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Inverse psoriasis

Inverse psoriasis, also known as flexural or psoriasis, is a variant of plaque psoriasis that manifests as smooth, shiny, erythematous patches in the folds of the body, such as the armpits, , inframammary region, and anogenital area. Unlike typical plaque psoriasis, it features minimal or absent due to the moist environment of these areas, often presenting with itching, soreness, and a glossy appearance that may appear purplish, brown, or darker on skin of color and on lighter skin tones. This condition arises from an immune-mediated inflammatory process similar to other forms of , where overactive T cells trigger rapid cell proliferation, leading to the characteristic lesions. The prevalence of inverse psoriasis among individuals with varies widely, estimated at 3% to 36%, influenced by diagnostic criteria and whether genital involvement is included, though it commonly affects 21% to 30% of patients, particularly those who are or have deep . It can occur at any age, including as napkin psoriasis in infants, and may be triggered by factors such as , infections (including fungal or bacterial colonization in moist areas), , use, , or certain medications. is primarily clinical, based on the location and appearance of lesions, with dermoscopy revealing distinctive "bushy" capillary patterns to differentiate it from similar conditions like , , or tinea infections; a may be performed if uncertainty exists. The condition often impacts due to , , and potential secondary infections in the occluded areas, and it shares the chronic, relapsing nature of with risks for comorbidities such as , , and . Treatment focuses on reducing and managing symptoms, as there is no , with first-line options including low- to mid-potency topical corticosteroids (e.g., betamethasone, achieving up to 86% improvement in severity scores), inhibitors (e.g., ), and analogs (e.g., calcipotriol). For more severe or widespread cases, systemic therapies such as , cyclosporine, or biologics (e.g., ixekizumab, clearing up to 73% of genital lesions) may be employed, alongside supportive measures like emollients, agents for superinfections, and keeping the skin dry with powders to prevent . Phototherapy can be useful but requires caution in fold areas to avoid Koebnerization, and lifestyle modifications—such as and trigger avoidance—play a key role in long-term control.

Definition and Characteristics

Definition

Inverse psoriasis is an immune-mediated inflammatory classified as a subtype of , characterized by the development of smooth, shiny, erythematous plaques in flexural or areas where occur, such as the armpits, , inframammary folds, and gluteal cleft. Unlike typical plaque psoriasis, these lesions lack the thick, silvery scales commonly seen elsewhere on the body, as the and in prevent scale formation. This variant is also referred to as flexural psoriasis due to its preferential involvement of body creases. The appearance of inverse psoriasis lesions can vary by skin tone; on lighter skin, they present as bright red and glossy patches, while on skin of color, they may appear violaceous, brown, or hyperpigmented relative to surrounding areas. These plaques are often well-demarcated and may be accompanied by fissuring in deeper folds, contributing to discomfort in affected regions.

Distinction from Other Psoriasis Types

Inverse psoriasis, also known as flexural psoriasis, primarily affects such as the armpits, , and inframammary regions, presenting as smooth, erythematous patches without the thick, silvery scales characteristic of plaque , which typically occurs on extensor surfaces like the elbows and knees. The absence of scaling in inverse psoriasis results from the moist environment and friction in areas, making lesions appear smoother and more prone to secondary bacterial or fungal infections compared to the drier, scaly plaques of the more common plaque variant, which accounts for 80-90% of cases. Unlike , which manifests as numerous small, drop-shaped lesions often triggered by streptococcal infections and appearing acutely on the trunk, inverse psoriasis is and not associated with such infectious precipitants, instead exacerbated by heat, sweat, or in flexural sites. In contrast to , which features sterile pustules either localized to palms and soles or widespread in severe forms, or erythrodermic psoriasis involving over 90% of the body surface with intense and exfoliation, inverse psoriasis remains confined to without pustule formation or systemic exfoliative involvement. Although all psoriasis variants share an underlying autoimmune mechanism involving T-cell mediated inflammation, up to 21-30% of individuals with psoriasis may develop inverse lesions alongside other forms like plaque, with the intertriginous distribution serving as a key distinguishing feature in mixed presentations.

Clinical Presentation

Signs and Symptoms

Inverse psoriasis manifests as well-demarcated, erythematous plaques that appear smooth and shiny, with minimal to no scaling due to the moist environment of affected skin folds. These lesions often exhibit superficial erosions, fissuring, or maceration, contributing to a glossy, inflamed appearance. Patients commonly experience primary symptoms of intense itching, soreness, and a burning sensation, which can significantly impact daily comfort. These sensations are frequently exacerbated by sweating and , as the occluded areas trap moisture and promote irritation. Lesion appearance varies by skin tone: on lighter skin, the plaques typically present as bright red, while on darker skin tones, they may appear purple-brown or darker than the surrounding . Secondary bacterial or fungal , common in these moist sites, can lead to white scaling overlying the inflamed areas. Symptom severity is generally mild to moderate, including pain that is particularly noticeable in regions such as the or under the breasts, and it often intensifies with factors like or , which increase and .

Epidemiology and Risk Factors

The prevalence of inverse psoriasis among individuals with psoriasis varies from 3% to 36%, commonly estimated at 21% to 30%. This subtype is more prevalent among individuals who are or obese, as excess body weight can exacerbate skin fold involvement, with studies indicating that a (BMI) greater than 30 is associated with approximately a 1.5- to 2.7-fold increased risk of developing psoriasis, including inverse forms. Onset typically occurs in adulthood, most commonly between the ages of 20 and 40 years, though it can appear at any age. The condition is often underdiagnosed in individuals with skin of color, where lesions may present with less scaling and more or , leading to misattribution to other flexural dermatoses. A family history of substantially elevates risk, with first-degree relatives of affected individuals facing up to a 10-fold higher likelihood of developing the condition compared to the general population. Inverse , like other forms, is linked to several associated conditions, including , mellitus, and , reflecting shared inflammatory pathways that increase comorbidity prevalence by 1.5- to 2-fold in affected patients. Obesity is associated with increased incidence of psoriasis, including inverse forms, amid the ongoing obesity epidemic.

Pathophysiology

Genetic and Immune Mechanisms

Inverse psoriasis shares a genetic foundation with other psoriasis subtypes, characterized by polygenic inheritance involving more than 80 susceptibility loci identified through genome-wide association studies (GWAS). These loci collectively contribute to disease risk, with the major histocompatibility complex (MHC) region, particularly the PSORS1 locus, accounting for the largest heritability fraction, estimated at 35-50%. The HLA-Cw6 allele within PSORS1 is the strongest individual risk factor, associated with psoriasis susceptibility in approximately 50% of cases across populations, and linked to earlier onset and more severe manifestations. Although specific prevalence data for inverse psoriasis are limited, this allele's role underscores the shared genetic architecture with plaque psoriasis. Immune dysregulation in inverse psoriasis centers on T-cell-mediated , where autoreactive CD4+ and CD8+ T cells infiltrate the skin and drive chronic immune activation. Key cytokines, including interleukin-17 (IL-17), IL-23, and tumor necrosis factor-alpha (TNF-α), are overproduced by Th17 cells and dendritic cells, amplifying the inflammatory cascade. IL-23 promotes Th17 differentiation and IL-17 secretion, which synergizes with TNF-α to induce proliferation and release, sustaining the cycle of . This dysregulation leads to epidermal hyperproliferation, manifesting as acanthosis—thickening of the spinous layer—without the pronounced typical of plaque , owing to the moist flexural environment that limits scale formation. Pathologically, inverse psoriasis exhibits , characterized by intercellular edema in the , alongside a thinned or reduced due to frictional moisture in areas. These features reflect barrier disruption mediated by innate immune responses, including activation of plasmacytoid dendritic cells and release of like cathelicidin, which exacerbate local . Neutrophilic infiltration in the and scale is common, further contributing to the erythematous, erosive lesions observed. Recent 2025 GWAS meta-analyses have advanced understanding by identifying novel susceptibility loci for and confirming polygenic risk contributions, though inverse-specific variants remain under investigation. These studies emphasize the IL-23/Th17 axis as a convergent therapeutic target across variants.

Environmental Triggers

Inverse , affecting such as the armpits, , and inframammary regions, is particularly susceptible to by environmental factors that promote and microbial in occluded areas. from skin-to-skin rubbing, often intensified in individuals with deeper folds, leads to intertrigo-like and can precipitate flares. Moisture accumulation due to in these areas fosters and superficial erosions, while sweating—exacerbated by or humid environments—further aggravates soreness and itching. Lifestyle elements play a significant role in triggering or worsening inverse psoriasis. Obesity increases mechanical pressure on skin folds, promoting friction and moisture retention, which heightens the risk of onset and severity; studies indicate a twofold increased risk of psoriasis in obese individuals compared to those of normal weight. Tight clothing, synthetic fabrics, or wool can trap heat and moisture, while hot climates amplify sweating and irritation in affected areas. Infections and irritants are common precipitants, especially in the warm, moist milieu of . Candida overgrowth thrives in these conditions, leading to secondary superinfections that mimic or trigger inverse psoriasis flares, though the exact role of microbial colonization remains debated. Irritants such as soaps, latex, or other allergens can provoke upon contact with sensitive flexural skin. Additional factors include , which may indirectly heighten immune responses to these environmental insults, and , associated with a 1.5- to 2-fold increased risk of development and flares through inflammatory mechanisms. Hormonal changes in women, such as those during , , or , can fluctuate disease severity, potentially worsening symptoms in inverse psoriasis.

Diagnosis

Clinical Assessment

The clinical assessment of inverse psoriasis begins with a detailed patient history to identify key risk factors and symptom patterns. Clinicians inquire about family history of , as plays a significant role in its development. The duration of symptoms is evaluated, along with aggravating factors such as friction from , sweating, infections, , or skin injuries that may exacerbate lesions. During the physical examination, the dermatologist inspects the affected areas, focusing on flexural sites like the axillae, , inframammary folds, and for characteristic smooth, well-demarcated, erythematous plaques that lack scaling due to the moist environment. assesses for tenderness or in these regions, and variations in tone are noted, with lesions appearing bright red on lighter skin or purple-ish, brown, or darker on skin of color. Diagnosis relies on clinical , as there are no specific diagnostic criteria unique to inverse psoriasis; instead, the presentation in areas guides identification. The (PASI) may be adapted to assess severity, though modifications account for the absence of in these lesions. Symptom overlap with conditions like can occur, necessitating careful differentiation through history and exam. According to (AAD) guidelines, dermatologists play a crucial role in early recognition of inverse psoriasis to mitigate complications such as secondary infections in occluded areas.

Differential Diagnosis and Tests

Inverse psoriasis, characterized by smooth, erythematous plaques in flexural areas, must be differentiated from other conditions that cause similar eruptions, including due to mechanical friction, fungal infections such as or , bacterial infections like , seborrheic dermatitis, , and . Less common mimics include , , and Zoon's plasma cell mucositis. Diagnostic confirmation often requires targeted tests to exclude infections and confirm psoriatic changes, as clinical overlap with these entities can lead to frequent misdiagnosis, particularly in isolated flexural lesions; one study reported initial misdiagnosis in up to 40% of cases with exclusive flexural involvement, often attributed to infectious . Dermoscopy may aid differentiation by revealing distinctive "bushy" patterns and dots. A (KOH) preparation of skin scrapings is commonly performed to rule out fungal elements like or hyphae in suspected or . Swab cultures for bacterial or fungal pathogens are recommended if secondary is suspected, helping to identify organisms such as in . Skin biopsy is reserved for atypical or refractory cases but provides definitive evidence through histopathology revealing psoriasiform dermatitis with epidermal hyperplasia, elongated rete ridges, parakeratosis, thinned suprapapillary plates, and occasional Munro microabscesses. Direct immunofluorescence is rarely needed unless autoimmune blistering disorders are considered in the differential. Routine blood tests or imaging are not indicated unless systemic involvement or complications like psoriatic arthritis are suspected, though baseline labs may be obtained prior to initiating therapies.

Management and Treatment

Topical and Localized Therapies

Topical therapies form the cornerstone of management for inverse psoriasis, particularly given the location in flexural areas where the skin is thin, moist, and prone to from stronger agents. These treatments aim to reduce , alleviate symptoms like itching and soreness, and prevent secondary infections without causing or other adverse effects common in occluded regions. Low-potency formulations are preferred to minimize risks, with application typically limited to short durations and monitored closely. Corticosteroids remain a first-line option for mild to moderate inverse psoriasis, with low-potency agents such as hydrocortisone 1% or mid-potency options like fluticasone propionate 0.005% recommended for sensitive intertriginous sites to curb inflammation effectively while reducing the risk of skin thinning. These are applied once or twice daily for 2 to 4 weeks, followed by tapering to avoid side effects like telangiectasia or striae, which are heightened in flexural areas due to occlusion. Clinical evidence indicates that such regimens achieve over 50% improvement in lesion severity, with higher-potency variants like betamethasone 0.1% reserved for refractory cases, yielding up to 86% reduction in modified Psoriasis Area and Severity Index (m-PASI) scores in targeted studies. Calcineurin inhibitors, including 0.1% ointment and 1% cream, serve as effective steroid-sparing alternatives, particularly for long-term maintenance in or genital involvement where from corticosteroids is a concern. These non-steroidal topicals inhibit T-cell to dampen immune responses, demonstrating clearance or significant improvement in 65% to 71% of patients across trials focused on and psoriasis. Applied twice daily, they may initially cause transient burning or pruritus but offer a favorable safety profile for extended use in moist folds. Additional topical agents complement these core treatments, tailored to specific needs in inverse psoriasis. Vitamin D analogs such as calcipotriene or ointment slow proliferation and are suitable for flexural areas, with calcitriol showing 67% efficacy in clearance rates compared to 33% for calcipotriol in sensitive sites; they are often combined with low-potency corticosteroids for enhanced results. preparations, while versatile for , require dilution with a to prevent in and are applied sparingly to reduce scaling. Antifungals like clotrimazole are incorporated if secondary candidal s arise, common in occluded areas, to address both psoriasis and microbial overgrowth. Moisture barriers, including zinc oxide pastes or absorbent powders, help maintain dryness in intertriginous zones, thereby reducing and risk. As of 2025, novel non-steroidal topicals like , an , have gained traction for inverse due to its once-daily application, anti-inflammatory effects, and suitability for sensitive areas without steroid-related risks. Approved initially for plaque , it has demonstrated safety and efficacy in flexural involvement, providing sustained remission and relief in clinical use.

Systemic and Advanced Therapies

For moderate-to-severe inverse psoriasis that does not respond adequately to topical therapies, systemic treatments are employed to address widespread and immune dysregulation. Oral medications such as , administered at doses of 7.5 to 25 mg weekly, have demonstrated efficacy in controlling severe cases by suppressing immune activity and reducing lesion severity. Cyclosporine is utilized for short-term management in acute flares, typically at 3 to 5 mg/kg daily, offering rapid clearance but limited to 3 to 6 months due to potential renal toxicity. , an oral dosed at 25 to 50 mg daily, is particularly beneficial in cases with hyperkeratotic features overlapping inverse psoriasis, as it normalizes keratinization and enhances skin barrier function. Biologic therapies targeting key cytokines provide high efficacy for refractory inverse psoriasis, especially in flexural areas. Interleukin-17 (IL-17) inhibitors, including (300 mg subcutaneously every 4 weeks after loading) and ixekizumab (160 mg loading dose followed by 80 mg every 4 weeks), achieve significant improvement in 70-80% of patients with genital and inverse involvement, with ixekizumab yielding 73% clear or almost clear static Physician Global Assessment (sPGA) scores for genital skin at week 12. Interleukin-23 (IL-23) inhibitors like (100 mg subcutaneously at weeks 0 and 4, then every 8 weeks) offer sustained responses, with real-world data showing progressive effectiveness over time in inverse psoriasis cohorts, though with a slightly slower onset compared to IL-17 agents. Overall, these biologics report response rates of 80-90% in flexural psoriasis subsets, prioritizing patient tolerability in sensitive areas. Phototherapy serves as a non-pharmacologic systemic option, with B (NB-UVB) adapted for sites by using lower doses (initially 0.1-0.3 J/cm², escalating cautiously) to minimize irritation in moist folds while achieving clearance in 60-80% of cases after 20-30 sessions. The (308 nm) enables targeted delivery to localized flexural plaques, delivering higher fluence (up to 16 J/cm²) with fewer sessions (8-12) and reduced risk of adjacent skin exposure, proving effective for resistant lesions. As of 2025, (JAK) inhibitors represent emerging options for refractory inverse psoriasis. , an oral TYK2 inhibitor dosed at 6 mg daily, has shown successful clearance in case reports of inverse psoriasis unresponsive to prior therapies, with sustained remission over 12 months and a favorable safety profile.

Prognosis and Complications

Disease Course and Outlook

Inverse psoriasis follows a relapsing course, characterized by periods of flare-ups interspersed with remission phases that can last for months or years. Flares are often triggered by factors such as , which exacerbates skin fold , and , including streptococcal or fungal overgrowth in affected areas. Remission is achievable and more sustained with consistent treatment adherence, including topical therapies and lifestyle modifications to minimize triggers. Prognostic factors include body weight, with non-obese patients experiencing better disease control and response to therapies due to reduced and improved drug efficacy. Combined therapies, such as biologics with topicals, can enable significant improvement in clearance for many patients with moderate-to-severe . Regular follow-ups are essential for monitoring disease activity, adjusting treatments, and preventing complications from untreated flares. The condition significantly impacts , with genital involvement—a common feature of inverse psoriasis—leading to discomfort, embarrassment, and sexual health challenges such as avoidance of intimacy or pain during activity. As of 2025, emerging evidence suggests that early initiation of biologics may alter the disease course, leading to improved long-term outcomes and higher rates of skin clearance.

Associated Risks and Prevention

Inverse psoriasis, due to its location in skin folds, carries risks of secondary infections from bacteria or fungi thriving in moist environments. These infections, such as candidiasis or dermatophytosis, can manifest as pus-filled bumps, swelling, or foul odor, and may progress to more serious conditions like cellulitis if untreated. In severe cases, persistent scratching or fissuring can lead to delayed healing and potential scarring, though psoriasis itself rarely causes permanent scars. Additionally, individuals with psoriasis, including the inverse subtype, face an elevated risk of , with meta-analyses reporting a risk ratio of 2.53 (95% CI, 1.65-3.89) for compared to the general population. Individuals with inverse psoriasis, like those with other psoriasis subtypes, have an elevated risk of developing . Preventive strategies focus on minimizing , , and triggers to reduce frequency and risk. Weight management is key, as exacerbates symptoms in flexural areas; studies show that a 5-10% body weight reduction can decrease severity and improve treatment response. Wearing loose, breathable clothing made from or moisture-wicking fabrics helps prevent irritation and sweat accumulation in affected areas. Gentle hygiene practices are essential: bathe daily in lukewarm using mild, fragrance-free soaps to avoid drying out or irritating sensitive , then pat dry thoroughly and apply moisturizers or absorbent powders to keep folds dry. modifications include reduction through or exercise, as can trigger flares, and , which lowers overall exacerbation risk. In humid climates, where moisture promotes fungal overgrowth, prophylactic agents may be recommended for those prone to recurrent infections, as emphasized in recent updates highlighting intertriginous vulnerability.

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