Nodular prurigo

introduce

Prugo nodularis (PN) is a chronic skin disease that usually manifests as multiple, hard, flesh-colored to pink nodules, usually located on the extensor surfaces of the limbs. The lesions are very itchy and can occur at any age. It is often associated with another skin allergy, such as atopic dermatitis or chronic itching of a different origin. Diagnosis is primarily clinical; although certain conditions may mimic it clinically, requiring differentiation. The condition is associated with significant physical and psychological morbidity and is often difficult to treat. Patients with advanced PN may require a range of general measures, pharmacological approaches, and psychological treatments.

Etiology

The exact cause of prurigo nodularis remains poorly understood. Although the role of an unimpeded itch-scratch cycle is undisputed, the exact sequence of events leading to the final clinical manifestations remains speculative. Nodular prurigo is associated with chronic prurigo and is thought to be a response to repeated scratching in patients with chronic prurigo of various etiologies (including dermatological, systemic, infectious, and neuropsychiatric).

Anecdotal data suggest that infectious agents such as hepatitis C, Helicobacter pylori, Strongyloides stercoralis, mycobacteria, and HIV have a causative role or association in PN.

An increase in the number of epidermal (Merkel cells) and dermal (dermopapillary nerves) sensory structures occurs in PN lesions. Such neural changes are typical of PN and are not seen in chronic lichen simplex or neurodermatitis.

The density of mast cells and neutrophils is increased in PN, although their degranulation products do not appear to be increased. In contrast, while the number of eosinophils remains unchanged, their products, such as major basic protein and eosinophil-derived neurotoxins, show higher than normal levels.

Pruritus in PN appears to be the result of neurogenic inflammation of the skin mediated by various neuropeptides, especially substance P, calcitonin gene-related peptide (CGRP), and vanillic acid receptor subtype 1 (VR-1). The latter combines with capsaicin, making it a potential therapeutic topical agent.

Patients with PN also have elevated levels of interleukin-31 (IL-31), a T-cell-derived, highly pruritic cytokine.

Epidemiology

The exact incidence of PN is unknown. Most patients with PN are between 51 and 65 years of age, but several cases in other age groups have been described. Although the disease affects both men and women, it appears to be more common and more severe in women. Several studies have shown that individuals with specific predispositions develop disease at an earlier age. Race and genetic predisposition appear to play a role, as African Americans are 3.4 times more likely to develop prurigo nodularis than white patients. Other conditions reported to cause prurigo nodularis include internal malignancy, renal failure, and psychiatric disorders. PN has been reported to predict late immunosuppression in HIV-positive patients.

pathophysiology

The pathophysiology of PN remains controversial. Chronic and/or recurrent mechanical trauma or severe frictional attack on the skin causes epidermal hyperplasia, resulting in thickening of the skin. Repeated mechanical friction/scratching can lead not only to the formation of plaques and nodules, and often lichenification; but can also cause discolored changes, usually pigmentation. Pruritus in PN is often episodic, severe, and uncontrollable, and often occurs in discrete spots, eventually transforming into hyperpigmented nodular plaques with scratching, crusting, and sometimes secondary bacteria Infect.

Immunohistochemical studies demonstrated an increased number of dermal nerve fibers in the papillary layer of the dermis. It is hypothesized that weak, unmyelinated epidermal nerves are the conductors of severe prurigo. Nerve growth factor (NGF) and its receptor tyrosine receptor kinase A (TrkA) are overrepresented in PN lesions. They may also be associated with increased release and accumulation of neuropeptides such as substance P and calcitonin gene-related peptide. Interestingly, skin sections collected from PN lesions often show significantly reduced intraepidermal (but not dermal) nerve fiber density. Although this finding raises doubts about whether some subclinical small fiber neuropathy is related to pathophysiology, recent studies suggest that this reduction may actually be secondary to chronic scratching. This was confirmed by observing the recovery of nerve fiber density within the epidermis after complete healing of the lesions.

The role of helper T cell factors (T helper 1 and T helper 2) in the pathogenesis of prurigo nodularis was studied using signal transducers and activators of transcription (STATs) 1, 3, and 6. Only three cases were examined, and the entire epidermis was stained with anti-pSTAT 6, a marker for the Th2 cytokines interleukin (IL)-4, IL-5, and IL-13. These findings suggest that Th2 cytokines play a major role in the pathogenesis of prurigo nodularis.

Histopathology

Histopathological lesions of prurigo nodularis may manifest as thickening, orthokeratosis, irregular epidermal hyperplasia, and pseudoepithelioma-like hyperplasia. Histology of prurigo nodular lesions also shows focal parakeratosis with irregular acanthosis, reduced nerve fiber density, and nonspecific dermal infiltrates containing lymphocytes, macrophages, eosinophils, and neutrophils. . Histology can play an important role in the diagnosis of prurigo nodularis versus lichen simplex and hypertrophic lichen planus. The lesions of lichen simplex rarely show pseudoepithelioma-like hyperplasia or nerve fiber thickening; however, the histological diagnosis of PN cannot be ruled out. It is necessary to correlate clinical and histological findings to reliably differentiate between PN and LS. Both HLP and PN exhibit epidermal hyperplasia, hypergranulation, and dense hyperkeratosis. An increase in the number of vertically aligned collagen fibers in the dermis as well as fibroblasts and capillaries was found in both cases. However, basal cell degeneration was limited to the tips of the reticular ridges, and no band-like inflammation was seen in HLP and PN .

history and body

People with prurigo nodularis develop characteristic hard, dome-shaped, itchy nodules that range in size from a few millimeters to centimeters. Nodules can be flesh-colored, erythematous, pink, and brown/black. Initially, lesions may start as normal skin or dry areas. Due to the itching, the patient will begin and continue to scratch the affected area until a dome-shaped nodule forms. Typically, lesions appear symmetrically on the extensor surfaces of the patient's arms and legs. Lesions may also be found in the occipital region of the scalp. The upper back, abdomen, and sacrum may also be affected. Typically, hard-to-reach areas such as the upper mid-back are not affected. This discovery is called the "butterfly sign." The palms of the hands, soles of the feet, face, and flexed areas are usually not affected. People with prurigo nodularis experience severe itching, which can be very painful. It can be sporadic or continuous and can worsen with sweating, irritation from clothing, or heat. Patients experience a variety of itching sensations, including burning, stinging, and temperature changes in the lesions. In some cases, atopic dermatitis sicca has been reported to coexist with prurigo nodularis and may be a trigger. Due to the itching caused by PN, the lesions often appear as scratches. Exfoliated lesions are at increased risk for secondary infection and, if infected, may develop crusting, erythema, or pain. Nodular prurigo may also occur in the setting of an underlying local dermatologic disorder, such as venous stasis, postherpetic neuralgia, or brachioradial pruritus.

Evaluate

Prurigo nodularis is a clinical diagnosis. Patients with nodular prurigo may have a history of chronic severe itching, accompanied by scratches and flesh-colored, pink nodular lesions on the extensor muscle surfaces. Dermoscopy may be a useful tool in the diagnosis of PN and HLP. In one study, dermoscopic examination of HLP revealed pearly white areas and peripheral streaks, grey-blue globular comedone-like openings, red dots and globules, brown-black globules, and yellowish structures. PN dermoscopy shows red dots, globules, and pearly white areas with surrounding streaks. A skin biopsy may be necessary for lesions that are bleeding, ulcerated, or resistant to first-line treatment. If patients with nodular prurigo and severe prurigo have no cause for their pruritus, they should be evaluated for causes of chronic pruritus. Causes of severe itching may include kidney disease, liver disease, thyroid disease, HIV infection, malignant tumors, or parasitic infections. Evaluation for these causes includes a complete blood count (CBC), complete metabolic panel, thyroid studies (including TSH and free T4), urinalysis, stool test, HIV antibodies, and chest X-ray. Serum IgE levels may also be elevated in patients with PN and atopic dermatitis.

Treatment/Management

Treatment of prurigo nodularis requires a multifaceted approach. Patients need to be educated on practical practices for reducing scratching lesions, identifying and diagnosing the underlying cause of itching, and diagnosing and treating any psychological disorders associated with scratching and skin-picking. The goal of topical and systemic treatments is to disrupt the itch-scratch cycle.

general care

• Patients are encouraged to keep their nails short, wear protective clothing such as long sleeves and gloves, and cover the nodules with a bandage.
• Bathing with a mild cleanser and applying an emollient several times a day to keep the skin moisturized should be encouraged.
• Calamine lotion and lotions containing menthol and camphor can relieve itching.
• Stay in a cool and comfortable environment.
• relieve pressure.

special care

Local and intralesional treatment

• Although randomized trials have not yet been conducted, topical treatments for prurigo nodularis include a class of topical corticosteroids, intralesional corticosteroids, topical calcineurin inhibitors, topical capsaicin, and topical vitamin D analogs.
• The recommended first-line treatment is topical corticosteroids, such as 0.05% clobetasol dipropionate ointment, sealed with plastic wrap and applied once at night for at least 2 to 4 weeks.
• Intralesional injection of triamcinolone acetonide at concentrations of 10 mg/mL to 20 mg/mL has been shown to flatten skin lesions and relieve pruritus.
• Pimecrolimus 1% is as effective as hydrocortisone and can be taken long-term.
• Calcipotriol ointment is more effective than betamethasone valerate 0.1%.
• Low concentrations (less than 5%) of menthol can relieve itching by increasing the itch stimulation threshold.

Antihistamine and Leucin inhibitors

• Take a high-dose non-sedating antihistamine during the day, followed by a first-generation sedating antihistamine at bedtime. The combination of fexofenadine and montelukast works well. Common adverse effects of antihistamines are drowsiness, dizziness, and weakness.

Phototherapy/Excimer Therapy

• PUVA phototherapy, including bath/topical PUVA, UVA, narrowband UVB, and 308 nm monochromatic excimer light, has been used and shown improvement in patients with prurigo nodularis.
• Narrow-band UVB phototherapy with an average dose of 23.88-26.00 j/cm2 can significantly improve prurigo nodularis.
• Excimer laser is more beneficial than topical clobetasol.

Oral immunosuppressants

• As with topical therapies, randomized trials involving the use of these systemic therapies have not been reported, and the benefits and risks of the drugs must be considered before initiating treatment
• Oral immunosuppressive therapy should be considered in patients with severe, refractory nodular prurigo.
• A single-institution retrospective study showed that cyclosporine at a mean dose of 3.1 mg/kg improved clinical symptoms and reduced pruritus.
• Methotrexate at weekly doses of 5-20 mg/kg showed complete or partial response for 2.4 months. The average duration of response in these patients was 19 months.
• Treatment with azathioprine and cyclophosphamide has also been reported to be successful.
• Oral tacrolimus treatment significantly reduced prurigo symptoms in patients previously treated with cyclosporine for prurigo nodularis.
• Three cycles of intravenous immune globulin followed by a combination of methotrexate and topical steroids are effective in prurigo nodularis associated with atopic dermatitis.

Novel treatments

• Thalidomide and lenalidomide. Thalidomide is an immunomodulator that has both central and peripheral depressant effects and inhibits tumor necrosis factor-α. Lenalidomide, a more potent molecular form of thalidomide, is effective in prurigo nodularis and has fewer side effects. Frequency of peripheral neuropathy.
• Selective serotonin reuptake inhibitors and tricyclic antidepressants may also be considered for the treatment of chronic pruritus. It is also important for patients to see a doctor with a mental health professional.
• Naloxone and naltrexone exert their antipruritic effects by inhibiting Mu-opioid receptors on nociceptive neurons and interneurons, thus suppressing itching.
• The NK1r antagonists aprepitant and serlopitant block substance P-mediated signaling in the pathogenesis of prurigo nodularis. Patients with nodular prurigo experienced significant relief of itching after receiving aprepitant monotherapy.
• The IL 31 receptor antibody Nemolizumab significantly improved pruritus scores in patients with moderate to severe atopic dermatitis. However, its role in prurigo nodularis remains unclear.

Differential diagnosis

• lichen simplex chronicus
• hypertrophic lichen planus
• nodular pemphigoid
• nodular scabies
• keloid scar
• dermatofibroma
• foreign body reaction

treatment plan

Treatment of prurigo nodularis should be tailored to the patient's age, comorbidities, severity of prurigo, quality of life, and expected side effects.

first row

• Long-term use of Class 1 topical steroids (clobetasol propionate 0.05%, halobetasol propionate 0.05%) can lead to adverse reactions such as skin atrophy, folliculitis, prickly heat, delayed wound healing, and tachyphylaxis.
• Triamcinolone acetonide (40 mg/ml) was injected into the lesion. This may be accompanied by cryotherapy.
• Topical menthol solutions are available in concentrations less than 5%.
• Systemic antihistamines: Take fexofenadine 180mg, levocetirizine 5mg or desloratadine 5mg during the day, and take hydroxyzine 25mg at night and other sedative antihistamines. First-generation antihistamines can cause side effects such as sedation, hyperarousal, impaired cognitive function, dry mouth, constipation, difficulty urinating, tachycardia, and arrhythmias.

second line

• Phototherapy: PUVA, long-wave UVA, narrow-band UVB, 308nm monochromatic excimer light
• Systemic immunosuppressant: cyclosporine 3mg/kg daily. Adverse reactions include nephrotoxicity, hypertension, hyperlipidemia, hyperkalemia, and hyperuricemia. Methotrexate 5-20 mg/week. Common adverse reactions are nausea, gastrointestinal symptoms, and transaminitis.
• Thalidomide produces a good response at 300-400 mg daily for 3 months, with subsequent dose reduction to 50 mg daily. However, discontinuing the drug completely can lead to relapse. Adverse effects are teratogenicity and peripheral neuropathy. Lenalidomide at 5-10 mg daily is less neurotoxic than thalidomide.
• Opiate receptor antagonist: naltrexone 50 mg daily. Adverse reactions were limited to the first two weeks of treatment and included nausea, fatigue, dizziness, heartburn, and diarrhea.

prognosis

Prurigo nodularis is a benign disease with a good prognosis. This is a chronic condition that often has an underlying cause of the itching. However, prurigo nodularis is a distinct entity from these underlying causes and may persist despite resolution of the precipitating factor.

complication

Nodular prurigo lesions can become secondary infected by scratching the lesions. It is important to monitor for clinical signs of infection such as erythema, pain, fever, and fever. If secondary infection is suspected, it is important to initiate appropriate topical or systemic antibiotic therapy to cover the skin flora.

Deterrence and patient education

Barriers to the treatment of prurigo nodularis are severe prurigo nodularis that may lead to psychological distress, the chronic nature of the condition, the length of treatment, and the potential side effects of medications.

Discussions with patients should include the advantages and disadvantages of treatment, side effects, and possible use of off-label medications. Therefore, patient education can promote treatment compliance. The potential length of treatment should also be discussed, as prurigo nodularis is difficult to treat and patients may become frustrated with the lack of improvement.

Improve healthcare team outcomes

Treatment of prurigo nodularis requires an interprofessional team that includes primary caregivers, nurse practitioners, dermatologists, and mental health nurses. Patients need to be educated on practical practices for reducing scratching lesions, identifying and diagnosing the underlying cause of itching, and diagnosing and treating any psychological disorders associated with scratching and skin-picking. The goal of topical and systemic treatments is to disrupt the itch-scratch cycle. Patients are encouraged to keep their nails short, wear protective clothing such as long sleeves and gloves, and cover the nodules with a bandage. Bathing with a mild cleanser and applying an emollient several times a day to keep the skin moisturized should be encouraged. Calamine lotion and lotions containing menthol and camphor-like sanitizer can relieve itching. First-generation sedating antihistamines (such as hydroxyzine taken at bedtime) may help control nighttime itching. Selective serotonin reuptake inhibitors and tricyclic antidepressants may also be considered for the treatment of chronic pruritus.

Finally, pharmacists should educate patients about potential adverse effects of medications and report complications to the clinical team when they occur.