequent pregnancies.
Infantile and juvenile generalized pustular psoriasis
All forms of pustular psoriasis are rare in childhood.
Although GPP can begin at any age in childhood, in over 25% of cases onset is
in the first year. In contrast to psoriasis vulgaris in childhood and GPP in
adults, a male preponderance is seen in GPP of childhood (about 3: 2).
Infantile cases are usually benign because systemic symptoms are often absent
and spontaneous remissions occur. Pustular
psoriasis may be localized to flexural areas, for instance the neck, for long
periods.
The majority of children are aged 2–10 years at onset.
The disease may be of Zumbusch pattern, but annular and circinate forms are more common in this age group.
Classification
of severity
The activity of disease at a given time point has been
categorized as mild, moderate or severe based upon the extent of erythema and
pustulation, fever and laboratory abnormalities (leukocytosis, elevated
inflammatory markers, low serum calcium and albumin).
Complications
and co‐morbidities
In the acute phase, the affected individual is systemically
unwell. Hypovolaemia and oligaemia can cause acute kidney injury.
Hypoalbuminaemia in the acute episode may be profound, perhaps because of a
sudden loss of plasma protein into the tissues and intestinal malabsorption.
Hypocalcaemia may arise as a consequence of the hypoalbuminaemia and
malabsorption. Abnormalities of liver
enzymes are common, occurring in up to a half of patients during the acute
episode. Cholestatic jaundice may arise as a consequence of neutrophilic
cholangitis. Acute respiratory distress syndrome (psoriasis‐associated aseptic pneumonitis) is rare. It presents with
rapidly deteriorating dyspnoea and hypoxia in the absence of infection and responds
to oral corticosteroids. Staphylococcus aureus may occasionally be grown
from pustules and rarely from blood cultures. If generalized pustular psoriasis
lasts more than a few days, hair loss may follow from all areas of the body.
Telogen effluvium may follow 2–3 months after the height of the illness.
Disease
course and prognosis
In the absence of effective treatment, death can occur in
the acute stage. The prognosis is good for subacute annular and circinate
generalized pustular psoriasis.
Amongst generalized pustular psoriasis (von Zumbusch) the
prognosis is better when there is a clear trigger, exemplified by generalized
pustular psoriasis of pregnancy. Generalized pustular psoriasis developing from
acrodermatitis continua of Hallopeau seems to have the worst prognosis as it
affects the elderly.
Investigations
The erythrocyte sedimentation rate and C‐reactive protein are usually raised. There may be an
absolute lymphopenia at the onset of generalized pustular psoriasis. A
polymorphonuclear leukocytosis quickly follows. Plasma albumin, zinc and
calcium may be abnormally low. Malabsorption may explain some of these
findings.
Management
The treatment of acute generalized pustular psoriasis often
requires in‐patient dermatological management with topical and usually
systemic drug therapy, general supportive measures and removal of possible
provocative factors. Excessive heat loss must be prevented by maintaining an
adequate ambient temperature. Fluid intake should be increased so that the
daily urine volume remains adequate. Tar or dithranol can be withdrawn
abruptly, but removal of potent topical corticosteroids requires more care. The
application of serially diluted topical corticosteroids over several days may
be the safest course. Infection, where present, should be treated rigorously
with the appropriate antibiotics. In rare circumstances, when generalized
pustular psoriasis in pregnancy is threatening maternal life, termination or
early delivery may be indicated.
If there is no immediate metabolic threat in acute
generalized pustular psoriasis, and generally in subacute forms, initial
treatment should be conservative. This is particularly so in infancy and
childhood. Bed rest in hospital, mild sedation and bland local applications
with fluid and protein replacement may promote spontaneous reversion to a
quieter erythrodermic psoriasis or even plaque psoriasis.
Topical
treatment
Often, bland creams or lotions are best. Weak corticosteroid
creams may be helpful in subacute forms. Tar and dithranol are contraindicated.
Systemic
therapy
Most cases of generalized pustular psoriasis require
systemic therapy. Oral retinoids are probably the treatment of choice.
Acitretin is effective in more than 80% of cases, and is more effective than
oral corticosteroids, methotrexate or ciclosporin. High doses of acitretin (1
mg/kg/day) should be given for rapid control in severe generalized pustular
psoriasis and lower doses of 0.5–0.75 mg/kg/day may be sufficient in milder
disease and to maintain remission. Acitretin should not be used for generalized
pustular psoriasis of pregnancy.
Rapid control of generalized pustular psoriasis can be
achieved with high‐dose ciclosporin and remission maintained with a lower dose.
Doses in the range of 3.5–5 mg/kg/day are recommended. Methotrexate is
effective in about 60% of patients but has a relatively slow onset of action.
Oral methotrexate needs to be dosed with caution in those with severe disease,
because of concerns about erratic absorption. Parenteral administration should
be considered. An oral dose of 0.2–0.4 mg/kg/week should suffice, starting at
the lower end of the range. If the patient is very ill, renal function should
be monitored frequently if methotrexate over dosage is to be avoided.
Methotrexate has been used with success in children with generalized pustular
psoriasis. Oral or parenteral corticosteroids should generally be avoided and
used only when urgent control of complications is needed (e.g. acute
respiratory distress syndrome) or when other drugs are contraindicated, for
instance in pregnancy. The short‐term
effects of prednisolone (30–40 mg/day) are good, but serious relapses are
liable to occur as the dosage is reduced unless another form of therapy (e.g.
acitretin, TNFi) is given simultaneously.
Therapeutic ladder
First line
·
Acitretin (not in generalized
pustular psoriasis of pregnancy)
·
Ciclosporin
·
Methotrexate
Second line
·
Infliximab
·
Adalimumab
·
Etanercept
·
Prednisolone (special circumstances
only)
Third line
·
Anakinra
Palmoplantar pustulosis
Definition
This is a common condition in which
erythematous and scaly plaques studded with sterile pustules persist on the
palms or soles. The disease is chronic, very resistant to treatment and
probably a separate disease to plaque psoriasis.
Epidemiology
Incidence
and prevalence
The prevalence is estimated at
0.01–0.05% of the general population.
Age
at onset
Peaks occur between the ages of 30
and 50 years, later than for plaque psoriasis.
Gender
Women are more affected than men, in
a ratio of about 5: 1.
Associated
diseases
Certain
conditions have been reported to occur in patients with palmopustular pustulosis
more often than in unaffected patients.
Chronic plaque psoriasis (10–25% of patients)
Autoimmune diseases
particularly gluten sensitive enteropathy (celiac disease), thyroid disease and
type 1 diabetes.
Streptococcal
tonsillitis.
Rarely,
synovitis–acne–pustulosis–hyperostosis–osteomyelitis (SAPHO) syndrome.
Palmoplantar
pustulosis may rarely be provoked by the tumour necrosis factor alpha
inhibitors (infliximab, adalimumab, etanercept).
A significant prevalence of
autoimmune thyroid disease and the presence of thyroid antibodies have been
found in association with palmoplantar pustulosis. Some patients also have
antigliadin antibodies and show an improvement in palmoplantar pustulosis on a
gluten‐free diet. Palmoplantar pustulosis is the commonest
cutaneous manifestation of a group of rare diseases known as SAPHO syndrome
(synovitis, acne, pustulosis, hyperostosis and osteitis; syn. pustuloticarthro‐osteitis). This most frequently involves the anterior chest
wall but may also involve the axial skeleton.
Predisposing
factors
Palmoplantar pustulosis usually
starts without obvious provocation. Cigarette smoking has been reported to be
strongly associated – more than 90% of patients with palmoplantar pustulosis
are current or previous smokers and in some instances the disease improves in
those who manage to stop smoking. It is thought that activated
nicotine receptors in the sweat glands cause an inflammatory process.
Histopathology
Histologically,
there is an intraepidermal cavity filled with polymorphonuclear leukocytes
associated with spongiform changes within the surrounding epidermis.
Eosinophils and mast cells are present in increased numbers in PPP biopsies
from lesional skin. Another hallmark is the inability to visualize the
epidermal part of the eccrine duct in PPP specimens indicating an involvement
of the acrosyringium
Causative
organisms
The pustules in palmoplantar pustulosis
are sterile. Distant septic foci, particularly in the tonsils or oro‐pharynx, with an increased production of cutaneous
lymphocyte‐associated antigen (CLA) positive T cells in the tonsils are
found in patients with palmoplantar pustulosis.
Resolution of palmoplantar pustulosis occurs in up to 60% of cases following
tonsillectomy.
Clinical
features
The disease presents with one or
more well‐defined plaques. On the hands, the thenar eminence is the
most common site. Less commonly, the hypothenar eminence or the central palm or
the distal palm are involved. On the feet, the instep, the medial or lateral
border of the foot at the level of the instep, or the sides or back of the heel
are involved. Less frequently, the distal sole or the whole sole is implicated.
Digital lesions are uncommon. A striking symmetry of the lesions on the hands
or feet is common, but
unilateral location on palms and/or soles can be seen.
The affected
area is dusky red and scaly, and fissures may develop. Removal of scale (e.g.
by treatment) leaves a glazed dull‐red surface. Within this plaque, numerous pustules of
nearly equal size measuring two to four mm in diameter are present. Normally, pustules in
all stages of evolution are seen. Sometimes, the pustules
extend to the dorsa of the fingers, the feet, or over the volar wrists.
Episodes of new pustular eruptions occur at varying intervals and remain
strictly confined to the sites of predilection. Fresh pustules are yellow and as the pustules become
older, its content dries up and their yellow color changes to dark brown, so
that in untreated PPP, the lesions show various shades of color. Within several
days after pustule formation, lesions dry, flatten, and acquire a brownish
color. This may be followed by eczematous changes with scaling and fissuring. Dried
pustules are shed within approximately 8 to 10 days.
Symptoms include itching or a burning sensation, which
may precede new crops of lesions. However, in severe eruptions, pain and the
inability to stand, walk, or do manual work may greatly reduce the quality of
life.
In contrast to the natural history
of generalized pustular psoriasis, the pustules remain localized to the palmoplanter
surfaces.
Diagnosis and
Differential Diagnosis
PPP is a distinct entity. The course of the disease,
together with the characteristic morphology, permits the proper diagnosis. The
disease must be differentiated from dyshidrotic eczematous dermatitis
(pompholyx), especially when pustules due to secondary infection are present.
In that condition, the onset is also acute, but clear vesicles of various sizes
are scattered on the palms, soles, and volar and interdigital aspects of the
fingers. These may coalesce and secondarily become pustular because of
secondary bacterial infection.
Pustular variants of tinea of the palms and soles or
pustules developing in infected scabies may resemble PPP. Bacterial cultures or
demonstration of hyphae or mites clearly separate these entities from PPP. Allergic contact dermatitis caused
by rubber in footwear should not cause diagnostic difficulties: typically the
insteps are spared.
Prognosis/Clinical
Course
The clinical course of PPP is highly unpredictable. In
patients with active disease with ongoing development of fresh pustules at the
beginning of treatment relapse within a few days after cessation of any therapy
or dose-reduction is highly likely. In phases of remission fewer pustules are
produced, but the skin may remain erythematous and hyperkeratotic, sometimes
resembling eczema. Cessation of smoking may help to extend disease-free
intervals and to decrease activity of PPP.
Treatment
PPP is
difficult to treat and all reported treatments have a high recurrence rate. Treatment is often as disappointing for the physician as for
the patient.
Treatments for Palmoplantar Pustulosis and Acrodermatitis Continuaa
|
Topical |
Physical |
Systemic |
|||
|
First line |
Potent and superpotent steroids |
bid, plastic film occlusion |
PUVA Bath—4/week |
Acitretin |
0.5 mg/kg/day |
|
Second line |
Methotrexate Cyclosporine |
10–25 mg/wk 2.5–5 mg/kg/, when effective individual titration of
dose |
|||
|
Third line |
Biologics |
Dosing as recommended for psoriasis |
Topical
therapy
In
patients with limited disease or only focal lesions, topical therapy with superpotent
corticosteroids applied twice daily is the
treatment of choice. Increased efficacy can be obtained by occlusive therapy
with potent steroids. There are no
published controlled trials to support the efficacy of calcipotriol, coal tar,
dithranol or tazarotene.
When PPP involves larger parts of palms and/or soles
systemic treatment with or without additional topical therapy should be
initiated.
Phototherapy
Psoralen
plus ultraviolet A (PUVA) therapy, narrow band ultraviolet B (NB-UVB)
phototherapy, and excimer light therapy are all used in the treatment of PPP.
They are well-tolerated, with the most common side effects being transient
superficial skin erythema, burn, and pain. Most studies describe PUVA therapy. Oral
PUVA is often effective in improving palmoplantar pustulosis and will sometimes
clear the disease temporarily; the response is enhanced by combination with an
oral retinoid (re‐PUVA), which can produce remission in up to 60% of people.
The monochromatic excimer light (MEL) device delivers a UVB
wavelength at 308 nm only to the lesional skin, and seems particularly
effective for variants of psoriasis were the involvement of the skin is lower
than 20-25% of the total body surface. Moreover, it is highly effective with relative
rapidity of action and safe. Its high potency (up to 4.5 J/cm2) and
subsequently the need for short time of irradiation, together with the
possibility to schedule just 1 session per week, makes MEL mostly appreciated
to a large part of patients, thus increasing treatment compliance.
Systemic
therapy
Systemic therapies offer the best
opportunity for remission. First-line systemic treatment includes
acitretin at a dose of 10 mg to 50 mg per day, with a maximal effect seen
between three and six months after initiation of treatment. Oral retinoids have established efficacy for induction of
remission and also as maintenance therapy. Acitretin is
contraindicated in pregnancy.
Second-line systemic agents include methotrexate and cyclosporine.
Methotrexate is dosed at 7.5 mg to 20 mg per week over three to six weeks. Methotrexate has
lower efficacy in PPP and is used mainly in patients with concomitant psoriatic
arthritis. Cyclosporine can be used in immunocompetent patients with severe
recalcitrant palmoplantar psoriasis. Response
rates with cyclosporine are higher. Most patients will respond in the short
term to cyclosporine 2.5 mg/kg/day and some patients can be maintained on doses
as low as 1 mg/kg/day. The dose should be tapered rather than stopped abruptly
in view of rare instances of provoking generalized pustular psoriasis.
Methotrexate is contraindicated in pregnancy, while cyclosporine
can be used with caution.
Biologics
Biologics are reserved for patients who fail or cannot complete
treatment with topical or other systemic medications. Etanercept is a TNF-a inhibitor
that showed a statistically significant reduction in PPPASI with 50 mg twice
weekly for 24 weeks of therapy. Similarly, infliximab dosed at 5 mg/kg at
weeks zero, two, and six, and then every eight weeks showed a 50% reduction in
the mean surface area of the palms and soles. Adalimumab treatment with 40
mg given subcutaneously (SC) every two weeks for a total of three months
demonstrated improved quality of life in studies. Ustekinumab is an IL-12
and IL-23 inhibitor dosed at 45 mg (less than 100 kg) or 90 mg SC (100 kg or
more) every three months that resulted in complete clearance in 35% of patients
at 16 weeks. Secukinumab is an IL-17A inhibitor dosed at 300 mg (90 kg or
more) or 150 mg SC (<less than 90 kg) every week from baseline to week three
then every four weeks. Thirty-three percent and 22.1% of patients were clear or
almost clear at week 16 with 300 mg and 150 mg, respectively. Ixekizumab is
another IL-17A inhibitor that is dosed at 160 mg SC at week zero than 80 mg
every two weeks up until week 12 then 80 mg every four weeks. PPASI
100 was achieved in 50% of patients treated with ixekizumab in studies.
Many patients with psoriasis have other co morbidities such as
renal failure, liver disease, malignancy or heart failure, which also predispose
them to adverse effects from the medications. Hence, a careful risk versus
benefit ratio must be performed for each patient before initiating treatment.
Prevention
Cessation of smoking and, according to data mainly
generated in Asian countries, tonsillectomy may help to prevent new eruptions
of PPP. In patients tested positive for antigliadin and/or tissue
transglutaminase antibodies and/or with proven celiac disease a gluten-free
diet seems to be a preventive measure.
Acrodermatitis continua of Hallopeau
Introduction
Acrodermatitis
continua of Hallopeau (ACH) is a rare inflammatory disease characterized by sterile pustular eruptions beginning in the tips of fingers and
toes (digits) that tends slowly to extend locally
but which may evolve into generalized pustular psoriasis. The pustules may vary
in extent over a chronic, recurrent course. The disease is named after the
French dermatologist François Henri Hallopeau, who described the syndrome in
1880.
Patients with
acrodermatitis continua of Hallopeau do not usually have additional plaque
psoriasis. The distribution of lesions in acrodermatitis continua of Hallopeau
is distinctive. Continuous pustulation leads to nail
destruction and atrophy of the distal phalanx.
Epidemiology
Age
at onset
Whereas
PPP is a disease of middle life, acrodermatitis may be seen in children. It is rare in young adults and, unlike palmoplantar pustulosis,
frequently begins in old age.
Gender
It is more common in women.
Associated
diseases
Clinical features may overlap with
palmoplantar pustulosis, and may evolve into generalized pustular psoriasis.
Environmental
factors
The onset is often attributed by the patient to minor
trauma, or infection at the tip of the digit. It may be precipitated or
aggravated by oral corticosteroids.
Histopathology
The features
are similar to those of generalized pustular psoriasis. In the epidermis, there
are numerous subcorneal neutrophilic pustules and spongiform pustules with
hypergranulosis and parakeratotic hyperkeratosis. There
is a moderate lymphohistiocytic infiltrate in the upper dermis, together with
focal edema.
Lesions of long duration show severe atrophy of the
papillary dermis and thinning of the epidermis.
Clinical
features
ACH most often begins at the tips of one or two fingers or thumb,
less often on the toes. The nail folds are affected very early, and trauma is
thought to play an initiating role. The
skin over the distal phalanx becomes red and scaly, and micro pustules develop,
which, on bursting, leave a bright
red,
shiny area in which new pustules develop. These then tend to coalesce, forming
polycyclic lakes of pus. As the disease extends proximally, the affected area
shows either glossy erythema or a crusted, keratotic, and fissured surface with
newly formed pustules underneath. Pustulation of the nail bed (beneath the nail
plate) and the nail matrix almost always occurs and quite often leads to loss
of the nail plate or severe onychodystrophy. Acrodermatitis continua of long
duration may show complete destruction of the nail matrix and thus lead to
anonychia. The skin becomes shiny and severely atrophic, and there is atrophic
thinning of the distal part of the phalanx. As a result, the free end of the digit may become
wasted and tapered, mimicking scleroderma. In such digits, the circulation may
be secondarily affected so that discomfort is greatest in cold weather. Eventually,
other digits may be involved.
The disease may remain confined to the original site,
sometimes up to several years, but more often it spreads proximally to cover
the hand, dorsum of forearm, or foot. In such instances more than one extremity
is involved.
Acrodermatitis
continua of Hallopeau may evolve into generalized pustular psoriasis of
the Zumbusch type,
especially in the elderly. The disease may also affect mucosal
surfaces such as the conjunctiva, tongue and urethra. The tongue may show
annulus migrans of pustular psoriasis.
Investigations
ACH
is diagnosed based on clinical presentation and histological appearance of a
skin biopsy
examined under the microscope. The pustules are sterile. In advanced cases,
X-ray may reveal atrophy of the distal phalanx and arthropathy of the
interphalangeal joints.
Differential Diagnosis
Acrodermatitis continua at an early stage must be
differentiated from acute paronychia caused by bacteria or fungi and from
herpetic lesions. Cultures and smears help rule out infectious causes. The
distal localization and the tendency of the pustules to become confluent, which
on bursting forming denuded, erythematous, or crusted lesions, distinguishes
acrodermatitis continua from pustular dyshidrotic eczema. Atrophy and loss of
nails do not occur in this condition. Contact dermatitis with secondary
infection and pustulation has less clearly defined margins, runs a different
clinical course, and lacks the persistence typical for acrodermatitis continua.
The most important condition
to compare and contrast with ACH is PPP. Fortunately, several key features help
distinguish these related conditions. First, ACH often follows trauma, as
previously described, whereas PPP rarely involves a history of injury. Second,
suppurative nail involvement is an early and defining feature of ACH whereas
PPP does not always affect the nails and is usually
non-suppurative. Third, ACH most commonly remains unilateral and localized
to a limited number of digits and with an irregular distribution for many
years, while PPP is most commonly bilateral and symmetrical. Lastly,
features such as soft tissue sclerosis and osteolysis as described in ACH are
not reported in PPP.
Prognosis/Clinical
Course
Acrodermatitis continua show a chronic course with a
tendency of the lesions to spread proximally. Spontaneous improvement is rare,
and episodes of acute pustulation occur without apparent cause. The development
of pustules at other sites, or even the eruption of generalized pustular psoriasis,
supports the idea that ACH is a variant of psoriasis. When uncontrolled,
irreversible destruction of the complete nail apparatus occurs.
Treatment
ACH is often refractory to treatment. As in pustular
psoriasis, no specific drug is able to induce lasting remissions. Potent or
superpotent topical steroids, preferentially under occlusion, are useful in
blocking pustulation. Caution is advised in cases already showing atrophy. PUVA
suppresses the eruption of new pustules and can be employed for long periods as
maintenance treatment.
Treatment
with a combination of systemic acitretin and local
calcipotriol/calcipotriene
may be useful. In recalcitrant patients, dapsone may be tried.
Recently, topical treatment with tacrolimus 0.1% ointment alone
or in sequential combination with calcipotriol is found successful. Acitretin or cyclosporine may be effective in
some patients.
In recent years, the introduction of biologics has provided a new
class of therapy that has revolutionized the treatment of
ACH. Specifically, rapid and sustained responses have been reported with the
use of anti-TNF agents like infliximab, adalimumab, and
etanercept, IL-17 inhibitors like secukinumab, and IL-12/23 inhibitors like ustekinumab. With respect to the
recalcitrant nature of the diseases combination therapy of adalimumab, etanercept, or infliximab with either
acitretin or methotrexate may be advisable in
order to maintain treatment response when stopping anti-TNF-α-therapy while
continuing acitretin or methotrexate.
There is a report of the rapid clearance of pustules within 24 h of starting
the IL‐1 receptor antagonist anakinra in a patient who was
resistant to adalimumab and ustekinumab.
In principle, regimens used for treatment of PPP may also
be used for therapy of acrodermatitis continua. The therapeutic result lasts as
long as the drugs are given, and relapses occur after withdrawal.
Therapeutic ladder
First line
·
Super‐potent topical corticosteroid ± occlusion
Second line
·
Acitretin
·
Ciclosporin
·
Adalimumab
