Having pruritic skin lesions means that you may be dealing with a skin disease. T-cell prolymphocytic leukaemia, Prurigo, and atopic dermatitis are examples of these diseases.These skin diseases are known to cause irritation and inflammation of the skin.
Atopic Dermatitis
Atopic dermatitis is a chronic inflammatory skin disease characterised by the production of immunoglobulin E (IgE) and the accumulation of lymphocytes in the skin. Its symptoms include erythematous papules, skin rashes, pruritus, and inflammation. Atopic dermatitis is caused by a number of pathogenic mechanisms, including the disruption of the skin barrier, lipid defects, and protease defects.
Using atopic dermatitis as a model for research, various studies have been conducted to understand the cellular and molecular mechanisms involved in atopic dermatitis. These studies provide insights into the mechanisms of itch and inflammation and predict the development of newer, more targeted molecular therapies.
Atopic dermatitis is often characterised by an itch that is severe and persistent. The itch may be localised to a specific area of the body or may be more widespread. This type of itching is often accompanied by pruritus, a tingling sensation that can lead to scratching. Itching that breaks the skin is a medical emergency. In severe cases, infection is possible.
Animal models provide insights into the mechanisms of itch and have helped develop more balanced approaches to atopic dermatitis. Several targeted systemic immunosuppressants are in development for atopic dermatitis. These immunosuppressants block T-cell function and inhibit inflammatory responses. These immunosuppressants are indicated for widespread atopic dermatitis or recalcitrant atopic dermatitis.
Some studies have indicated that the effects of antihistamines on cutaneous nerves may be beneficial in conditions involving dry skin. These antihistamines may also improve skin barrier function.
Research on itch and inflammation has also focused on signalling pathways that contribute to proliferation, differentiation, and spongiosis. These pathways are responsible for the generation of proinflammatory factors and the formation of the stratum corneum barrier. The CXCR3 chemokine receptor signalling pathway is important for itching in allergic contact dermatitis.
Prurigo Diseases
Several diseases are associated with prurigo skin lesions. Atopic dermatitis is one of them. It is characterised by itching and red papules. Symptoms of atopic dermatitis can be reversible. If it is not reversible, it can result in scarring.
Prurigo nodularis (PN) is a chronic inflammatory skin disease. The disorder disproportionately affects people of African ancestry. Its pathophysiological mechanisms are unclear, although it is believed to involve inflammation. It is also known to be linked to various dermatologic, neurologic, and metabolic processes.
To gain insight into the pathophysiology of PN, the researchers conducted an analysis of PBMCs and skin biopsies from 13 adult patients with the disease. They compared gene expression using RNA sequencing with immunohistochemistry validation. The results showed increased gdT cells and IL-22 cytokine expression in PN. The pathophysiology of PN has also been linked to neuronal sensitization, which may contribute to the disease.
The results suggest that IL-31 may play a relevant role in Th2-mediated inflammation. It has also been shown to crosstalk with eosinophils, which may contribute to the pathogenesis of PN. The IL-31 receptor is located on the surface of the cell membrane of epidermal keratinocytes, and its signalling may also affect the generation of M2-type anti-inflammatory macrophage responses.
In addition, the researchers also explored the role of CGRP, a hormone released by the nerve fibers. They found that CGRP expression has increased in the nerve fibres. This is supported by studies of nerve tissue in patients with chronic prurigo.
To better understand the pathophysiology of PN, more basic research efforts are needed. Identifying the underlying cause of the disease and developing more effective treatments are important goals.
Prurigo nodularis lacks FDA-approved therapies. Therefore, further studies are needed to develop targeted drugs.
T-cell prolymphocytic leukaemia
Despite being a rare leukemia, T-cell prolymphocytic leukaemia (T-PLL) is frequently associated with pruritic skin lesions.Its cutaneous involvement is usually asymptomatic, and patients may not need treatment at diagnosis. However, its prognosis is poor.
Approximately 2% of all chronic leukemias are T-PLLs. These leukemias are rare and have a short median overall survival. T-PLL has no formal staging system. However, a subset of patients may progress to a more aggressive disease. The clinical manifestations of T-PLL include atypical lymphoid infiltrates on the skin, splenomegaly, lymphocytosis, and bone marrow infiltration. It is also associated with a high incidence of non-histaminergic pruritus.
T-PLL is a mature T-cell malignancy that tends to occur in adults. Unlike atypical lymphoid infiltrates, these neoplastic cells are usually CD4+ post-thymic T cells. A CD4 or CD8 immunophenotype is present in 60% of cases.
The T cell receptor (TCR) recognises peptides bound to major histocompatibility complex (MHC) molecules, which activates T lymphocytes. This process is mediated by the associated enzymes and co-receptors. The TCR is a receptor that normally recognises peptides that are matched to MHC class II molecules on the surface of antigen-presenting cells. In lymphomas, clonal TCR rearrangements occur, and the neoplastic cells show an activated cytotoxic immunophenotype.
A patient presented with an atypical cutaneous leukaemia that presented with pruritic skin lesions and a history of type 2 diabetes. Initial biopsies found pseudoepitheliomatous hyperplasia and atypical lymphoid infiltrates. A peripheral blood smear revealed small- to medium-sized lymphocyte proliferation but no hepatosplenomegaly.
The patient was treated with alemtuzumab, but this therapy was discontinued due to reactivation of the cytomegalovirus. The patient then developed symmetrical palmoplantar hyperkeratosis. The patient’s HTLV-1 serology was positive.
Unclassifiable cell lymphoma
Among the primary cutaneous lymphomas, unclassifiable cell lymphoma is one of the least well studied. It is characterised by intermediate features between diffuse large B-cell lymphoma (DLBCL) and cHL. It is not associated with medullar infiltration. It usually presents as a psoriasis-like patch or a nodular skin rash. The clinical course is indolent. The cutaneous lesions are typically treated as dermatitis artefacta.
Unclassifiable cell lymphoma can be distinguished from MGZL by its expression of B-cell markers. It is important to perform cytogenetic tests for accurate lymphoma classification. Some centres do not perform cytogenetic tests routinely on lymphoma samples.
Unclassifiable cell lymphoma should be considered when a patient presents with intense pruritus. A skin biopsy is useful in diagnosing this condition. In this case, the gross specimen showed an uneven granular layer and lymphocytes in the dermis. A photomicrograph of these monomorphic lymphoid cells showed moderately amphophilic cytoplasm, round to oval nuclei, epidermotropism, and EX100 expression.
A 19-year-old woman presented with a six-month history of intense pruritus. She developed erythematous papules on her lower extremities and buttocks. She also scratched the lesions. The lesions were aggravated after a hot bath. She was referred for further evaluation as she suspected aspergillosis.
The lymphoma was confirmed by pleural liquid fine needle aspiration. A bone marrow biopsy was performed. A malignant proliferation was found, which included medium-sized CD3+ T cells, Reed-Stenberg cells, and CD56 (a NK marker). The malignant proliferation was negative for the blastic markers TdT and CD20.
Natural killer (NK) and T-cell lymphomas are disseminated and are mostly extranodal. This group of lymphomas is closely related to the Epstein-Barr virus. It has been described in 12% of lymphoma patients.
Treatment of unclassifiable cell lymphoma must be individually tailored to the site of the lymphoma and the patient’s performance status. Treatment can include chemotherapy and ionising radiation therapy.
Pregnancy
During pregnancy, several skin eruptions may occur. Some skin changes may be physiologic adaptations, while others are inflammatory and may require management. If you are a pregnant woman who experiences itchiness, you need to be able to differentiate among the different causes.
The most common skin eruption during pregnancy is called Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP). This condition usually occurs in the third trimester of a woman’s first pregnancy, but it may occur during a later pregnancy. Usually, the lesions begin on the abdomen, but they may also spread to the buttocks and legs.
The condition is benign for the mother, but it can cause discomfort. Treatment includes topical corticosteroids and antihistamines to relieve itchiness. It may take months for the lesions to heal.
Several types of skin disease can occur during pregnancy, including pemphigoid gestationis, polymorphic eruption of pregnancy, atopic eruption of pregnancy, and folliculitis. These diseases may require treatment and can lead to foetal distress. The skin of a newborn is typically not affected by these skin eruptions, but it is important to work closely with the neonatal paediatrician during labour and delivery.
Pruritic urticarial papules of pregnancy (PUPPP) is a benign skin condition that usually occurs in the third trimester of pregnancy. The lesions are itchy and may spread to the buttocks and legs. In most cases, the lesions are harmless to the mother, but they should be evaluated and treated by a dermatologist. The lesions are treated with topical ointments and oral medications to relieve itching.
Atopic eczema of pregnancy (AEP) is a common inflammatory skin disorder that occurs during pregnancy. The lesions are characterised by a red rash and intense itching. Indirect immunofluorescence and histological studies can help distinguish AEP from other pruritic skin eruptions.
