Introduction

What is Nodular Acne?

Acne vulgaris (commonly known as acne) is a collection of inflammatory skin diseases affecting skin pores that range significantly in severity of symptoms. About 9% of people worldwide have acne with the most affected age group being teenagers. Inadequate treatment of acne leads to scarring that negatively affects people’s self-esteem, increasing the risk of depression, to which teenagers are especially sensitive.^1,2

Skin involvement in acne can vary from affecting skin pores only to deep skin layers. Depending on the morphology of lesions, acne can be classified into three groups: comedonal, papulopustular, and nodulocystic.³

Comedonal acne is characterised by the formation of comedones - enlarged skin pores that are filled with an excessive amount of sebum usually without inflammation. Comedones can be either open to the external environment in which case sebum oxidises and turns black (so-called ‘blackheads’); or closed comedones with sebum contents not exposed to air (‘whiteheads’).⁴

In papulopustular acne, clogged skin pores get infiltrated by skin bacteria like Propionibacterium acnes (P. acnes) that cause local inflammation and the formation of small red bumps - papules. When white blood cells in papules fighting off the invaders die off they form a pus-filled cap and papules transform into what is known as pustules. Both papules and pustules, unlike comedones, are inflamed and can be painful.⁵

Nodulocystic acne is the most severe type of acne vulgaris associated with the formation of painful lesions affecting deeper layers of the skin outside the initially affected pore - called nodules and cysts. Nodules are large bumps not filled with fluid that feel like hard knots under the skin. Cysts are filled with pus and thus feel softer than nodules.⁶

How severe is nodular acne and how important is treatment?

Compared to other types of acne, nodulocystic acne more often resolves with the formation of scars and changes in skin pigmentation. Nodulocystic lesions are also significantly more painful and attention-grabbing to surrounding people. This can seriously impact the quality of life of affected patients. A rare type of nodulocystic acne, acne conglobata, is formed from several interconnected acne lesions that are very painful and disfiguring, especially when appearing on the face.⁷ An ideal treatment plan would have to successfully clear acne lesions, prevent the recurrence of symptoms, and prevent skin scarring.⁸ 

Overview of common treatments for nodular acne

Topical Treatments

Topical treatments aim to control sebum production and bacterial growth on the skin to prevent infection of skin pores. Topical treatments usually have a greater impact on lighter forms of acne while in nodulocystic acne they should be used as an adjuvant to systemic treatment.⁹

The most common topical drugs for acne are benzoyl peroxide, topical retinoids, topical antibiotics, and chemical peels.

• Benzoyl peroxide is an aggressive oxidiser and speeds up the shedding of dead skin cells, preventing pores from plugging. Benzoyl peroxide also has antimicrobial properties against P. acnes¹⁰
• Retinoids are a large class of drugs with vitamin A-like properties. They bind to retinoid receptors inside the cell nucleus forming complexes that interact with DNA and change the expression of key genes involved with skin shedding and sebum production, causing thinning of skin and reduction in sebum levels, respectively. Some retinoids are applied on acne lesions directly as topical treatments, most notably retinol (vitamin A), adapalene, tazarotene, and tretinoin¹¹
• Topical antibiotics for the treatment of acne include clindamycin and erythromycin. Usually, topical antibiotics alone don’t have a satisfactory effect on acne and are not recommended for monotherapy. Instead, they are combined with benzoyl peroxide which increases their antimicrobial effect and prevents resistance¹²
• Chemical peels incorporate different chemical substances (mostly acids and phenol) that are applied directly on the skin and cause desquamation. Superficial peels remove only the top layer of the skin (the epidermis) and include ascorbic acid (vitamin C), glycolic acid, and salicylic acid. Medium or mid-depth peels penetrate deeper into the skin exfoliating the entire epidermis and a small part of the dermis. Examples of medium peels are highly concentrated solutions of glycolic or salicylic acid or diluted phenol solutions. Deep chemical peels use concentrated phenol that exfoliates the entire epidermis plus a large portion of the dermis¹³

Apart from topical treatments dermatologists also recommend a skin care routine comprising a washing agent, moisturiser, and sometimes bioactive substances like niacinamide. The skincare routine should be tailored to each person’s specific skin condition and type. Regular skin cleansing with an appropriate cleansing agent can help clear skin pores from excess sebum and skin debris, preventing blockages. Topical niacinamide is widely used as a daily product for controlling sebum production. Niacinamide also can help combat hyperpigmentation by inhibiting melanosomal transfer from melanocytes to developing keratinocytes in the epidermis.¹⁴

Systemic Treatments

Systemic acne treatment is more efficacious but also has more side effects due to the low selectivity of acne medications. Treatment of nodulocystic acne in most cases incorporates an oral retinoid, a hormonal medication and/or antibiotics.¹⁵

• Isotretinoin is the most commonly prescribed oral retinoid with relatively high selectivity for skin cells. Other oral retinoids include acitretin and trifarotene
• Tetracyclines are commonly prescribed as oral antibiotics for nodulocystic acne. For patients with intolerance to tetracyclines usually, macrolides such as azithromycin are preferred but should still be used as a second-line treatment due to the rising incidence of resistance to macrolides
• Hormonal medications - when the underlying cause of acne is hormonal imbalance, i.e. an abundance of androgens, hormonal therapy is usually prescribed - oral contraceptives and progesterone analogues. Oral contraceptives act by suppressing the production of androgens from ovaries, reducing sebum production and the formation of acne lesions. Oral contraceptives are sometimes combined with oral progesterone analogues like spironolactone and drospirenone due to their supplemental antiandrogenic properties

Physical Procedures

In severe acne with inadequate response to treatment, corticosteroid injections have been shown to drastically shorten the recovery time from a few weeks down to just a few days. The most commonly administered corticosteroid is triamcinolone which has a powerful anti-inflammatory effect when injected directly into acne lesions.¹⁶

Laser therapy is another physical procedure for severe types of acne. The laser beam increases the temperature of water in skin pores causing coagulation of nearby tissues and stopping sebum production.¹⁷ Laser therapy can reduce acne scarring by burning away scar tissue on top of lesions and allowing new healthy skin to form.¹⁸ When a cystic lesion doesn’t respond to medications, it can be cut open with sterile instruments and drained from excess pus to relieve symptoms and speed up regeneration.¹⁹ This procedure should be performed only by dermatological surgeons or general surgeons as inexperienced people can worsen inflammation.

Side Effects of Treatments of Topical Treatments

Irritation and Allergy

Even though topical treatments are generally safer than systemic ones, some of them can irritate the skin causing redness, tenderness, and even peeling of the skin. Irritation is more common in patients with sensitive skin, pregnant women, and people with a history of dermatitis. Some people can be allergic to topical medications and cosmetic products. The most popular allergens in skin products are parabens, which are a type of preservative. Allergic reactions of the skin present with redness, itching, swelling, and blistering.²⁰ This is why many companies nowadays incorporate non-paraben preservatives in their products and label them as ‘paraben-free’. Patients with acne should have a good understanding of the products their skin is intolerant to. 

Resistance to treatments

Topical antibiotics are the biggest concern for resistance to acne treatments. They are usually used for long periods - up to 2 months. Bacteria that are constantly exposed to low doses of antibiotics in topical products can develop resistance. For this reason, topical antibiotics are co-formulated with benzoyl peroxide to increase their antibacterial effects and lower the risk of resistance.²¹

Side effects of phenol chemical peels

Although being a topical treatment, phenol peels can have a very aggressive effect on the body and only be considered with people with severe acne as it practically scrapes a person’s face off. Phenol has significant renal toxicity and can cause life-threatening arrhythmias and hypotension. Cardiac function should be constantly monitored and intravenous fluids should be given before and during the procedure to facilitate phenol excretion and minimise renal damage.²²

Side effects of systemic treatments

Systemic Antibiotics

Tetracyclines are contraindicated in pregnant women and children under the age of 8 due to binding calcium in the developing skeleton, disrupting normal bone growth in the fetus and growing children, respectively. Tetracyclines also build up inside teeth and cause discolouration and weakening of enamel, making teeth more prone to the formation of cavities. Tetracyclines also distribute into the skin and absorb UV light causing damage to surrounding tissues, making the skin more sensitive to light. Patients should avoid taking oral tetracyclines with dairy foods and mineral supplements that decrease drug absorption.²³

Macrolides are generally considered a safer treatment option when tetracyclines are not recommended, including in children and pregnant women. Common side effects of macrolides are diarrhoea, abdominal pain, and nausea caused by direct stimulation of motilin receptors in the gut resulting in increased peristalsis. Macrolides may potentially cause prolongation of the QT interval increasing the risk of a potentially fatal arrhythmia known as Torsades de Pointes.²⁴

Hormonal Treatments 

Birth control pills are associated with a greater risk of headaches, changes in mood and libido, abnormal menstrual bleeding, weight gain, and breast tenderness.²⁵ They should be avoided in patients at high risk of hormone-dependent cancers.²⁶ Taking estrogens increases the risk of blood clots, especially in postmenopausal women and smokers.²⁷ Higher doses of estrogens have a greater risk of side effects making low-dose birth control the more preferred option for long-term treatment.

Systemic Retinoids

• Dermatological - retinoids reduce sebum production from oil glands and cause dry skin and peeling, especially on the nose and around the lips. This is a common side effect that typically lasts for a few weeks until the skin builds tolerance. Retinoids also make the skin more sensitive to light and sunburns. Patients on systemic retinoids should use sunscreen with a high SPF daily
• Mucosal-retinoids may cause drying of the mouth, nose, and eyes. Patients may need to use artificial tears for dry eyes to prevent irritation
• Gastrointestinal and hepatic-retinoids may cause elevations in liver enzymes but they usually are asymptomatic and transient.²⁸ In rare cases retinoids have been linked to serious cases of inflammatory bowel disease²⁹
• Psychological - retinoids increase the risk of depression and suicidal ideation. Dermatologists should be vigilant of this potential side effect and work closely with psychiatrists to manage mental health concerns in patients³⁰
• Pregnancy risk - retinoids can cause severe birth defects when taken during pregnancy. Pregnant women taking retinoids should also use reliable contraception. This disclaimer is usually present on the labels of retinoid products. Isotretinoin should usually be discontinued 1 month before getting pregnant³¹

Side effects of physical procedures

Corticosteroid Injections

Corticosteroids have immunosuppressive properties and may increase the risk of skin infections.³² They also suppress skin healing and might prolong the post-procedural regeneration period. Skin atrophy and thinning, hypopigmentation and scarring are also associated with steroid injections.³³ Corticosteroids also cause abnormal dilation of capillaries in skin capillaries - telangiectasia.³⁴

Laser Therapy

Laser therapy can cause burns, changes in skin texture, and hypopigmentation. Changes in skin pigmentation are more evident in people of colour.³⁵ The skin is often inflamed for a certain period after laser therapy and patients may feel pain, burning or itching in the treated area.

Drainage

Drainage procedures often leave visible scars on the skin. Healing lesions are a potential window for new infections. Taking antibiotics after draining acne lesions may improve the outcomes of the procedure.

Summary

Acne treatments should be patient-specific and tailored to each patient’s condition and skin type. Before starting treatment, the dermatologist should carefully assess the disease severity, the risk of complications, and expected outcomes. The effects of acne treatments can take a while until they become visible so healthcare professionals should regularly monitor treatment progress and encourage patients to adhere to the prescribed regimen and make meaningful changes to their lifestyle. The benefit of treatment should always be weighed against the potential safety risks and the latter should never be underestimated.