Papulosquamous and inflammatory skin disorders: Pathology review

At the dermatology clinic, 9 month old Ethan is brought in due to recurrent skin rashes. According to his mother, he develops red, weeping lesions on his cheeks, chin, forehead, as well as the knees and elbows. His mother said these seemed to be related to the consumption of specific foods, but she couldn’t figure out what kinds. Physical exam reveals multiple erythematous papules with excoriations. Blood work shows increased IgE levels. On the same day, 68-year-old Marcia presents complaining of a pruritic rash on her wrists and elbows that has persisted for about 8 months. Her medical history is significant for chronic hepatitis C infection. On physical examination, there are multiple, flat-topped, violaceous-colored plaques, on the flexor surfaces of her upper extremities.

Based on the initial presentation, Ethan and Marcia seem to have some form of papulosquamous or inflammatory skin disorder. Okay, first, let’s talk about physiology real quick. Normally, the skin is divided into three main layers, the epidermis, dermis, and hypodermis. The hypodermis is made of fat and connective tissue that anchors the skin to the underlying muscle. Above the hypodermis is the dermis, containing hair follicles, nerve endings, glands, blood and lymph vessels. And above the dermis is the epidermis, which contains 5 layers of developing keratinocytes. Keratinocytes start their life at the lowest layer of the epidermis, so the stratum basale or basal layer. As keratinocytes in the stratum basale mature, they migrate into the next layers of the epidermis, called the stratum spinosum, stratum granulosum, stratum lucidum, and finally, the stratum corneum, which is the uppermost and thickest epidermal layer. Before we dive into the various skin disorders, there are several high yield terms to describe skin lesions. So, macules are flat, well circumcised lesions up to 1 centimeter in diameter, while patches are similar to a macule but are larger than 1 centimeter. Papules are raised bumps that are up to 1 centimeter in diameter, while plaques are like papules but larger than 1 centimeter. A smooth papule or plaque that is transient, meaning that it comes and goes, is called a wheal. Finally, scales are accumulations of thickened stratum corneum that become dry and flaky and sometimes peel off; while crusts are dry exudates like sebum, pus, or blood.

All right then, onto papulosquamous and inflammatory skin disorders! Let’s begin with atopic dermatitis, also known as eczema. This is a chronic inflammatory skin disease that’s particularly common among young children, but can last into adulthood. For your exams, remember that it can be a part of the characteristic atopic triad, which includes atopic dermatitis, allergic rhinitis and conjunctivitis, and allergic asthma. Now, the exact cause of the skin inflammation seen in atopic dermatitis is not fully agreed upon, however it seems to be a mix of dysfunction in the immune system and skin barrier abnormalities. In regards to dysfunction in the immune system, atopic dermatitis is associated with an elevated serum IgE, as well as certain foods and environmental triggers like pollen. Abnormalities of the skin barrier in atopic dermatitis are associated with a mutation in the filaggrin gene. Filaggrin is a protein that binds to keratin and contributes to the formation of the skin barrier, so if it’s abnormal, it can cause the skin barrier to become porous and leaky. This allows water to accumulate between cells, leading to edema in the epidermis, which is called spongiosis. Now, if this water escapes, it will leave the skin dry and scaly. This dry skin is extremely itchy, and that’s characteristic of atopic dermatitis. So, the rash usually presents as patches of red itchy skin that come and go, but can occasionally blister and peel. Over time, the skin can undergo lichenification, meaning that it becomes leathery and tough. Now, a high yield fact regarding the location of the rash is that in infants, it’s usually on the face and scalp. As children get older, it’s more common on flexor surfaces of extremities, like the creases of the wrists, the insides of the elbows, and the back of the knees. And in adults, it’s usually on the hands and feet. The diagnosis of atopic dermatitis through clinical examination, and lab tests might show increased eosinophils and serum IgE levels, and skin testing or allergen-specific IgE antibodies might identify the specific allergens that should be avoided. Treatment focuses on reducing symptoms by minimizing exposure to food and environmental triggers and reducing stress, as well as keeping the skin hydrated with moisturizers, minimizing itching with oral antihistamines, and dampening the immune reaction with topical medications like steroids or calcineurin inhibitors.

Next, let's look at urticaria, also called hives. Hives are a common type 1 hypersensitivity reaction characterized by edema of the dermis and dilation of the lymphatic vessels that can appear anywhere on the body. It presents with slightly raised, well-defined wheals which are usually red, blanch with pressure, and are extremely itchy. The key feature is that these lesions come and go very rapidly. Diagnosis is clinical, and since the whole thing typically resolves between 30 minutes and 24 hours, no treatment is needed. But if the itching is really bad, topical cooling moisturizers or oral antihistamines can be used. For severe cases, antihistamines and systemic steroids can be used.

Next, there’s contact dermatitis, which is a localized reaction that arises from direct skin exposure to a triggering substance, typically presenting with an itchy, erythematous papulovesicular rash, often with edema and oozing vesicles. You can have allergic contact dermatitis or irritant contact dermatitis. Allergic contact dermatitis is induced by things such as poison ivy, latex, topical antibiotics like neomycin, and metals such as nickel. Irritant contact dermatitis is caused by things such as soaps and cleansers, acids and alkalis, solvents, bleach, plants, paper, and dust or soil. Allergic contact dermatitis is due to type IV hypersensitivity reaction, where the triggering substance indirectly damages the skin by activating a T-cell mediated reaction at the site of exposure. In contrast, irritant contact dermatitis is due to physical, mechanical, or chemical irritation that directly damages the keratinocytes of the epidermal layer. Now, diagnosis of contact dermatitis is clinical, and definitive diagnosis can be made through skin patch testing. Skin biopsy is rarely needed, but in case of acute allergic contact dermatitis, it might show spongiosis, similarly to atopic dermatitis; while chronic allergic contact dermatitis is characterized by thickening of the stratum spinosum and stratum corneum. In acute irritant contact dermatitis, some degree of spongiosis might be also seen, although less pronounced than that seen in acute allergic contact dermatitis; while in chronic irritant contact dermatitis, findings are less clear. Now, the key to treatment is proper evaluation and identification of the triggering substance to avoid and remove it. For allergic contact dermatitis, topical corticosteroids can help reduce skin inflammation, while for irritant contact dermatitis, emollients and moisturizers can be used.

Moving on, seborrheic dermatitis is an inflammatory skin condition that affects areas with a high density of sebaceous glands, such as the face, scalp, and periocular region. The classic presentation of seborrheic dermatitis involves erythematous, well demarcated plaques with yellow, greasy scales. For your tests, remember that in infants, seborrheic dermatitis in the scalp is commonly referred to as “cradle cap”. Now, the cause of seborrheic dermatitis is not known, but it is believed to involve a number of genetic and environmental factors, as it tends to worsen with stress and during the cold and dry winter months. Colonization of the skin by Malassezia yeast is also believed to play a role. Additionally, it has been associated with various disorders, such as Parkinson’s disease, as well as immunodeficiency, like with HIV infection. Diagnosis is clinical, and treatment includes topical antifungal agents like shampoos or creams, and in severe cases can be combined with low potency topical corticosteroids such as hydrocortisone.