CHAPTER 21

Pustular Eruptions of Palms and Soles

Ulrich Mrowietz
Pustular eruptions of the palms and soles include palmoplantar pustulosis (PPP), acrodermatitis continua (Hallopeau disease), and infantile acropustulosis (Table 21-1). The entities present with chronic and persistent eruptions of sterile, purulent vesicles.

PALMOPLANTAR PUSTULOSIS

Studies from Japan provide evidence for phenotypic and genetic heterogeneity of PPP according to its association/ provocation with tonsillitis. In patients in which PPP was not associated with tonsillitis, the phenotype frequency of the TNF-132 allele of the TNE-figene and of the allele B of the TNF-a gene (TNF-a pB) was significantly higher as compared to controls.5 These findings further substantiate the notion that PPP and psoriasis represent different entities.

Chronic inflammatorydisorderwith sterile pustule formation. Affects only palms and soles. Disabling in severe cases. High rate of recurrence. Often resistant to treatment. Can be part of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome.

Etiology
The cause of PPP is not known. An imbalance of the protease/antiprotease system in the skin consisting of decreased antileukoprotease (elafin/SKALF') activity in pustular psoriasis has been discussed as a possible mechanism of pustule formation. 6 Exacerbation of PPP has been observed after patch testing with metals and was accompanied by elevated leukotriene B4 levels in plasma and pustules? In a long-term survey from Japan, the incidence of PPP was found to be positively correlated to heavy smoking (more than 20 cigarettes per day), tonsillitis, and seasonal factors such as high humidity and high temperature 3,9 The most striking association in PPP is smoking. In two Swedish surveys, 95 percent of PPP patients were smokers at onset of disease and cessation of smoking was the most important measure to treat the disease.1101 There is evidence from immunohistochemical studies that nicotinic acetylcholine receptors are modulated in lesional skin from smoking PPP patients when compared to smokers and healthy controls suggesting an abnormal response to nicotine in PPP.12 Case reports have revealed multiple provocation factors of PPP including thyroid-diseases,13 Helicobacter pylori infection,14 and psychologic factors such as anxiety.

PALMOPLANTAR PUSTULOSIS

PPP is a chronic pustular dermatosis

localized on the palms and soles only. High resistance to treatment and a high recurrence rate are characteristic. Histologically, it is characterized by intraepidermal vesicles filled with neutrop hits. Previously, PPP was classified as a form of pustular psoriasis and many textbooks describe PPP in their respective chapter of psoriasis. Today, PPP is regarded as its own entity. The involvement of palms and soles has a great impact on life quality and the ability to work.

Genetics
I-E.A typing of patients with PPP reveals no increased frequency of any of the known psoriasis-linked alloantigens.1 In a direct comparison among chronicplaque psoriasis, guttate psoriasis, and PPP, the three major candidate genes within the PSORS1 region (ALA-Cw6, HCR*VVVVCC, and CDSN*5) showed a high association to guttate and chronic plaque psoriasis, not, however, to PPP.2 Investigation of the apolipoprotein E alleles e2, e3, and e4 in chronic plaque and guttate psoriasis as well as in PPP in acitretin responders and nonresponders showed that the frequency of the e4 allele was significantly higher in the psoriasis groups but not in PPP patients as compared to healthy controls.3 In chronic plaque psoriasis and psotiatic arthritis an association with tumor necrosis factor (TNF)-a-238 and -308 promotor polymorphisms have been found; however, the association has not been found in PPP.4

S E L O DS N SA M L A FP SO N O I T P U R RE EA U T S U P

Epidemiology
PPP has a worldwide distribution. It is a tare condition, but the exact incidence is not known. Females show a higher prevalence than males, with a ratio of approximately 3:1. Onset of the disease occurs mostly between the ages of 20 and 60 years; rarely, the condition occurs after the sixth decade of life, and in 10 percent of the patients the onset is before the age of 20 years.
TAB LE 21 -1
Pustular Eruptions of Palms and Soles

STERILEPUSTULESON
Palmoplantar pustulosis
PALMS AND SOLES Yes AGE

Cur wous ATROPHY

ASSOCIATED DISEASE

HISTOLOGY

Adults

Absent

Acrodermatifis continua (Hallopeau) Infantile acropustulosis (see Chap. 106)

Yes Yes

Adults Infants

Present Absent

Psoriasis, SAPHO (synovifis, acne, pustulosis, hyperostosis, osteitis) syndrome Pustular psoriasis, Zumbusch type Absent

Spongiform pustule, neutrophils, some eosinophils Spongiform pustule, neutrophils Subcomeal pustule, neutrophils, some eosinophils

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Clinical Features
The primary lesions are pustules of nearly equal size measuring two to four mm in diameter. Crops of pustules usually arise within a few hours on the typical-appearing palmar and plantar skin (Fig. 21-1). Involvement usually is symmetric but unilateral location on palms and/or soles is seen. Single lesions then become surrounded by an erythematous ring. Sometimes, the pustules extend to the dorsa of the fingers, the feet, or over the volar wrists (see Fig. 21-1C). Episodes of new pustular eruptions occur at varying intervals and remain strictly confined to the sites of predilection. As pustules become older, their yellow color changes to dark brown, so that in untreated PPP, the lesions show various shades of color (see Fig. 21-1C and D). Dried pustules are shed within approximately 8 to 10 days. There are no symptoms other than 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. As remission begins, fewer pustules are produced, but the skin may remain erythematous and hyperkeratotic, resembling eczema. Remissions last for days, weeks, or months until pustulation again occurs.

m C> CD a

CO

INFLAMMATORYDISORDERSBASEDONT-CELLREACTIVITYANDDYSREGULATION 216

FIGURE 211 Palmoplantar pustulosis. A and B. Groups of pustules measuring 2 to 3 mm in

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Disease Associations
An association of PPP and osteoarthritis of the anterior chest wall was first described in Japan." As reported by Swedish authors, involvement of the manubriosternal joint is present in 6 percent and of the sternoclavicular joints in 10 percent of patients." Scintigraphic investigations showed sternocostoclavicular joint involvement to be present in 16 of 78 (22 percent) patients." For this condition, the term SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) has been established.' Clinical manifestations of SAPHO syndrome are similar whether they occur in relation to severe acne (mostly acne conglobata) or PPP (see Chap. 78). The primary lesion consists of a sterile abscess containing neutrophils. The site of predilection is the anterior chest wall. SAPHO syndrome can be associated with pseudoinfectious arthritis. Involvement of the sacroiliacal joints may be present" PPP is also seen in patients with chronic recurrent multifocal osteomyeli-

diameter occur on erythematous skin on palms and soles. Both feet and both hands are normally affected symmetrically. C and D. Lesions may occasionally spread beyond the predilection sites, and pustules may appear on the wrists. 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.

tis as well as with noninfectious inflammatory bone lesions.

Histopathobgy
Histologically, there is an intraepidermal cavity filled with polymorphonuclear leukocytes associated with spongi form changes within the surrounding epidermis (Fig. 21-2). Eosinophils and mast cells are present in increased numbers in PPP biopsies from lesions] skin. Another hallmark is the inability to visualize the epidermal part of the eccrine duct in PPP specimens indicating an involvement of the acrosyringium.21

other laboratory tests are usually normal. In patients with an infectious trigger, infection-associated laboratory parameters, such as C-reactive protein, may be increased. Increased levels of anti-gliadin antibodies may occasionally be found.

Laboratory Findings
The lesions of PPP are sterile; a moderately increased white blood cell count may occasionally be observed, but all

FIGURE 212 Histologically, there is a spon-

gifonn pustule and a moderate lymphohistiocytic infiltrate.

Box 21-1 Differential Diagnosis

Treatment
PPP is difficult to treat and all reported treatments have a high recurrence rate. The management of PPP is summarized in Box 21-2. The first measure in the management of PPP is cessation of smoking. In patients with proven gluten intolerance, a glutenfree diet was found to have a beneficial effect on lesions in psoriasis and PPP.24 Among topical treatments only a few procedures have been identified as being of therapeutic benefit.25 Unilateral involvement and/or PPP with a limited effect on daily living activities should be treated with topical agents. Due to the fact that skin penetration through palmar and plantar skin is highly restricted even in acute disease with focal skin barrier disruption only certain drugs can be used effectively. Potent and superpotent steroids are the drugs of choice and may be used under plastic film or hydrocolloid occlusion, particularly in the beginning of therapy. Subsequent topical therapy with vitamin Ds-analogues such as calcipotriol/ calcipotriene, tazarotene, or anthralin may prevent a quick relapse in some patients. However, every prolonged topical steroid use is usually needed to maintain a therapeutic effect, particularly when combined with these compounds on an every second- or third-day basis; this may also delay cutaneous side effects. Psoralen and ultraviolet A light (PUVA) treatment has been used alone or in combination with systemic retinoids and found to be effective. PUVA bath or PUVA with application of the photosensitizer in an ointment or gel formulation showed beneficial effects in case-controlled studies.26 In disabling PPP and in PPP with a high frequency of relapse systemic therapy is preferred. A systematic review found retinoids to be the only drugs with proven

Most Likely Dyshidrotic eczema with secondary bacterial infection Tinea of palms and soles with pustules Consider
Keratoderma blenorrhagicum in Reiter disease Involvement of palms and soles in generalized pustular psoriasis Infected scabies with pustulation Vesicopustular mycosis fungoides of palms and soles Pustular localized vasculitis

efficacy. However, as there is a female preponderance in PPP, the use of systemic tabloids is restricted at least in women with childbearing potential. Other systemic agents with efficacy are methotrexate (10 to 25 mg/week) and cyclosporine. It has been shown that cyclosporine is effective in a low-dose regimen (1 to 2 mg/ kg/day) over a 1-year period?? Systemic steroids are of questionable value. Withdrawal is usually followed by a rebound. Efficacy of fumaric acid ester therapy in PPP has been decribed?8 There is debate as to whether TNF-a antagonists may be beneficial in PPP. Whereas in chronic plaque type psoriasis and generalized pustular psoriasis the anti-TIN a monoclonal antibody infliximab was found to be highly effective, this agent was found to be both of beneficial effect and to worsen PPP.2350 In the SAPHO syndrome, infliximab led to a complete remission of osteoarticular disease but PPP deteriorated during treatments' Efalizumab, an anti-CD11a monoclonal antibody, seems to be beneficial in PPP, but experience is limited.

Diagnosis and Differential Diagnosis (Box 21-1)

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 (see Chap. 16). 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. Rare clinical variants such as vesicopustular mycosis fungoides palmaris et plantaris,22 pustular localized vasculitis,23 or palmoplantar involvement of generalized pustular psoriasis may also resemble PPP.

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S E L O DS N SA M L A FP SO N O I T P U R RE A L U T S U P

ACRODERMATITIS CONTINUA (HALLOPEAU)

Acrodermatitis continua is a rare, sterile, pustular eruption of the fingers or toes that slowly extends proximally. Continuous pustulation leads to nail destruction and atrophy of the distal phalanx. In 1888, Crocket32 described a relapsing bullous and pustular eruption on hands and feet; this was further delineated by Hallopeau.33 Acrodermatitis continua is now classified as a form of acropustular psoriasis.

Clinical Features
Acrodermatitis continua most often begins at the tips of one or two fingers (Fig.

Box 21-2 Treatments for Palmoplantar Pustubsis and Acrodermatitis Continua First line TOPICAL Potent and superpotent steroids Calcipotrid Anthralin Tazarotene bid, plastic film occlusion bid Once daily bid PHYSICAL Bath-psoralen and ultraviolet light 4Mk SYSTEMIC Acitretin 0.5 mg/kg/bw/day 10-25 mg/wk 3-5 mg/kg/bw, when effective individual titration of dose According to dose-escalation scheme, corresponding to a maximum of 720 mg of dimethylfumarate/day 1 mg/kg/bw/wk

Seco nd line

Methotrexate Cyclosporine Fumaric acid estersa Efalizumab

Third 'Registered in Germany only. line

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