Dermatological Conditions Inducing Acute and Chronic Pain

Mathilde Hayoun-Vigouroux1 and Laurent Misery1,2

1Department of Dermatology, University Hospital of Brest and 2University of Brest, LIEN, Brest, France

Pain is a common condition in dermatology. The aim of this review is to analyse the characteristics of pain in dermatology. Some skin diseases are conventionally known to cause pain; e.g. ulcers, pyoderma gangrenosum and herpes zoster. Common dermatoses, such as psoriasis or atopic dermatitis, can also cause significant pain. Some conditions are characterized by neuropathic pain and/or pruritus, without visible primary lesions: e.g. the neurocutaneous diseases, including small fibre neuropathies. Patients often fear pain in skin surgery; however, surgical procedures are rather well tolerated and any pain is mainly due to administration of local anaesthetic. Some therapies may also be uncomfortable for the patient, such as photodynamic therapy or aesthetic procedures. Thus, pain in dermatology is common, and its aetiology and characteristics are very varied. Knowledge of the different situations that cause pain will enable dermatologists to propose suitable analgesic solutions.

Key words: pain; dermatoses; dermatology; neuropathic pain.

Accepted Apr 8, 2022; Epub ahead of print Apr 8, 2022

Acta Derm Venereol 2022; 102: adv00742.

DOI: 10.2340/actadv.v102.284

Corr: Mathilde Hayoun-Vigouroux, Department of Dermatology, Centre Hospitalier Régional Universitaire Morvan, 2 avenue Foch, FR-29200 Brest, France. E-mail: vigourouxmathilde7@gmail.com

SIGNIFICANCE

In daily practice, the dermatologist encounters many situations responsible for pain, whether it be skin disorders or some therapeutic or diagnostic procedures. This article provides an updated overview of the painful conditions in dermatology. The circumstances highlighted are intentionally frequent situations, which could be met by the greatest number of dermatologists, both in hospitals or in private practice. This review is intended to be a practical guide for dermatologists to help them to identify and analyse pain or to anticipate situations that may cause pain in their daily practice, and thus to propose an appropriate analgesic approach.

INTRODUCTION

Pain is defined by the International Association for the Study of Pain (IASP) as “an unpleasant sensory and emotional experience associated with or resembling that associated with, actual or potential tissue damage (1)”. In daily practice, the dermatologist encounters a wide variety of types of pain, ranging from acute surgical pain to chronic pain, inherent to many dermatoses, or acute pain from other skin pathologies, such as wounds (2). Pain can be chronic or acute. Chronic pain is defined by the IASP as ‘’pain without apparent biologic value that has persisted beyond the normal tissue healing time, usually taken to be 3 months”. Chronic pain results from alterations at various levels of the pain pathway (3). Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system, and nociceptive pain arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors (4).

In dermatology, pruritus is the most common cutaneous symptom, and has been widely described and analysed (5). Although pain is also a common symptom in dermatology, it has been studied less than pruritus (6). The aim of this review is to analyse the circumstances of pain in dermatology.

METHODS

This narrative review was performed after a PubMed, Cochrane, Google Scholar search of papers published since 1 January 2000, using the following terms: “pain AND dermatology”. Additional searches were performed with each identified painful situation: eczema, psoriasis, skin surgery, shingles, ulcers, pain repercussions, etc. Articles in a language other than English or French were excluded. Articles were initially selected based on the title, and then on the abstract. The full text of all potentially relevant articles was retrieved for detailed evaluation. Reference citations within identified articles were also searched for relevant evidence.

Chronic pain from certain skin disorders

A 2017 French study analysed the presence and frequency of pain by interviewing more than 1,565 patients with skin disorders (atopic dermatitis (AD), lower limb ulcers, pressure ulcer, psoriasis, sexually transmitted infections, and sensitive skin). The pain was chronic in 25.7% of patients and transitory in 74.3%. Only 59.3% of patients were specifically managed, and 22.6% had a 0–10 visual analogue scale (VAS) >7/10 (7).

Chronic ulcers of the lower limbs. The prevalence of wound-related background pain in a meta-analysis of chronic venous leg ulcers, varies from 46% to 100% (n = 1,446) (8). Ulcer care can be responsible for acute pain: in an observational study, 80% of patients with leg ulcers (n = 1,900) report moderate to severe pain during dressing changes (9). Patients who experience severe pain during dressing care are more likely to experience spontaneous pain (9). Classically, arterial ulcers are known to be very painful due to hypoxia (3). But venous ulcers are also painful and pain is even the main complaint reported by patients (10). A neuropathic component of pain seems to be frequent; a study has shown that 58% (n = 81) of patients with leg ulcers are affected (11). An ulcer persisting for more than 90 days and the presence of pain are parameters associated with the presence of depressive symptoms (12). Depression can slow down wound healing (12). Pain diminishes the quality of life: it reduces patients’ mobility and consequently reduces physical activity and leads to sleep disorders (13, 14).

Bullous diseases. There are few specific studies into pain in bullous diseases. The presence of pain is intuitively recognized, particularly during care. Concerning superficial pemphigus or pemphigus vulgaris, one study has shown that half of patients report skin pain (Table I). It did not find a correlation between pain intensity and pemphigus severity (15). For epidermolysis bullosa (EB), all patients (n = 374) with EB in the study by Fine et al. (16) reported pain on walking or standing. Pain due to recessive dystrophic EB is more severe than other subtypes (junctional EB, dominant dystrophic EB, EB simplex) (17). A study into localized EB simplex shows that all patients (n = 57) experience pain during flares of blisters or dressing changes (Table I) (18). In recessive dystrophic EB, a neuropathic component related to small fibre neuropathy has been demonstrated (19), and neuropathic component is also found in junctional EB (20) and EB simplex (18). Toxic epidermal necrolysis results in painful care, but there are no specific studies on pain characteristics (21). One study showed that one-third of patients experienced chronic pain 1 year after the reaction, no neuropathic component was found, but chronic pain in this context could be a manifestation of post-traumatic stress syndrome (Table I) (22).

Atopic dermatitis. Skin pain is an important part of AD. Pain is reported by 40–60% of patients with any severity of AD (Table I) (7, 23–25). Thyssen et al. (26) showed that the intensity of skin pain is proportional to the severity of AD. Vakharia et al. (27) also found that severe skin pain is associated with increased severity of AD (23). The most painful areas in Maarouf’s study were the excoriated areas as well as the hands, toes, and perioral region. These locations were also found in the Thyssen study, which added the thoracic region (26). The skin pain described by patients suggests a neuropathic component (7, 23–25, 28) (see Table I). The pain triggers seem to be similar to those that trigger pruritus: sweating, ambient heat, emotional stress, hot-water baths, rubbing the skin, wearing wool or synthetic clothing (27, 28). Topical calcineurin inhibitors, dermocorticoids and topical crisaborole may cause pain and burning (27, 28). Note that topical calcineurin inhibitor activates TRPV1 channels, which mediates an antipruritic effect, and can cause a burning sensation that disappears with repeated use.

Severe pain is also associated with poor sleep, depressive symptoms and poor quality of life (23). Taking pain into account is therefore important in assessing the impact of AD and to optimize its therapeutic management (28).

It has been shown that pain and pruritus coexist, while it is classically accepted that painful stimuli inhibit the itchy sensation, yet Vakharia (23) showed that 72% (n = 144) of patients link their pain to scratching and itching, and Maarouf et al. (27) showed that 78% (n = 103) of patients had itching and associated pain. Ikoma showed that nociceptive stimuli induced pruritus instead of pain in patients with AD, unlike in the healthy control group and the psoriasis group. This study raises the possibility of central pruritus sensitization mediated by C nociceptors, whereby a painful stimulus would induce pruritus instead of pain (29). However, it is not known if the pain is caused by pruritus, which leads to itching and therefore excoriation. The link between pruritus and pain in AD is therefore not yet understood. What is highlighted is that, in AD, the pain and pruritus pathways are not antagonistic, as is generally accepted.

Psoriasis. The prevalence of skin pain is important, affecting 30–50% of patients with psoriasis (see Table I) (7, 30–32). Epidemiologically, the most painful patients are women, with a low socioeducational level, chronic comorbidities and a long duration of psoriasis evolution. On the other hand, the studies are contradictory with regard to the influence of age (31, 33). Regarding the intensity of skin pain, Misery et al. (30) found a median score of 6/10 (numerical rating scale (NRS) 0–10), and Patruno et al. found a median score of 7/10 (NRS 0–10) (31). Moderate to severe joint pain concerned 69% of patients with psoriatic arthritis (n = 847) and 45% of those without (n = 3,169) (34) (see Table I). Moreover, skin pain seems to have a neuropathic component for more than half of the patients (7, 30) (see Table I). The most painful areas are the palms, plantar regions, scalp, and genital areas. The lumbosacral region is the least painful. The affected area is not necessarily correlated with the intensity of pain: palmoplantar or inverted psoriasis will be painful, even if the affected area is limited (31, 33). Patients with depression experience more severe skin pain than others, and the reverse is true: patients with skin pain present more symptoms of anxiety or depression (33, 35). Pain is a major contributor to the psychosocial impact of psoriasis, but is largely underestimated in psoriasis severity scores alone. It is not taken into account in the Psoriasis Area and Severity Index (PASI) (36, 37) and is the subject of only one question in the Dermatology Life Quality Index (DLQI) (38). Pain relief is one of the most important criteria for satisfactory treatment according to the patients, along with a reduction in pruritus, a reduction in burning sensations, and skin clearance (33, 39).

Hidradenitis suppurativa. Most patients experience lesion-linked pain in the course of hidradenitis suppurativa (HS) (40) (see Table I). Pain is one of the most debilitating symptoms of HS, it can be acute due to nodules and abscesses during outbreaks, and can become chronic in cases of advanced disease (41, 42). A neuropathic component is also possible in 30% of patients with HS (41, 42) (see Table I). The pain intensity is approximately 5/10 (40, 42) (see Table I) and is more intense than in many dermatological pathologies, such as psoriasis, eczema, acne, or skin tumours (41).

Quality of life is significantly diminished in HS, with sleep disturbances, discomfort in daily activities, discomfort in social and sexual interactions, and depression. The prevalence of depression is higher among people with HS than among those with other dermatological conditions (41).

Post-herpetic neuralgia. In patients with herpes zoster, neuropathic pain appears with a dermatomal distribution that does not cross the midline, which gives way to an erythemato-vesicular eruption (43). Post-herpetic neuralgia is defined as pain persisting for 90 days after acute onset. The risk of post-herpes zoster pain increases with age, lesion size and immunosuppression, especially among those taking anti-tumour necrosis factor (TNF)-alpha drugs (44). People over 70 years of age are at increased risk of more persistent pain (43). Post-herpetic neuralgia significantly impacts quality of life, including the ability to perform activities of daily living, and may lead to depression, chronic fatigue, and weight loss (44).

Neurocutaneous diseases. These pathologies lead to neuropathic pain and/or neuropathic pruritus of the skin due to nerve damage without primary skin lesions. There are different syndromes depending on the location and the nerve involved: e.g. scalp dysesthesia, vulvodynia, brachio-radial pruritus, paraesthetic notalgia, and paraesthetic meralgia (2, 45, 46).

In addition, this category includes small fibre neuropathies that cause autonomic symptoms and sensory symptoms (pain, pruritus, burning) that dominate the limbs in a distal-to-proximal gradient. A diminution of intraepidermal nerve fibre density, which is assessed on skin biopsies, is a major diagnostic criterion (47).

Sensitive skin syndrome. Sensitive skin is a syndrome defined by the Special Interest Group on Sensitive Skin of the International Forum for the Study of Itch (IFSI): “The occurrence of unpleasant sensations (stinging, burning, pain, pruritus, and tingling sensations) in response to stimuli that normally should not provoke such sensations. These unpleasant sensations cannot be explained by lesions attributable to any skin disease. The skin can appear normal looking or be accompanied by erythema. Sensitive skin can affect all body locations, especially the face (48)”. Cosmetics seem to be the main triggering factor of sensitive skin (49).

Acute pain induced by dermatological procedures

Surgical procedures. The consideration of acute post-operative pain is crucial. If it is neglected or underestimated there is a greater risk of complications, such as delayed healing, bleeding, insomnia, cardiovascular sequelae, and a risk of chronic pain, substance abuse and negative psychological repercussions (50).

The mean pain score during surgical procedures and biopsies, found by Talour et al. (51), is 2.2/10 (NRS 0–10), which corresponds to the pain associated with injection of the anaesthetic. The pain is rather mild to moderate in Mohs’ surgery (50); between 2.5/10 and 3.5/10 (51–53) (NRS 0–10). Although surgical procedures and biopsies are well tolerated by patients, with a local anaesthetic usually deemed appropriate, administration of the anaesthesia is painful for most patients (88.5%, n = 120). On average, this pain is evaluated at a level of 2.8/10 (VAS 0–10) (54). The pain is maximal on the day of surgery (52, 53, 55, 56), reaches its peak at 4 h, and decreases sharply 12 h after the intervention (57). Forty to 50% (n = 212 and n = 433, respectively) of patients used an analgesic postoperatively, especially on the first day, and the majority used acetaminophen (52, 55). A single dose of acetaminophen is sufficient in the majority of cases (53). The consumption of opiates varies from 7% to 20% (n = 433 and n = 212, respectively) (52, 55, 56). The most painful locations are the extremities, the axillary hollow, and the head (51, 55), and, especially on the face: the lips, the nose, ears, and forehead (58). The perineum is also a painful localization, especially for injection of an anaesthetic. In the absence of premedication by topical application, 42% (n = 18) of patients with perineal lesions prefer general anaesthesia, and this proportion is increased if the size of the lesion is large (>2 cm) (54). The sites least prone to significant postoperative pain are the trunk and limbs (51, 55).

The characteristics of the surgery, the number of anatomical sites operated on the same day or the type of closure may influence the intensity of postoperative pain, but the results are contradictory among studies (52, 55, 56).

Preoperative anxiety and “pain catastrophization” lead to higher postoperative pain scores, and anxiety plays a role in the risk of chronic postoperative pain (57, 59).

Photodynamic therapy. Pain during photodynamic therapy (PDT) is the main limiting adverse effect the use of this technique in dermatology (60). Traditional topical and oral anaesthetics are ineffective in PDT (61). No significant correlation has been found between pain during PDT and age or sex (61, 62). Lesions on the face and scalp are more painful than other body sites, and larger lesions are more painful during PDT (60, 61). Actinic keratosis is more painful than basal cell carcinoma (62). PDT using a MAL or 5-aminolevulinic acid methyl ester (METVIXIA*) photosensitizer is less painful than using ALA or 5-aminolevulinic acid (AMELUZ*) (60). Daylight PDT is less painful than conventional red light PDT, or may even be painless, but the efficiency is similar (61, 62).

In conlusion, pain in dermatology occurs in a variety of circumstances and is inherent in a large number of skin disorders. It is widely known and studied for some conditions, such as ulcers or zoster. However, pain is less recognized in certain common pathologies, such as AD or psoriasis, even though its relief is among the most important criteria according to patients. In addition, pain and itch are generally regarded as antagonistic, but they coexist in many of dermatoses, highlighting that although separate specific pathways have been identified, the mechanisms underlying pain and itch overlap.

Moderate to severe pain has a strong negative impact on quality of life. In particular, it alters the quality and quantity of sleep, interferes with activities of daily living, social interactions, school or professional performance, sexual relations, and causes depressive symptoms, etc. Therefore, pain management is important, and dermatologists must be able to propose appropriate therapies and master the main analgesic tools (Table II; (63–97)).

Conflicts of interest: H-V have no conflicts of interest to declare. LM: Galderma, Lilly, Pfizer: speaker, investigator, consultant, and Pierre Fabre: speaker, consultant.

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