Background: Guttate psoriasis (GP), a distinct variant of psoriasis, is more common in children and adolescents. The long-term course of these patients has sparsely been examined, with few studies reporting the rates of relapse, persistence, and further development of the psoriasis vulgaris phenotype. Objectives: The objective of this study was to characterize the long-term outcomes of new-onset GP and elucidate the potential factors associated with a persistent disease course. Methods: This was a retrospective cohort study. Patients diagnosed with new-onset GP between 2009 and 2020 with a follow-up period of at least 1 year, were enrolled. The examinees were evaluated by dermatologists. Detailed data retrieved from the examinees’ medical files included demographics, disease characteristics, treatment, and comorbidities. A structured telephone questionnaire was used to determine the current psoriasis status: type, severity, and extent. At the end of follow-up, patients with a persistent disease course, defined as having lesions at least a year after disease onset, were compared with patients in complete remission without further psoriasis symptoms. Results: A total of 120 patients (mean age 28.8 years [±15.2], 58.3% women) with new-onset GP flare were identified. At the end of follow-up period (mean 6.2 years [±3.1]), 49.1% (n = 59) of the patients reported active persistent psoriasis. A switch to the psoriasis vulgaris phenotype occurred in 17.5% (n = 21) of the study cohort. Persistent psoriasis was associated with male sex (OR = 2.1, p < 0.05), multiple disease flares (>3; OR = 9.1, p < 0.001), switch to the vulgaris phenotype (OR = 4.16, p < 0.001), and palmoplantar involvement (OR = 5.2, p < 0.01). Conclusion: A persistent disease course is common among patients with new-onset GP, with most retaining their guttate phenotype throughout the disease course. Persistency was associated with male sex, multiple GP flares, switching to the vulgaris phenotype, and palmoplantar involvement.

Guttate psoriasis (GP) is a variant of psoriasis that has distinct epidemiological, clinical, and histological characteristics. Unlike psoriasis vulgaris (PV), GP is more common in children and adolescents than in adults [1], it affects people of all races, as well as men and women [2]. GP manifests as several small (2–10 mm diameter) “drop-like” scaly plaques. As an immune-mediated disorder, its onset is typically 1–3 weeks following an acute infection, such as streptococcal tonsillitis [3‒5]. Immunohistochemical analysis of the tonsils and skin lesions in patients with GP demonstrated shared T-cell clones, suggesting that GP is caused by autoimmune cross-reactivity to streptococcal antigen [6]. Additional risk factors for GP include stressful life events and family history of psoriasis [7]. Prognosis is considered better than other types of psoriasis because of rapid involution even without treatment within a few weeks to months following its appearance [8].

Data evaluating the natural history of GP are scarce, particularly the question of long-term outcomes. The reported rates of persistent disease course, lasting over a year are 25–38.9% over a follow-up period of 5–10 years [9‒11]. Risk factors for a prolonged disease course could not be identified in most studies, possibly because of the small sample size [10]. Additionally, the risk of acquiring the vulgaris phenotype is yet to be fully characterized. Pfingstler et al. [9] revealed that the risk of acquired vulgaris was higher in patients with prolonged GP disease for a year. Svedbom et al. [12] and Ko et al. [10] reported opposing findings, as a majority versus a minority of patients with a persistent disease course had acquired the Vulgaris phenotype. However, no previous study has reported the clinical importance of this event. In this study, we aimed to evaluate the long-term outcomes of new-onset GP and to elucidate which factors are associated with a prolonged disease course and acquired PV phenotype.

This retrospective study included patients with first episode of GP that occurred between 2009 and 2020. The patients were evaluated by board-certified dermatologists at the Dermatology Department of the Sheba Medical Center, Israel. The GP was diagnosed clinically. Detailed data were retrieved from the patients’ medical records. The data retrieved included demographics, disease characteristic and recurrence, treatments applied, response to treatments, family history of psoriasis, and comorbidities. The GP-flaring triggers were also recorded. The triggers were deemed relevant when they occurred up to 3 weeks before the GP flare. Acute streptococcal tonsillitis was diagnosed based on upper respiratory tract symptoms with at least one of the following criteria: throat culture positive for group A β-hemolytic Streptococcus or positive antistreptolysin O (ASLO) titer (>200 μ/mL, taken up to 5 weeks from the onset of symptoms). Of note, the antibody level measured by the ASLO titer starts to rise at 1–3 weeks after a streptococcal infection and peaks at 3–5 weeks but cannot be detected at 5–6 weeks and thereafter [13]. Disease treatments were grouped based on reported product efficacy, with biological treatment being the most potent, followed by oral agents (acitretin, immunosuppressant, and phosphodiesterase 4 inhibitor), phototherapy, and topical steroids.

Current psoriasis severity and extent were rated according to validated patient-reported scales: the Patient Global Assessment of Psoriasis (PGA) scale and Patient Report of Extent of Psoriasis Involvement (PREPI) scale collected from all study participants using a structured telephone questionnaire [14‒17]. At the time of interview, occurring at least a year since the first GP onset, those with psoriatic lesions within the last 3 months were defined as having persistent psoriasis, while those without any psoriatic lesions within the last 3 months were defined as having complete remission.

The PREPI scale is composed of a single question for measuring body surface area (BSA) affected by psoriasis, “If you had to take the palm of your hand and cover up all of the patches of psoriasis on your body today, how many palms of your hand do you think that it would take?” Patients were also instructed that “One palm of your hand is equal to about 1% of your BSA” and “Do not include areas in which psoriasis has faded, leaving only changes in the color of the skin.” The PGA is a five-point severity scale, as previously reported, from 0 = clear to 4 = severe (very marked plaque elevation, scaling, and erythema). Pruritus was rated using the Itch Scale (“no itching” at the 0 point to “severe itching” at the 10 end of the scale). The change in the clinical picture from the GP to PV phenotype was determined by the clinician based on changes in the clinical shape of the lesions from small guttate-sized papules to large scaly plaques with one or more of the following: involvement of the extensor body parts, scalp, or palmoplantar surfaces. Patients were also questioned about having comorbidities: arthritis (whether they were diagnosed by a physician or reported morning stiffness), diabetes, hyperlipidemia, hypertension (whether they were given a physician diagnosis), and obesity (calculated BMI over 30). A follow-up period of less than 12 months and other preexisting psoriasis variants served as the exclusion criteria.

The authors confirm that the ethical policies of the journal, as noted on the journal’s author guidelines page, were adhered to. Ethical approval for this study was obtained from the Research Ethics Committee of the Sheba Medical Center (no. SMC-7082-20). Written informed consent was obtained from participants.

Statistical Analysis

Values are presented as mean (standard deviation) or number (percentage). Categorical variables were compared using the χ2 test, and continuous variables were tested using the independent samples t test. All statistical tests were two-sided, and statistical significance was set at p < 0.05. All data were included in an Excel document, and statistical analyses were performed using SPSS (IBM SPSS Statistics for Windows, version 23.0. Released 2015; IBM Corp., Armonk, NY, USA).

Baseline Characteristics and Disease Course of the Study Population

In total, 120 patients with new-onset GP were included in this retrospective cohort study. Mean age was 28.8 years (±15.2) with 58.3% females. A total of 36.1% of the patients had a family member with psoriasis. The upper respiratory tract infection (URTI) was regarded as a triggering event in 63.3% of the first GP episodes. During follow-up, a single GP flare occurred in a minority of the patients (40.8%), while most patients had multiple GP flares (2–3 flares, 26.7%; over 3 flares, 32.5%). Of all the patients with GP, 17.5% (n = 21) further developed the PV phenotype.

Factors Associated with Persistent Psoriasis

All study patients completed a telephonic questionnaire to assess their current disease state. At that time (average follow-up period of 6.2 years (±3.1)), persistent psoriatic lesions were reported in 49.1% (n = 59) of patients, while the rest had complete remission (50.9%, n = 61). Disease persistence remained high throughout the follow-up period (1–12 years), as illustrated in Figure 1.

Fig. 1.

Prevalence of persistent psoriasis by follow-up years. Rates of disease persistency remained elevated for the entire range of follow-up periods (lasting 1–12 years).

Fig. 1.

Prevalence of persistent psoriasis by follow-up years. Rates of disease persistency remained elevated for the entire range of follow-up periods (lasting 1–12 years).

Close modal

Patient-reported disease severity scales were calculated for patients with persistent disease. A BSA of >10%, indicating severe disease, was reported in 30.5% of the patients. The mean PGA was 1.6 (±0.8), and mean itch index was 3.1 (±3.4) with 54.2% of the patients reporting consistent itchiness. Of those with persistent disease, 72.9% retained the guttate phenotype, while the remaining 27.1% acquired the vulgaris phenotype.

Persistent disease was compared with disease remission (Table 1). Persistent disease was associated with male sex (OR = 2.1; confidence interval [CI], 1.0–4.4), vulgaris phenotype switch (OR = 4.2; CI, 1.4–12.3), and having more than three GP flares (OR = 9.1; CI, 3.5–23.4). Persistent disease was also associated with palmoplantar involvement at the first GP flare (OR = 3.1; CI, 1.0–9.4) or at least one of the GP flares (OR = 5.2; CI, 1.8–15.5). Among patients with persistent disease, severe disease (BSA >10%) was not affected by the disease phenotype (43.8% of the PV phenotype vs. 25.6% of the GP phenotype, p = 0.18). However, the disease phenotype did affect treatment potency, as 43.8% with the vulgaris phenotype compared to 11.6% with the guttate phenotype being treated with oral or biological treatment (OR = 5.9; CI, 1.5–23). Comorbidities, family history of psoriasis, or GP triggering factors were not associated with persistent disease.

Table 1.

Characteristics of patients with persistent GP versus complete remission

 Characteristics of patients with persistent GP versus complete remission
 Characteristics of patients with persistent GP versus complete remission

Factors Associated with Acquired PV Phenotype

Patients with only GP episodes (n = 99) were compared with patients who acquired the PV phenotype (n = 21), as reported in Table 2. The follow-up period was similar in both groups. Patients with multiple GP flares (>3) were found to have higher odds of acquiring the PV phenotype than those with nontransformed GP (52.4% vs. 28.3%; OR = 2.8; CI, 1.1–7.3; respectively). The PV phenotype switch was underrepresented among patients with a single GP flare, compared to nontransformed GP (19.9% vs. 45.5%; OR = 0.28; CI, 0.1–0.9, respectively). Additionally, the PV phenotype was associated with scalp involvement in previous GP flares (81% vs. 50%; OR = 4.3; CI, 1.3–13.5). Furthermore, patients with the PV phenotype were more commonly prescribed potent treatment. Oral or biological treatment at the first GP and over the disease course, respectively, were prescribed in 23.8% and 42.9% of the patients with the PV phenotype versus 7.1% and 11.1% of the nontransformed GP patients (ORs = 6 and 4.1; Cis, 2.1–17.5 and 1.6–14.5, respectively). Sex, family history of psoriasis, comorbidities, or GP triggering factors were found to be associated with acquiring the PV phenotype.

Table 2.

Characteristics of patients who initially presented with GP and acquired PV phenotype (n = 21) compared to patients with nontransformed GP phenotype (n = 99)

 Characteristics of patients who initially presented with GP and acquired PV phenotype (n = 21) compared to patients with nontransformed GP phenotype (n = 99)
 Characteristics of patients who initially presented with GP and acquired PV phenotype (n = 21) compared to patients with nontransformed GP phenotype (n = 99)

This study assessed the long-term outcomes of new-onset GP. In almost half of the patients (49.1%), persistent psoriatic lesions that presented more than a year after GP onset were recorded at the end of follow-up. Although the switch to the vulgaris phenotype was significantly associated with persistent disease, it only occurred in a minority of these patients. Overall, 17.5% of the patients developed PV phenotypes during the follow-up period. Additionally, persistent psoriasis was also associated with male sex, over three GP flares, and palmoplantar involvement.

The long-term outcomes of new-onset GP have been rarely described. A recent comprehensive study by Svedbom et al. [12] prospectively evaluated 116 patients with GP and reported persistent disease rates of 68% at 10 years of follow-up. Importantly, in our study, disease persistence remained elevated during the entire follow-up period (up to 12 years), highlighting the clinical significance of this finding. Contrary to our findings, in the study by Svedbom et al. [12], the majority of patients with persistent disease ultimately acquired the vulgaris phenotype. Ko et al. [10] also reported a persistent GP course of over a year in 38.9% of their retrospective cohort of 36 patients. In line with our findings, only 15% of patients with a persistent disease course transformed to plaque psoriasis, while the rest remained with a guttate phenotype.

In our study, persistent disease end-phenotype affected prognosis, as a significantly larger proportion of the PV phenotype needed oral or biological agents. To the best of our knowledge, this is the first study to assess the clinical importance of acquired PV phenotypes among patients with persistent GP. Although patient-reported severity scales did not differ between the groups, they were completed under treatment. In our study, well-known psoriatic comorbidities were similarly distributed among the entire spectrum of GP presentations, including those who ultimately acquired the PV phenotype. Further studies are needed to assess whether the persistent GP phenotype should practically be regarded as “small plaque” PV, with similar comorbidities and treatment approaches. This seems unlikely from our study, as we found similar comorbidities in both GP and acquired PV phenotypes; however, there is a need for different treatment potency.

Other studies have also reported rates of chronic psoriatic disease. However, these ambiguously define the endpoint of the disease phenotype. Pfingstler et al. [9] reported that in a retrospective cohort of 79 patients with GP, more than a single GP episode was regarded as equivalent to plaque psoriasis, occurring in approximately 25% of the patients. Martin et al. [11] reported that over a follow-up period of 10 years, 5 of 15 (33.3%) patients developed persistent psoriasis. Furthermore, in their study, multiple GP events were recorded in most of the patients. While it is well documented that GP is associated with a family history of psoriasis [7], in our study, it did not predict a switch to the vulgaris phenotype or a persistent disease course. Additionally, the data from our study did not identify URTIs to be associated with persistent disease or development of the vulgaris phenotype. This contrasts with the results of a study by Pfingstler et al. [9] who showed that patients with the acquired vulgaris phenotype were less likely to test positive for streptococci infection. However, only one subgroup of his cohort was tested for throat infections.

Additionally, we identified several predictors associated with a persistent course of psoriasis. At the onset of GP, persistent disease course predictors were male sex and palmoplantar involvement. However, it is unknown whether early therapeutic interventions are helpful in lowering the risk of persistence. Along the GP disease course over three GP flares, the acquired vulvar phenotype was also found to be associated with a persistent disease course.

This study has several limitations, including its retrospective nature, although of a considerably large scale. Second, the endpoint disease severity and extent were based on patient reports; however, validated scales were used [14‒17]. Third, we could not differentiate between bacterial and viral URTI triggers because these data were unavailable for most patients. Further research is required to validate our findings.

In a long-term follow-up study, a persistent GP course of greater than 1 year was common among patients with new-onset GP. A minority of patients with persistent disease acquire the vulgaris phenotype, with a negative impact on disease prognosis. Persistent GP was associated with male sex, over three GP flares, switch to the vulgaris phenotype, and palmoplantar involvement.

A persistent disease course was found to be common among patients with new-onset guttate psoriasis.

This study was approved by the Human Research Ethics Committee of the Sheba Medical Center (No. SMC-7082-20) and was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from participants.

The authors have no conflicts of interest to declare.

The study was conducted without funding sources.

Eran Galili and Sharon Baum: conception and design. Eran Galili, Shir Rubinstein Levy, Ido Tzanani, and Oz Segal: data acquisition and analysis. Anna Lyakhovitsky, Aviv Barzilai, and Sharon Baum: supervision. All authors: critical revision and final approval of the version to be published.

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Further inquiries can be directed to the corresponding author, Eran Galili.

1.
Langley RGB, Krueger GG, Griffiths CEM. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis. 2005;64(Suppl 2):ii18–25.
2.
Psoriasis G. Overview of Guttate Psoriasis, Pathophysiology of Guttate Psoriasis, Epidemiology of Guttate Psoriasis. 2020. (accessed March 30, 2020) Available from: https://emedicine.medscape.com/article/1107850-overview#a3.
3.
Leung DYM, Travers JB, Giorno R, Norris DA, Skinner R, Aelion J, et al. Evidence for a streptococcal superantigen-driven process in acute Guttate psoriasis. J Clin Invest. 1995;96(5):2106–12.
4.
Baker BS, Bokth S, Powles A, Garioch JJ, Lewis H, Valdimarsson H, et al. Group A streptococcal antigen-specific T lymphocytes in guttate psoriatic lesions. Br J Dermatol. 1993;128(5):493–9.
5.
Telfer NR, Chalmers RJG, Whale K, Colman G. The role of streptococcal infection in the initiation of guttate psoriasis. Arch Dermatol. 1992;128(1):39–42.
6.
Diluvio L, Vollmer S, Besgen P, Ellwart JW, Chimenti S, Prinz JC. Identical TCR β-chain rearrangements in streptococcal angina and skin lesions of patients with psoriasis vulgaris. J Immunol. 2006;176:7104–11.
7.
Naldi L, Peli L, Parazzini F, Carrel CF. Family history of psoriasis, stressful life events, and recent infectious disease are risk factors for a first episode of acute guttate psoriasis: results of a case-control study. J Am Acad Dermatol. 2001;44(3):433–8.
8.
Durham GA, Morgan JK. A y-year follow-up study of ninety patients with psoriasis. Br J Dermatol. 1974;91(1):7–11.
9.
Pfingstler LF, Maroon M, Mowad C. Guttate psoriasis outcomes. Cutis. 2016;97(2):140–4.
10.
Ko HC, Jwa SW, Song M, Kim MB, Kwon KS. Clinical course of guttate psoriasis: long-term follow-up study. The J Dermatol. 2010;37(10):894–9.
11.
Martin BA, Chalmers RJG, Telfer NR. How great is the risk of further psoriasis following a single episode of acute guttate psoriasis?. Arch Dermatol. 1996;132(6):717–8.
12.
Svedbom A, Mallbris L, Larsson P, Nikamo P, Wolk K, Kjellman P, et al. Long-term outcomes and prognosis in new-onset psoriasis. JAMA Dermatol. 2021;157(6):1–8.
13.
Sato H, Ishikawa H. Unspecific increase of antistreptolysin-O titer in acute guttate psoriasis. J Dermatol. 1977;4(5):187–91.
14.
Valenzuela F, Paul C, Mallbris L, Tan H, Papacharalambous J, Valdez H, et al. Tofacitinib versus etanercept or placebo in patients with moderate to severe chronic plaque psoriasis: patient-reported outcomes from a Phase 3 study. J Eur Acad Dermatol Venereol. 2016;30(10):1753–9.
15.
Shikiar R, Bresnahan BW, Stone SP, Thompson C, Koo J, Revicki DA. Validity and reliability of patient reported outcomes used in psoriasis: results from two randomized clinical trials. Health Qual Life Outcomes. 2003;1:53.
16.
Dommasch ED, Shin DB, Troxel AB, Margolis DJ, Gelfand JM. Reliability, validity and responsiveness to change of the Patient Report of Extent of Psoriasis Involvement (PREPI) for measuring body surface area affected by psoriasis. Br J Dermatol. 2010;162(4):835–42.
17.
Raychaudhuri SK, Maverakis E, Raychaudhuri SP. Diagnosis and classification of psoriasis. Autoimmun Rev. 2014;13(4–5):490–5.