| Generalized pustular psoriasis | |
|---|---|
| Specialty | Dermatology  |
Generalized pustular psoriasis (GPP) is a rare type of psoriasis that can present in a variety of forms. [1] Unlike the most general and common forms of psoriasis, GPP usually covers the entire body and with pus-filled blisters rather than plaques. GPP can present at any age, but is rarer in young children. It can appear with or without previous psoriasis conditions or history, and can reoccur in periodic episodes.
GPP presents as pustules and plaques over a wide area of the body. It differs from the localized form of pustular psoriasis in that patients are often febrile and systemically ill. [2]
However, the most prominent symptom, as described in the Archives of Dermatology, is "sheeted, pinhead-sized, sterile, sub-corneal pustules". [3] The IPC roundtable adds that these pustules often occur either at the edges "of expanding, intensely inflammatory plaques" or "within erythrodermic skin". [4]
Most cases of generalized pustular psoriasis present in patients with existing or prior psoriasis conditions. [3] [4] However, there are many cases of GPP that arise without a history of psoriasis. [4]
The Department of Dermatology of the University of São Paulo proposed a classification for these two conditions. Pso+ represents patients with a personal history of psoriasis and pso- represents patients with no history of psoriasis. They also identified a common factor among patients in each group: In the pso+ group, the most common precipitating factor is corticosteroid withdrawal. In the pso- group, the most common precipitating factor is infection. [5]
In a large portion of cases, the disease is brought on by some triggering factor. Through research and observation, many of these factors have been identified. The following table, from an article in Cutis, lists a few factors that have been observed as influential in the onset of GPP.
| Provocative Factors Influencing Pustular Psoriasis |
|---|
| Drugs: lithium, aspirin, salicylates, methotrexate, corticosteroids, progesterone, phenylbutazone, trazodone, penicillin, hydroxychloroquine |
| Irritation from topical therapy: coal tar, anthralin |
| Infections: dental, upper respiratory |
| Pregnancy |
| Solar irradiation |
Source: "Table II", "Pustular Psoriasis" Farber and Nall, 1993 [6]
Although there are likely to be multiple genetic factors and environmental triggers, mutations causing defects in the IL-36RN, CARD14 and AP1S3 genes have been shown to cause GPP. [7] [8] [9]
It is important to note that while there are different forms of GPP, they are not exclusive of each other. One can morph into another, or multiple forms can occur simultaneously. [2]
Von Zumbusch psoriasis is named after the German dermatologist Leo Ritter von Zumbusch (1874–1940), son of Kaspar von Zumbusch, who described the first documented case of generalized pustular psoriasis in the early 1900s. See Case Report #1. Sometimes all or any of GPP is referred to as von Zumbusch psoriasis, but in the literature it is often distinguished as one specific form of GPP. [2] [6]
Eugene M. Farber, MD and colleagues provide a description of von Zumbusch psoriasis in "Pustular Psoriasis", published in Cutis. They describe the pattern as having "waves of widespread or universally fiery redness". The affected areas are "painful and tender". Small sub-corneal pustules form, with sizes originally between 1 and 10 mm in diameter. These pustules may merge to form "yellow-green lakes of pus". The pustules dry out, and "Waves of scarlatiniform [resembling scarlet fever] peeling follow, removing the desiccating pustules". In regards to the onset, the von Zumbusch form may "supervene on any previous pattern of psoriasis". It also may or may not recur periodically. [6]
This form of GPP tends to have symmetrical and grouped features. It usually onsets early in the third trimester of pregnancy, and generally persists until the child is born, but occasionally long after.
In 2009, Dr. Debeeka Hazarika, president of the North East States branch of the Indian Association of Dermatologists, Venereologists and Leprologists (IADVL), published an article titled "Generalized pustular psoriasis of pregnancy successfully treated with cyclosporine" in Indian J Dermatol Venereol Leprol. As reported by Hazarika, there have been up to nine instances where the disease was recurrent in subsequent pregnancies. [10] See Case Report 2
In 1979, Frank R. Murphy, MD and Lewis P. Stolman, MD reported on the case of a woman who developed generalized pustular psoriasis in response to doses of progestins, suggesting a link between progestogens and GPP. Most cases of GPP in pregnancy occur late in the third trimester, generally when production of progesterone increases. [2]
GPP is a rare disease in general, but even more so in children. In 2010, an article was published in Pediatric Dermatology by the Department of Dermatology, University of São Paulo. The report acknowledged that psoriasis is a relatively common skin condition in children, but "the pustular variant is rare." Out of 1,262 cases of psoriasis in children, a "0.6% rate of pustular variants" was found. [5] When GPP does occur in children, it usually appears during the first year of life. [11]
Khan et al. reported that in GPP patients ten or younger, less than 12% of cases are preceded by ordinary psoriasis. This differs greatly from GPP cases in adults, where 85% of GPP is preceded by typical psoriatic lesions. [3]
According to the article by the University of São Paulo, mentioned above, "The onset of childhood GPP is generally abrupt and accompanied by toxic features." The original acute episode usually lasts a few days, but "repeated waves of inflammation and pustulation may follow." It is important that the disease is managed immediately in order to prevent life-threatening complications, such as infection or [sepsis]. Other complications include "metabolical, hemo-dynamic, and thermoregulatory disturbances" which occur as a result of "alterations of the epidermal barrier." [5]
See Case Report 3
This type of psoriasis appears as round lesions. It begins as discrete areas that become raised and swollen. Pustules appear at the edges of the round lesions, creating rings. The pustules then dry out and leave a trail of scale as the lesion grows. [6]
See Case Report 4
Treatments vary widely, and many different drugs have been documented as being successful. Some medications are successful in some patients, while unsuccessful in others. Below is a list of some medications used to treat GPP: [6] [10] [11] [12] [13]
GPP is a rare and severe type of psoriasis. It in rare cases it is said to be fatal and in some cases has driven patients to intensive burn units. [14] An article published in Pediatric Dermatology said, "The GPP pattern is as an acute, episodic, and potentially life-threatening form of psoriasis." [5] There is no cure-all treatment for GPP, and as such, the mortality rate is high. Ryan and Baker study from 1971 observed 155 patients with GPP, 106 of which were followed up with. 26 of those 106 died as a result of the psoriasis or the treatment. [15] Their data gives a 25% mortality rate.
Von Zumbusch observed a male patient, who had had classic psoriasis for several years, and who then went through recurrent episodes of bright [erythema] and [edema], which became studded with multiple pustules. Von Zumbusch observed this patient through nine hospital admissions over 10 years. [3] [13]
Hazarika gave a report of a 29-year-old woman with no family history of psoriasis, having had a normal first pregnancy, who presented with GPP in the twenty-eighth week of her second pregnancy. Steroid therapy caused a worsening of the symptoms. With cyclosporine the lesions cleared in 10–14 days, but new lesions appeared. The patient gave birth to a healthy baby in the thirty-eighth week of pregnancy. A month and a half after delivery, the woman presented with a psoriatic plaque on her leg. [10]
An eleven-year-old boy had an eight-year history of recurrent GPP. He suffered from "fever, malaise and pain". He was treated with acitretin, and improvement was seen in five weeks. [13]
In 1991, a case was reported of a man having plaque psoriasis and treating it with UV radiation at a tanning salon. After receiving a partial thickness burn from overexposure, he presented with annular pustular psoriasis, which cleared after 21 days, only to reoccur every 3 to 6 weeks for a year. [16]
A case report published in the Journal of Dermatological Treatment documents the successful use of adalimumab to control symptoms and induce relapse for 72 weeks. "Adalimumab is ... approved for the treatment of moderate to severe rheumatoid arthritis ... and more recently for the treatment of psoriatic arthritis". [12]
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon.
Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. This often happens in association with changes to the nails such as small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. Skin changes consistent with psoriasis frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy.
A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.
Papular mucinosis is a rare skin disease. Localized and disseminated cases are called papular mucinosis or lichen myxedematosus while generalized, confluent papular forms with sclerosis are called scleromyxedema. Frequently, all three forms are regarded as papular mucinosis. However, some authors restrict it to only mild cases. Another form, acral persistent papular mucinosis is regarded as a separate entity.
Heinrich Koebner ; was a German-Jewish dermatologist born in Breslau.
Psoriasis Area and Severity Index (PASI) is the most widely used tool for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 to 72.
The term pustular psoriasis is used for a heterogeneous group of diseases that share pustular skin characteristics.
Pruritic folliculitis of pregnancy is a skin condition that occurs in one in 3000 people, about 0.2% of cases, who are in their second to third trimester of pregnancy where the hair follicle becomes inflamed or infected, resulting in a pus filled bump. Some dermatologic conditions aside from pruritic folliculitis during pregnancy include "pruritic urticarial papules and plaques of pregnancy, atopic eruption of pregnancy, pemphigoid gestationis, intrahepatic cholestasis of pregnancy, and pustular psoriasis of pregnancy". This pruritic folliculitis of pregnancy differs from typical pruritic folliculitis; in pregnancy, it is characterized by sterile hair follicles becoming inflamed mainly involving the trunk, contrasting how typical pruritic folliculitis is mainly localized on "the upper back, shoulders, and chest." This condition was first observed after some pregnant individuals showed signs of folliculitis that were different than seen before. The inflammation was thought to be caused by hormonal imbalance, infection from bacteria, fungi, viruses or even an ingrown hair. However, there is no known definitive cause as of yet. These bumps usually begin on the belly and then spread to upper regions of the body as well as the thighs.
Impetigo herpetiformis is a form of severe pustular psoriasis occurring in pregnancy which may occur during any trimester.
Erosive pustular dermatitis of the scalp presents with pustules, erosions, and crusts on the scalp of primarily older Caucasian females, and on biopsy, has a lymphoplasmacytic infiltrate with or without foreign body giant cells and pilosebaceous atrophy.
Psoriatic erythroderma represents a form of psoriasis that affects all body sites, including the face, hands, feet, nails, trunk, and extremities. This specific form of psoriasis affects 3 percent of persons diagnosed with psoriasis. First-line treatments for psoriatic erythroderma include immunosuppressive medications such as methotrexate, acitretin, or ciclosporin.
Acute generalized exanthematous pustulosis is a rare skin reaction that in 90% of cases is related to medication.
Inflammatory Linear Verrucous Epidermal Nevus is a rare disease of the skin that presents as multiple, discrete, red papules that tend to coalesce into linear plaques that follow the Lines of Blaschko. The plaques can be slightly warty (psoriaform) or scaly (eczema-like). ILVEN is caused by somatic mutations that result in genetic mosaicism. There is no cure, but different medical treatments can alleviate the symptoms.
Apremilast, sold under the brand name Otezla among others, is a medication for the treatment of certain types of psoriasis and psoriatic arthritis. The drug acts as a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It is taken by mouth.
Stasis papillomatosis is a disease characterized by chronic congestion of the extremities, with blood circulation interrupted in a specific area of the body. A consequence of this congestion and inflammation is long-term lymphatic obstruction (lymphedema). It is also typically characterized by the appearance of numerous papules. Injuries can range from small to large plates composed of brown or pink, smooth or hyperkeratotic papules. The most typical areas where injuries occur are the back of the feet, the toes, the legs, and the area around a venous ulcer formed in the extremities, although the latter is the rarest of all. These injuries include pachydermia, lymphedema, lymphomastic verrucosis and elephantosis verrucosa. The disease can be either localized or generalized; the localized form makes up 78% of cases. Treatment includes surgical and pharmaceutical intervention; indications for partial removal include advanced fibrotic lymphedema and elephantiasis. Despite the existence of these treatments, chronic venous edema, which is a derivation of stasis papillomatosis, is only partially reversible. The skin is also affected and its partial removal may mean that the skin and the subcutaneous tissue are excised. A side effect of the procedure is the destruction of existing cutaneous lymphatic vessels. It also risks papillomatosis, skin necrosis and edema exacerbation.
Calcipotriol/betamethasone dipropionate, sold under the brand name Taclonex among others, is a fixed-dose combination medication of the synthetic vitamin D3 analog calcipotriol (also known as calcipotriene) and the synthetic corticosteroid betamethasone dipropionate for the treatment of plaque psoriasis. It is used in the form of ointment, topical suspension, gel, aerosol, and foam.
Risankizumab, sold under the brand name Skyrizi, is a humanized monoclonal antibody used for the treatment of plaque psoriasis, psoriatic arthritis, and Crohn's disease. It is designed to target interleukin 23A (IL-23A). It is given by subcutaneous injection.
Von Zumbusch (acute) generalized pustular psoriasis is the most severe form of generalized pustular psoriasis, and can be associated with life-threatening complications.
Spesolimab, sold under the brand name Spevigo, is a monoclonal antibody used for the treatment of generalized pustular psoriasis (GPP). It is an interleukin-36 receptor (IL-36R) antagonist. It is given via injection into a vein.
Joel M. Gelfand is an American dermatologist and epidemiologist at the University of Pennsylvania in Philadelphia, Pennsylvania. He currently serves as the James J. Leyden Professor in Clinical Investigation, the Vice Chair of Clinical Research, the director of the Psoriasis and Phototherapy Treatment Center, and the medical director of the Clinical Studies Unit in the Department of Dermatology at the Perelman School of Medicine at the University of Pennsylvania. He studies systemic comorbidities of psoriasis and much of his research has centered on the connection between cardiovascular disease and psoriasis.