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Palmoplantar Pustulosis

PPP

Palmoplantar pustulosis (PPP) is a chronic relapsing disorder associated with recurring crops of sterile pustules on palms and soles. Palmoplantar pustulation is frequently accompanied by the formation of erythematous desquamative plaques, which complicate the differentiation of PPP and palmoplantar psoriasis, a variant of plaque psoriasis. The diagnosis of PPP thus rests on histological studies. Considerable knowledge gaps regarding the etiology and pathogenesis of PPP hinder the development of effective therapies. Most patients receive immunosuppressive treatments or phototherapy, which may relieve their complaints, but long-term results are far from satisfying.


Presentation

Dermatological findings characteristic of PPP comprise yellow pustules on palms and/or soles, that measure up to 10 mm in diameter, are well demarcated but tend to coalesce. These pustules erupt and resolve with brownish discoloration, and due to the relapsing course of PPP, brown macules developed during prior episodes are frequently observed adjacent to new pustules. During acute episodes, erythema may be noted on affected areas of palms and soles [1]. Patients often claim burning sensations and itching [2]. Hyperkeratosis and scaling may be seen. In the long term, painful cracks and fissures may form [2]. While asymmetry is not an exclusion criterion, lesions often develop symmetrically [1].

As per definition, PPP-related skin lesions are limited to the palms and soles. Nevertheless, nail involvement is reported in about 10% of cases. Subungal pustulation may be associated with superficial anomalies like pitting and may eventually lead to onycholysis [3]. Because PPP patients tend to present symptoms resulting from concomitant psoriasis, it may be difficult to clarify whether this finding is related to one disease or the other [1] [4]. In the absence of extrapalmoplantar skin lesions, nail involvement is usually attributed to PPP [3]. By contrast, erythematous desquamative plaques that extend beyond the limits of palms and soles are rather suggestive of plaque psoriasis, even in case of palmoplantar predominance, and plaque psoriasis is commonly associated with nail changes [5].

Pain
  • Each pain score improved statistically significantly at the indicated times after the initiation of treatment (P 0.05). The QoL score improved significantly with a good correlation with the relevant pain scores.[ncbi.nlm.nih.gov]
  • Abstract A 46-year-old man who had been suffering from palmoplantar pustulosis (PPP) for 3 years had anterior chest pain and left temporal pain from six months after the onset of his disease.[ncbi.nlm.nih.gov]
  • In addition to skin lesions, PPP patients may present with severe joint pain and pustulotic arthro-osteitis (PAO), especially of the sternoclavicular joint.[ncbi.nlm.nih.gov]
  • Clinical efficacy was assessed on a 0-4 point scale for erythema, desquamation, infiltration, and pustulation, and on a 0-3 point pain scale.[ncbi.nlm.nih.gov]
  • Palmoplanar pustules may rarely be associated with chronic recurrent multifocal osteomyelitis in children and young adults, Additional features of this disorder are recurrent low-grade fevers and bone pain.[scholars.northwestern.edu]
Difficulty Walking
  • The most common complications include: difficulty walking or doing daily tasks pain that affects activities and sleep infection from scratching your itchy palms and soles It may not be possible to prevent all cases of palmoplantar pustulosis.[healthline.com]
Burning Pain
  • It is characterized by sudden appearance of erythema – an inflammation which feels hot when you touch it, causing burning pain. After a while vesicles appear on psoriatic foci, transforming the latter to psoriatic pustules.[noskinproblems.com]
High Fever
  • Abstract A 64-year-old man with a 10-year history of palmoplantar pustulosis, a recent history of cranial surgery and a persistent upper airway infection presented with a high fever and deep coma.[ncbi.nlm.nih.gov]
Sternoclavicular Joint Pain
  • After administration of cefcapene pivoxil hydrochloride (CFPN-PI), a third-generation cephalosporin, the swelling and sternoclavicular joint pain were promptly reduced and dramatically improved in all 3 cases.[ncbi.nlm.nih.gov]
Eruptions
  • We observed significant reduction in the frequency of pustular eruptions and the number of pustules with maximum tolerable doses of colchicine treatment for up to 12 months.[ncbi.nlm.nih.gov]
  • KEYWORDS: Erythema; Granulocyte and monocyte adsorption apheresis; Palmoplantar pustulosis; Pustules; Skin eruptions [Indexed for MEDLINE] Free full text[ncbi.nlm.nih.gov]
  • Hallopeau disease - a sterile pustular eruption of the fingers and toes. Synonym(s): pemphigus vegetans ; pustulosis palmaris et plantaris Hallopeau-Siemens syndrome[medical-dictionary.thefreedictionary.com]
  • Palmoplantar pustulosis is characterized by a chronic eruption of sterile pustules on palms and soles. The disease affects mainly women in the sixth and seventh decade of life.[ncbi.nlm.nih.gov]
  • Pustulosis palmaris et plantaris or palmoplantar pustulosis (PPP) is a refractory pustular eruption of the palms and soles with unknown etiology.[ncbi.nlm.nih.gov]
Erythema
  • Abstract Palmoplantar pustulosis (PPP) is characterized by neutrophilic pustules with erythema, which are limited to the hands and feet.[ncbi.nlm.nih.gov]
  • Three of six patients showed complete clearance of pustules, significant reduction of erythema, and unnoticeable desquamation, whereas the other three patients had no new pustules appearing and had modest reduction of erythema and desquamation.[ncbi.nlm.nih.gov]
  • Clinical efficacy was assessed on a 0-4 point scale for erythema, desquamation, infiltration, and pustulation, and on a 0-3 point pain scale.[ncbi.nlm.nih.gov]
  • RESULTS: The improvement in the symptom (erythema, pustules/vesicles, hyperkeratosis/scales) scores was high for the combination therapy.[ncbi.nlm.nih.gov]
  • The patient developed palmoplantar pustulosis characterized by redness, pustules, vesicles, and scaly erythema on his hands and feet 1 month after obtaining cobalt chromium alloy cast crowns on his molar teeth. The symptoms persisted for 1 year.[ncbi.nlm.nih.gov]
Blister
  • Your doctor will examine the skin on your palms and soles to check for blisters or pustules. They may need to do several tests to rule out other medical problems.[healthline.com]
  • Typically, an infant develops small flat red areas on the palms and soles which become raised, develop into tiny blisters, then pustules , which heal with small temporary pigmented areas. The lesions are itchy.[dermnetnz.org]
  • HFMD also produces blisters on the palms and soles. But unlike acropustulosis, HFMD usually begins with a fever and sore throat. There may be sores in the mouth and elsewhere on the body with HFMD too.[healthline.com]
  • Pathologically, PPP pustules aresubcorneal blisters, containing polymorphonuclear leukocyte infiltrations.[jle.com]
  • Imagine not being able to walk because of painful blisters on your feet, one of the symptoms of pustular.[rykunuxucyga.y0.pl]
Pruritus
  • The adverse effects were limited including burning sensation, pruritus, and hyperpigmentation. UVA1 is an effective therapy for PPP with mild side effects.[ncbi.nlm.nih.gov]
  • Abstract Palmoplantar pustulosis (PPP) is a chronic pustular dermatitis of the palms and soles, which is frequently associated with significant pruritus and pain, often limiting daily activities.[ncbi.nlm.nih.gov]
  • Affected individuals may also experience itching (pruritus), pain, or a burning sensation. [1] [2] [3] The classification of PPP is controversial.[rarediseases.info.nih.gov]
  • This point may need to be emphasised to the family: aside from the pruritus being unpleasant, this condition has no particular consequences. N.B. : This limited content is for the general public.[therapeutique-dermatologique.org]
  • Family members should also be questioned and examined for pruritus and burrows. Eosinophilic folliculitis occurs mainly on the scalp rather than the hands and feet but may cycle concurrently with AI.[visualdx.com]
Dry Skin
  • Things that make them worse include Infections Stress Dry skin Certain medicines Psoriasis usually occurs in adults. It sometimes runs in families. Treatments include creams, medicines, and light therapy.[icdlist.com]
  • General suggestions include s moking cessation and emollients (non-cosmetic moisturizers) to soften dry skin and prevent cracking.[rarediseases.info.nih.gov]
  • Emollients Use plenty of grease or other thick emollient to soften the dry skin to prevent fissures . Soak in warm water with emulsifying ointment for 10 minutes.[dermnetnz.org]
  • Systemic drugs are indicated in its severe form, but side effects.Palmoplantar pustulosis (PPP) callouses, dry skin or cuts. These can be painful depending on where they occur.[jabuxutih.xpg.com.br]

Workup

In the presence of psoriatic skin lesions outside the palmoplantar region, the differentiation of PPP and psoriasis may pose a major challenge. Indeed, it may not be possible to clinically distinguish PPP from palmoplantar psoriasis in these cases [4]. Otherwise, PPP is diagnosed clinically.

In case of doubts, histological studies may be carried out to support the tentative diagnosis of PPP. Tissue samples are obtained by skin biopsy, and their microscopic examination reveals the neutrophilic infiltration of the acrosyringium of sweat glands [5]. The spiral architecture of these eccrine ducts may be lost [6]. Acanthosis and parakeratosis may be observed but don't usually dominate the image. PPP-related pustules are sterile lesions, which is reflected in histological and microbiological findings [5].

HLA-B8
  • Abstract We examined granulocytes or polymorphonuclear leukocytes (PMN) in an HLA B8 patient with palmoplantar pustulosis (PPP). Controls included another patient with PPP, however, lacking this antigen and a healthy, HLA B8 person.[ncbi.nlm.nih.gov]

Treatment

Because the etiology and pathogenesis of PPP remain poorly understood, causal treatment is not available. In the majority of cases, corticosteroids are applied on affected areas. The thicker stratum corneum of palms and soles diminishes the efficacy of topically delivered agents, so they are generally applied under hydrocolloid dressing occlusion. Corticosteroids may be combined with retinoids to potentiate the efficacy of the former and to minimize the risk of side effects [7]. If topical medication doesn't yield the desired effect, immunosuppressive and/or anti-inflammatory drugs may be administered systemically. Acitretin and methotrexate are most commonly prescribed to this end [8]. Regardless of the decision for topical or systemic medication, continued treatment is often required after achieving remission to avoid the recurrence of pustulation [6]. Phototherapy constitutes a valuable alternative to the immunosuppressive approach. Oral psoralen plus irradiation with ultraviolet light A alleviates symptoms in the majority of patients, but recurrence is equally likely upon the cessation of therapy [6] [7].

Either of the aforementioned therapeutic approaches has been reported to induce complete or partial responses but has proven ineffective in other instances, which highlights the need for new PPP treatments [2] [5]. Current research is focused on countering disturbances of the immune system, e.g., by antagonizing IL-17. Secukinumab and ixekizumab are monoclonal antibodies against IL-17 whose safety and efficacy in PPP management have been tested in clinical trials. The results of these trials are highly promising [5]. At the same time, other targets of PPP immunotherapy are studied: Inhibitors of phosphodiesterase-4 gained the attention of scientists, and apremilast has successfully been used to treat PPP [9]. Apremilast has been shown to inhibit numerous T-cell-derived cytokines, including but not limited to IL-17, interferon-γ, and tumor necrosis factor-α [9] [10]. Although tumor necrosis factor antagonists have been implicated in the pathogenesis of the disease [11], infliximab, a monoclonal antibody against tumor necrosis factor-α, has proven effective in PPP therapy [12].

Prognosis

PPP is a painful and sometimes disabling condition with a significant impact on the patient's quality of life. During severe episodes, PPP patients may not be able to use their hands or walk [1]. The disease has a chronic course with intermittent flares mostly followed by partial, rarely by complete remissions [2]. The mean duration of PPP is 7 years, but some patients suffer for decades [1]. Current knowledge regarding the causes and course of the disease does not allow for a prediction of disease duration in individual cases.

Etiology

The triggers of PPP remain unknown. Smoking, an increased physical, emotional, or psychological burden due to infectious diseases, stress, and anxiety, as well as immunomodulators like tumor necrosis factor antagonists, have been linked to the development of PPP and the aggravation of episodes [1] [11]. Furthermore, PPP has been associated with systemic disorders like diabetes mellitus type 2, autoimmune thyroid disease, celiac disease, and SAPHO syndrome [1] [5]. These observations may suggest an immunological component in PPP pathogenesis. Indeed, molecular biological studies revealed an overexpression of IL-17 in palms and soles of PPP patients [13].

PPP has also been related to missense mutations in the CARD14 gene, which encodes for caspase recruitment domain family member 14, a protein that is involved in cellular adhesion and proinflammatory signaling [14]. By contrast, European and Asian studies argue against an involvement of the IL36RN gene in the pathogenesis of PPP [14] [15]. Both mutations of CARD14 and IL36RN have been detected in patients suffering from plaque psoriasis, so there is an overlap of genetic susceptibility, but there are differences, too. These differences may account for the characteristic distribution of pustular lesions in PPP patients, and they may possibly explain treatment success and failure.

Epidemiology

PPP is a chronic disorder that may affect patients of any age, gender, and ethnicity. The disease is diagnosed at a mean age of 45 years, but it has also been reported in children and adults of very old age [1]. The majority of affected individuals is female [1] [8]. In Japan, the prevalence of PPP has been estimated to 0.12% [16].

Sex distribution
Age distribution

Pathophysiology

PPP-related vesicles form in the upper coiled ducts of eccrine sweat glands, i.e., in the acrosyringium [4]. Histologically, these vesicles impress by the infiltration of neutrophils, which are surrounded by lymphocytes that have been shown to produce IL-6, IL-17, interferon-γ, and tumor necrosis factor-α. Distinct hypotheses have been postulated to explain this condition [5]:

On the one hand, smoking is associated with nicotine excretion via the sweat glands, and nicotine may alter the reaction of immune cells in the acrosyringium. Smoking has also been related to the generation of autoantibodies against nicotinic acetylcholine receptors. Such antibodies have been found to bind to epitopes in the palmar sweat glands [17].

On the other hand, the aforementioned lymphocytes may derive from memory effector cells that have been generated in the context of tonsillitis or upper respiratory infections. But even though evidence has been provided that such effector cells may home to the skin [18], the question of the disease' limitation to the palmoplantar region remains unanswered. Regardless of the latter, the hypothesis is supported by a Japanese metastudy describing the exacerbation of PPP upon acute tonsillitis, and marked improvement or complete remission of PP after tonsillectomy [19]. These processes may be favored by a genetic predisposition of the PPP patient.

Prevention

Few recommendations can be given to prevent PPP or to avoid episodes of renewed pustulation. Certain lifestyle decisions may be helpful to lower the individual risk of developing PPP, such as the decision to refrain from smoking. However, it remains unclear whether the cessation of smoking after the onset of symptoms affects the course of the disease [2]. In general, PPP patients may benefit from measures to prevent infectious diseases and to reduce their overall burden of stress, but evidence has not yet been provided to this end. In the few cases where PPP can clearly be attributed to the administration of determined drugs, namely inhibitors of tumor necrosis factor-α, the feasibility of switching to an alternative agent should be ascertained [11].

Summary

PPP is a chronic skin disease that is limited to the palms and soles. For a long time, it has been considered a localized pustular variant of psoriasis. This changed in 2007, when PPP was re-classified as a separate entity [5]. Nevertheless, the classification of PPP remains an issue of ongoing debate. The high incidence of psoriasis among PPP patients - about one-third of those suffering from PPP present psoriasis-related symptoms - suggests an etiological association between these two conditions [4] [8].

In general, the etiology remains poorly understood. A variety of genetic and environmental factors has been discussed in this context, but the specific triggers of symptom onset and flare-ups have not yet been identified. Accordingly, it is not yet possible to predict acute episodes, exacerbations, and the long-term course of the disease.

Most patients receive topical or systemic immunosuppressive treatment or phototherapy, but symptoms often recur after the discontinuation of therapy [5] [6]. Prolonged treatments, however, are associated with considerable side effects, so an acceptable compromise between the latter and PPP-related disability has to be sought [9]. Spontaneous remission may occur after prolonged periods of time, possibly after decades, but has also been reported after a brief period of severe illness.

Patient Information

Palmoplantar pustulosis (PPP) is a chronic skin disease of as-of-yet unknown cause. PPP patients suffer from episodic pustulations involving their palms and/or soles. Numerous yellow pustules form in affected areas, erupt and resolve with brownish decoloration. Flare-ups may be associated with burning and itching, and are generally painful. They may hinder the patients to use their hands or to walk. In the long term, affected individuals may note an exuberant cornification and scaling, and fissures and cracks may appear. A minor portion of patients presents with nail changes, but PPP-related pustules don't usually form outside the palmoplantar region. This is important to note because the distribution of skin lesions allows for the differentiation of PPP and plaque psoriasis. Nevertheless, doubts may remain regarding the distinction of PPP from an equally limited variant of plaque psoriasis. If a clinical diagnosis is deemed unfeasible, the dermatologist may opt for a skin biopsy. This way, tissue samples can be obtained for histological studies.

There are different ways to treat PPP. Unfortunately, though, causal therapies are not available, and the cure of PPP cannot be achieved in all cases. The most common approach to PPP treatment involves the topical application of corticosteroids. If it doesn't yield the desired results, immunosuppressive and anti-inflammatory agents may be administered systemically. Phototherapy constitutes an alternative to immunosuppression. While all these therapies may alleviate symptoms, recurrence is likely after the cessation of treatment. Its continuation may, however, have considerable side effects. An acceptable compromise needs to be found that considers the response of the individual patient.

Complete remission has been achieved by drug therapy or spontaneously, but it is not currently possible to predict exacerbations and remissions or the long-term outcome of the disease.

References

Article

  1. Olazagasti JM, Ma JE, Wetter DA. Clinical Features, Etiologic Factors, Associated Disorders, and Treatment of Palmoplantar Pustulosis: The Mayo Clinic Experience, 1996-2013. Mayo Clin Proc. 2017; 92(9):1351-1358.
  2. Marsland AM, Chalmers RJ, Hollis S, Leonardi-Bee J, Griffiths CE. Interventions for chronic palmoplantar pustulosis. Cochrane Database Syst Rev. 2006; (1):Cd001433.
  3. Hiraiwa T, Yamamoto T. Nail involvement associated with palmoplantar pustulosis. Int J Dermatol. 2017; 56(2):e28-e29.
  4. Brunasso AMG, Massone C. Psoriasis and palmoplantar pustulosis: an endless debate? J Eur Acad Dermatol Venereol. 2017; 31(7):e335-e337.
  5. Raposo I, Torres T. Palmoplantar Psoriasis and Palmoplantar Pustulosis: Current Treatment and Future Prospects. Am J Clin Dermatol. 2016; 17(4):349-358.
  6. Naik HB, Cowen EW. Autoinflammatory pustular neutrophilic diseases. Dermatol Clin. 2013; 31(3):405-425.
  7. Adişen E, Gürer MA. Therapeutic options for palmoplantar pustulosis. Clin Exp Dermatol. 2010; 35(3):219-222.
  8. Wilsmann-Theis D, Jacobi A, Frambach Y, et al. Palmoplantar pustulosis - a cross-sectional analysis in Germany. Dermatol Online J. 2017; 23(4).
  9. Haebich G, Kalavala M. Successful treatment of refractory palmoplantar pustulosis with apremilast. Clin Exp Dermatol. 2017.
  10. Schafer PH, Parton A, Capone L, et al. Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. Cell Signal. 2014; 26(9):2016-2029.
  11. Shmidt E, Wetter DA, Ferguson SB, Pittelkow MR. Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-alpha inhibitors: the Mayo Clinic experience, 1998 to 2010. J Am Acad Dermatol. 2012; 67(5):e179-185.
  12. Sanchez IM, Sorenson E, Levin E, Liao W. The Efficacy of Biologic Therapy for the Management of Palmoplantar Psoriasis and Palmoplantar Pustulosis: A Systematic Review. Dermatol Ther (Heidelb). 2017; 7(4):425-446.
  13. Bissonnette R, Nigen S, Langley RG, et al. Increased expression of IL-17A and limited involvement of IL-23 in patients with palmo-plantar (PP) pustular psoriasis or PP pustulosis; results from a randomised controlled trial. J Eur Acad Dermatol Venereol. 2014; 28(10):1298-1305.
  14. Mössner R, Frambach Y, Wilsmann-Theis D, et al. Palmoplantar Pustular Psoriasis Is Associated with Missense Variants in CARD14, but Not with Loss-of-Function Mutations in IL36RN in European Patients. J Invest Dermatol. 2015; 135(10):2538-2541.
  15. Takahashi T, Fujimoto N, Kabuto M, Nakanishi T, Tanaka T. Mutation analysis of IL36RN gene in Japanese patients with palmoplantar pustulosis. J Dermatol. 2017; 44(1):80-83.
  16. Kubota K, Kamijima Y, Sato T, et al. Epidemiology of psoriasis and palmoplantar pustulosis: a nationwide study using the Japanese national claims database. BMJ Open. 2015; 5(1):e006450.
  17. Hagforsen E, Awder M, Lefvert AK, Nordlind K, Michaëlsson G. Palmoplantar pustulosis: an autoimmune disease precipitated by smoking? Acta Derm Venereol. 2002; 82(5):341-346.
  18. Nozawa H, Kishibe K, Takahara M, Harabuchi Y. Expression of cutaneous lymphocyte-associated antigen (CLA) in tonsillar T-cells and its induction by in vitro stimulation with alpha-streptococci in patients with pustulosis palmaris et plantaris (PPP). Clin Immunol. 2005; 116(1):42-53.
  19. Wu W, Debbaneh M, Moslehi H, Koo J, Liao W. Tonsillectomy as a treatment for psoriasis: a review. J Dermatolog Treat. 2014; 25(6):482-486.

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Last updated: 2018-06-26 06:21