Management of Psychiatric Disorders with HIV and Dermatological Disorders.

PSYCHIATRIC ASPECTS OF HIV

Introduction

Human immunodeficiency virus (HIV) infection is transmitted through sexual contact, blood, and through vertical transmission from mother to child during pregnancy or during breastfeeding. The immune deficiency results from decrease in CD4+ T cells as well as dysregulation of antibody production by B cells. The stages of infection include acute infection, asymptomatic infection and acquired immunodeficiency syndrome (AIDS).

The relationship between HIV infection and psychiatric conditions is bidirectional. Those with psychiatric disorders like depression are more prone to contracting AIDS due to risky behavior including substance abuse. Similarly, those infected by HIV are more prone to develop psychiatric problems including depression and neurocognitive disorders. An Indian study found the lifetime prevalence of any psychiatric illness in persons with HIV to be 45%.[1] The common psychiatric and neurocognitive conditions associated with HIV along with their reported prevalence are enumerated in Table 1.[2]

Table 1

Psychiatric and neurocognitive conditions associated with HIV

Psychiatric Disorder	Percentage
Depression	5.8-36
Substance Abuse	7-58.3
Anxiety	4.3-44.4
Psychosis	6-17
Adjustment Disorder	3.8-67.6
Bipolar Disorder	1.5
HIV-associated Neurocognitive Disorders	43.9
	(ANI 26.2, MND 8.5, HAD 2.1)
Delirium	30-40

Depression

Depression is the commonest psychiatric condition associated with HIV. The relation between HIV and depression is complex; depressed individuals may resort to risky behaviors like intravenous (IV) drug abuse which may predispose them to contract and transmit HIV. Depression is commoner in LGBTQ individuals and IV drug users who are more prone to contracting HIV. An individual who develops HIV may develop syndromal depression due to multiple reasons as mentioned in Box 1.[3] Depression needs to be identified and treated promptly because it may interfere with adherence to HIV treatment. It also increases the risk of suicidal behavior. About 10% of HIV positive individuals die by suicide and about 20% resort to self-harm.[3] One Indian study reported 40% prevalence of depression among HIV-positive patients out of which 14% harbored suicidal ideas.[1]

Assessment and management

Depression poses a diagnostic challenge in patients with HIV as it often presents with multiple somatic complaints rather than classical cognitive symptoms. Patient Health Questionnaire 9 is a useful screening tool for depression in these individuals. Major depressive disorder (MDD) must be differentiated from normal sadness, delirium, substance intoxication or withdrawal, opportunistic CNS infection (cryptococcal meningitis and toxoplasmosis) and dementia. Effect of drugs as mentioned in Box 1 needs to be ruled out.

Box 1

Causes of depression in HIV

• Chronic and life-threatening nature of the illness

• HIV directly affects the subcortical structures that affect mood

• Stigma and social isolation following the diagnosis

• Antiretroviral and related drugs used in the treatment of HIV and its complications can cause depression- efavirenz, interferon, interleukin 2, steroids, zidovudine and vinblastine

• Depression can be caused by opportunistic infections following HIV

• Association with disease progression and depressive symptoms

• Depression may occur in the earlier stages of HIV associated dementia

• Elevated plasma pro-inflammatory cytokines

Once the diagnosis of depression is confirmed, it needs to be treated promptly. Both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been found to be effective in treating depression associated with HIV. However, SSRIs are considered first in line due to relatively better side effect profile. Fluoxetine, paroxetine and sertraline have been found to be effective in open label trials. Fluoxetine has also been found effective in a double-blind placebo-controlled study. Fluoxetine, paroxetine and sertraline have significant drug interactions with protease inhibitors and ritonavir. Hence, these agents should be used together with caution. Escitalopram and citalopram stand out as the safest SSRIs in terms of interaction with antiretrovirals. Testosterone has been found effective in treatment of depression in HIV patients with low testosterone levels. Stimulants like methylphenidate have also been found to be effective in treating depression, especially in those with overlapping symptoms of fatigue. Overall, treatment of HIV with antiretroviral regimen has also been found to improve depression to some extent. While using psychotropics on patients receiving retroviral medications, the drug interactions between retroviral medications and psychotropics [Table 2].

Table 2

Classification of psychocutaneous disorders proposed by Koo and Lee[13]

Types of psychocutaneous disorders	Basis of symptoms production	Examples
Psychophysiologic disorders	Dermatological disorders which often flare up during periods of stress	Alopecia areata, atopic dermatitis, acne, psoriasis, psychogenic purpura, rosacea, seborrheic dermatitis, urticaria
Primary psychocutaneous disorders	Psychiatric disorders are the root of developing dermatological conditions	Skin picking disorder, trichotillomania, delusional parasitosis, body dysmorphic disorder, factitious dermatitis
Secondary psychocutaneous disorders	Patients develop psychological problems from chronic skin disease or disfigurement	Alopecia areata, cystic acne, hemangioma, psoriasis, vitiligo, ichthyosis, Kaposi’s sarcoma

HIV-associated neurocognitive disorder

HIV-associated neurocognitive disorder (HAND) is a term which describes the complete range of neurocognitive disorders caused by HIV from asymptomatic neurocognitive impairment to HIV associated dementia (HAD).[4] Although the specific symptoms vary from person to person, the entire cluster of symptoms are often described under the umbrella term of “AIDS Dementia Complex” (ADC). ADC typically occurs when CD4 cells count falls to less than 200 cells/ml. According to the Frascati criteria [Box 2], HAND is classified into three categories based on degree of impairment: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD).[4] The broad outlines of the Frascati criteria are mentioned in Box 2. The prevalence of HAND and its subtypes has been mentioned in Table 1. In an Indian study, among patients with advanced HIV, 56% were found to meet the criterion for impairment in two cognitive domains.[5] In another Indian study which examined neurocognitive deficits in early stages of HIV, seropositive patients performed poorly in digit symbol substitution test, trail making test, and controlled word association test in comparison to normal controls.[6]

Box 2

Frascati Criteria[4]

• Asymptomatic neurocognitive impairment: Acquired impairment in cognitive functioning involving at least two of the following domains: Verbal/language; attention/working memory; abstraction/executive; memory (learning; recall); speed of information processing; sensory-perceptual, motor skills. There is no interference with day-to-day functioning and the criteria for delirium or dementia are not met.

• Mild neurocognitive disorder: Acquired impairment in cognitive functioning involving at least two domains as above. In addition, there is mild interference with everyday functioning (e.g., inefficiency at work, impaired social functioning). The criteria for dementia and delirium are not met.

• Dementia: Marked acquired impairment (2 SD below norms) in cognitive functioning involving at least two domains as above leading to marked interference with day-to-day functioning (work, home life, social activities). The criteria for delirium are not fulfilled.

• Note: There should be no evidence of any pre-existing cause in any of the above conditions

Early signs of HAND include deficits in psychomotor function (e.g., slowing of movements, gait coordination difficulties), impaired working memory, and mental flexibility. Episodic memory, particularly prospective memory, is most commonly affected. Language is often well preserved. Montreal Cognitive Assessment instrument can be used to assess cognitive deficits in HIV patients. A score of less than 26 necessitates referral for detailed neuropsychological evaluation. The Modified HIV Dementia Scale has been shown as a reliable and valid instrument for serial assessment of cognitive functions in HIV patients. Risk factors commonly associated with HAD are female sex, being elderly, higher HIV viral titers, lower socioeconomic group, substance abuse, and iron-deficiency anemia.[7]

Well-planned and optimized Highly Active Antiretroviral Therapy (HAART) regimen is the best possible method of managing HAND and lowering the risk of progression to HAD. There is no clear-cut evidence regarding the superiority of agents with greater CNS penetration like abacavir. Stimulant medications like methylphenidate have shown benefit in some studies and no improvement in others. Physical activity may be an important measure for reducing HAND.[8]

Substance misuse

High prevalence of substance misuse (7.0%–58.3%) has been found in HIV-positive patients. An Indian study reported the prevalence of substance dependence in HIV to be 10%. Substance abuse has been associated with poor adherence to antiretroviral treatment along with depression which further worsens the prognosis. The diagnosis of HIV often drives a person to substance abuse due to emotional issues and at the same time, intravenous drug use increases the risk of HIV. Opioid is commonly prescribed to persons with HIV, but their illicit use is also common. Oral buprenorphine is commonly prescribed to HIV patients but they often use intravenous buprenorphine illicitly. Substance abuse of all types along with any other psychiatric comorbidity must be aggressively treated because it affects long-term adherence to HAART and overall outcome in persons with HIV.

Anxiety disorders

HIV-positive patients report high levels of anxiety symptoms (4.3%–44.4%) [Table 1]. An Indian study found anxiety symptoms in 36% of HIV-positive individuals. A diagnosis of HIV commonly triggers anxiety because the individual perceives this as a condition with no cure. The anxiety begins even before the HIV test results are known. It persists afterwards even if the result is negative. Receiving notification of HIV-seropositive status can be a traumatic experience; it often leads to Post-Traumatic Stress Disorder (PTSD) and suicide ideation. Anxiety can be a reaction to many stressful events that emerge during the course of HIV disease. Stress can be caused just after knowing one’s HIV-positive status, side effects arising out of treatment, and adjustment to a completely new way of life. Stigma and fear of social isolation make HIV-positive individuals more vulnerable to anxiety.

Among the anxiety disorders, generalized anxiety disorder (GAD) is the commonest. An Indian study found the prevalence of GAD in HIV-positive individuals to be 12%. Just like depression, anxiety can adversely affect adherence to medication. It also leads to substance misuse. Anxiety regarding death due to the illness (death anxiety) is also common.

Among the treatment modalities, both pharmacological and psychosocial modalities have been found to be effective. Cognitive behavioral therapy (CBT) and cognitive behavioral stress management (CBSM) have been found to be effective. SSRIs, mainly fluoxetine, paroxetine and sertraline have been found to be effective in treating symptoms of anxiety in people with HIV.[9]

Adjustment disorders

Adjustment disorder affects around 30% of individuals with HIV. Adjustment disorder can be with depressive or anxiety reaction or a combination of both. It occurs commonly at the time of diagnosis of HIV. Worsening of the medical disorders during the course of the illness may also give rise to adjustment disorders. Treatment of adjustment disorder is primarily based on cognitive-behavioral or supportive psychotherapy. Antidepressants, mainly SSRIs, may also be used for short term.

Psychosis

Psychosis of newer onset is found among 6%–17% of HIV-affected individuals. Delusions occur more commonly than hallucinations. Impairment of attention and concentration, and poverty of speech are also found in first episode psychosis in HIV patients. Psychosis occurs most commonly in patients with advanced HIV infection and severe immunosuppression.[10] Psychosis increases mortality in HIV patients. Hence, early treatment is necessary. Risperidone has been found to be effective with minimal side effects in HIV patients with psychosis. One must be cautious about drug interactions with antiretrovirals. Risperidone, quetiapine and aripiprazole levels may be increased during concomitant administration with ritonavir and protease inhibitors due to inhibition of metabolism of CYP3A4 and CYP2D6. Efavirenz, nevirapine and zidovudine are known to cause psychosis-like manifestations as adverse effects.

Bipolar disorder

Reported prevalence of bipolar disorder in HIV-positive individuals is 1.5%. Patients with bipolar mania may be at higher risk for HIV infection because of impulsivity, high-risk behavior like multiple unprotected sexual acts or intravenous drug abuse. Mania in later part of HIV infection may be associated with HAD.[11] Mania may also result from side effects of antiretroviral medications such as zidovudine and lamivudine, direct effects of HIV infection on the CNS, CNS opportunistic infections (e.g., toxoplasmosis, cryptococcal meningitis) and CNS tumors like non-Hodgkin’s lymphoma. Manic episodes in HIV patients should be treated promptly to reduce the chances of spread to other people due to their high libido and poor judgment. Sodium valproate is the preferred mood stabilizer for treating mania in HIV patients. Liver function has to be monitored periodically. Lithium should be avoided because of chances of developing toxicity following HIV nephropathy. Likewise, carbamazepine is contraindicated because of increased chances of developing pancytopenia.

Personality traits and disorders

Patients with HIV have high prevalence of personality disorders. Compared to a general population rate of 10%, the prevalence in HIV-infected individuals is 19%–36% and HIV at risk individuals is 15%–20%.[12] The commonest type of personality encountered in these individuals is antisocial personality disorder and the risk of substance abuse and high risk sexual behavior is significantly greater in this population. However, it is more convenient to assess the personality of HIV-positive individuals along the dimensions of stable–unstable and introvert–extrovert, not only to reduce stigma but also for the purpose of clinical utility.[12] Unstable extroverts are the types which are most likely to engage in high-risk behaviors frequently, leading to HIV infection and subsequent spread to others. They are the ones who are less likely to adhere to treatment and stick to advice of the clinician. Zuckerman–Kuhlman Personality Questionnaire (ZKPQ) and NEO Five-Factor Inventory (FFI) are some of the instruments which may be useful in assessing personality in these groups of patients. Some of the effective techniques in dealing with these individuals include focusing on thoughts and not emotions, behavioral contract, emphasizing constructive rewards, using relapse prevention techniques, and coordinating with medical care services.

Delirium

Delirium occurs in approximately 30% to 40% of hospitalized AIDS patients.[2] Delirium in HIV patients is characterized by disturbance of attention and awareness along with disturbance in cognition which develops over a short period of time and tends to fluctuate in severity during the day. Patients with HAD and in advanced stages of HIV have the highest risk for developing delirium. Other general risk factors include advanced age, polypharmacy, and medical problems. The mainstay of management is finding out the cause and correcting it. Previously, common causes of delirium included atypical CNS and systemic bacterial infection with Cytomegalovirus, Mycobacterium avium, fungal infections, and hypoxia with Pneumocystis carinii pneumonia. With the widespread use of HAART, delirium is more commonly associated with polypharmacy, HIV-related cerebrovascular disease, and psychoactive drug withdrawal or intoxication.

Delirium Rating Scale and the Memorial Delirium Assessment Scale are the preferred assessment tools. Delirium in HIV/AIDS is managed by trying to find out the underlying cause and correcting it. Then attempt is made to reorient the patient through environmental cues. Pharmacotherapy may be initiated for symptomatic relief. The most favored antipsychotic has been low-dose haloperidol. Among the second-generation antipsychotics risperidone, quetiapine, and olanzapine are effective in resolving delirium symptoms.

PSYCHIATRIC MANAGEMENT OF DERMATOLOGICAL DISORDERS (PSYCHOCUTANEOUS DISORDERS/PSYCHODERMATOLOGICAL DISORDERS)

Disorders of the brain and skin are closely linked to one another. Disorders of skin leading to change in looks and disfigurement can lead to various emotional problems. Similarly, various psychiatric issues can have dermatological signatures in the form of visible injuries or lesions. About 30% to 40% of patients seeking dermatology consultation have an underlying psychiatric issue.

Classification

The most widely accepted classification of psychocutaneous disorders is the one proposed by Koo and Lee[13] [Table 3]. They categorized these disorders into mainly 3 types: (1) psychophysiologic disorders, (2) primary psychocutaneous disorders, and (3) secondary psychocutaneous disorders.[13]

Table 3

Interaction between Psychotropic and Antiretroviral Drugs

Fluoxetine	Level increased by protease inhibitors, decreased by nevirapine
Paroxetine	Level decreased by ritonavir, paroxetine increases ritonavir levels
Sertraline	Level increased by protease inhibitors, decreased by nevirapine
TCAs	Level increased by protease inhibitors
Venlafaxine	Level increased by protease inhibitors
Aripiprazole	Levels increased by protease inhibitors
Clozapine	Increased risk of myelosuppression with Zidovudine
Quetiapine	Levels increased by protease inhibitors
All antipsychotics	Increased QTc prolongation with ritonavir, saquinavir

The classification also includes “cutaneous sensory disorders” which includes unpleasant skin sensations with no known dermatological cause but probable psychiatric etiology. Another category mentions psychotropic medications which may be helpful for management of dermatological conditions. For example, doxepin may be more helpful than standard dermatological agents for management of pruritus.

Recent Classification of Psychodermatological Disorders[14]

Group A, Primary Psychodermatological Disease: Here, the primary dermatological disorders have a psychological mechanism, a psychological stress, and/or psychopathology as main elements in terms of either for induction or for worsening of the same. For example: psoriasis, alopecia areata, vitiligo, atopic dermatitis, chronic spontaneous urticaria.

Group B, Primary Psychodermatological Illness: In this group of dermatological conditions, there are skin symptoms, either with or without secondary self-induced skin lesions (such as excoriations), in the absence of a primary dermatosis. For example: Psychogenic pruritus, delusional infestation, self-inflicted skin lesions, body dysmorphic disorder, dysesthesias like burning mouth syndrome, vulvodynia.

Group C, Secondary Psychodermatological Disorder: In this group, psychiatric complications of medications prescribed in dermatology and dermatological consequences of psychotropics are included:

Secondary dermatologic disease related to psychiatric medications [Tables 4 and 5]

Table 4

Dermatologically Adverse Effects of Psychotropic Medications

Drug	Adverse Effects
Lithium	Hair loss, scleroderma, vasculitis, acne, psoriasis
Valproic acid	Hair loss, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema
Lamotrigine	Pruritic rash, hair loss, S-J syndrome, hypersensitivity reaction
Carbamazepine	Pruritic rash, S-J syndrome, hypersensitivity reaction
SSRIs	Allergic reaction (hives, urticaria), excessive sweating, pruritus; hair loss reported with fluoxetine
Venlafaxine	Erythroderma, erythema nodosum
TCAs	Photosensitivity, erythroderma
Phenothiazine	Erythema multiforme, S-J syndrome, drug hypersensitivity
Clozapine	Erythema multiforme, erythroderma
Alprazolam	Photosensitivity

Table 5

Severe Cutaneous Adverse Drug Reactions with Psychotropics

SJS/TEN	AGEP	DRESS
Carbamazepine, valproate, lamotrigine, anxiolytics, alprazolam	Carbamazepine, valproate, lamotrigine,	Carbamazepine, valproate, lamotrigine, olanzapine
Occurs in 4-28 days	Occurs in 1-11 days	Occurs in 2-6 weeks
Erythema, macular papules, urticaria, purpura or target rash, loose blisters that can fuse into bullae, causing skin epidermis to peel off	Joint, face, rash. Mainly aseptic pustule, less mucosal involvement, body temperature often >38 ?	Measles-like rash with small pustules. In severe cases, erythroderma with extensive exfoliation of the skin, fever, enlarged lymph nodes
Death rate 25%	Death rate 5%	Death rate 10%

AGEP – Acute generalized exanthematous pustulosis, SJS/TEN – Stevens–Johnson syndrome and toxic epidermal necrolysis, DRESS – Drug reactions with eosinophilia and systemic symptoms

Secondary psychiatric illness related to dermatologic medications. Common examples:

Depersonalization: minocycline

Mood disorders: isotretinoin; methotrexate; systemic steroids

Psychoses: dapsone; hydroxychloroquine

Sedation and drowsiness: antihistamines

Basic outlines of psychiatric assessment of dermatological patient

The basic approach to interviewing a patient referred from dermatology should follow some of the basic techniques as outlined in Box 3.[15] For patients requiring psychodermatological evaluation, a liaison clinic comprising of a psychiatrist, a dermatologist, and a clinical psychologist is the most preferred set up. This is followed in Kasturba Medical College, Manipal in India.[16] However, due to dearth of specialists, such a composite set up may not be possible across the country.

Box 3

Basic Techniques for Psychiatric Assessment of Dermatological Patient

• The patient is asked to present the main reasons for the consultation. He should also mention what are his expectations from treatment.

• The sequence of evolution of all symptoms should be outlined, including psychiatric problems

• The fluctuation of psychiatric symptoms with remission and exacerbation of dermatological lesions should be specifically probed

• Each psychiatric symptom should be assessed qualitatively- depression, anxiety, worry, obsession

• Depression and suicide risk should always be explored

Stressful life events as well as chronic stressors must be probed

• Attitude of self and others towards illness, especially stigma, should be explored

• Secondary gain if any

• Personality disorders

1. Psychophysiological Disorders

Psychophysiological disorders are those dermatological conditions where psychological issues have a major influence in the course of the disorder. Stressful life events often cause flare ups of skin lesions. As many as 50% patients with acne and almost 100% patients with hyperhidrosis report emotional triggers.[17] An Indian study reported stressful life events in 26% of patients with psoriasis vulgaris and 16% of patients with chronic urticaria within one year preceding onset or exacerbation of the skin conditions.[18]

Excessive workload, failure or poor performance in exam/interview, job loss, separation, break up of romantic relationship, or any kind of stress, anxiety, or other psychological issues generally precipitate or exaggerate dermatological disorders like psoriasis, atopic dermatitis, acne, and hyperhidrosis.

Management

Identification of the stress factors is of utmost importance for controlling these psychophysiological disorders.

Stress management by lifestyle modification like time management, adequate sleep, balanced or healthy diet, yoga, meditation, deep breathing, deep muscle relaxation or other way of relaxation might help in managing stress and increase resilience.

Pharmacological management with SSRIs and short course of benzodiazepines has been beneficial when only non-pharmacological management is not helpful.

2. Primary Psychiatric Disorders

This is the most important area where a psychiatrist plays a primary role in the management of psychocutaneous disorders. In this category, the core problem is in the psyche or brain which leads to dermatological disorders like skin picking disorder or any other body focus repetitive behaviors, delusional parasitosis, body dysmorphic disorder, etc. A few important primary psychocutaneous disorders are:

2.1. Body-focused repetitive behaviors (BFRBs)

These are repetitive behaviors directed at the body in which the patient is unable to control the act despite negative consequences. The salient features are:

Repetitive self-grooming behavior like pulling, picking-scraping or biting own hair, skin, or nails

Causes damage to the body area

Multiple attempts to stop or decrease the behavior but failed

Causes significant distress or impairment of functioning

Disorder is not due to intake of substance or any other medical, dermatological, or psychiatric disorders

Different conditions come under this umbrella term, as follows:

Hair pulling disorder (HPD) – Trichotillomania

Skin picking disorder (SPD) – Dermatillomania/Skin excoriation

Nail biting (onychophagia)/nail picking (onychotillomania)

Tongue chewing

Lip biting/cheek biting

Nose picking

Epidemiology

Although large-scale epidemiological studies are lacking, there are a few small-scale studies of skin picking disorder and trichotillomania. It has been seen that about 3% of general populations have any kind of BFRBs. Although in childhood both girls and boys are equally affected, in adolescence and adulthood, women are affected much more than men (6 to 9:1).[19]

Phenomenologically where do they fit in psychiatry?

BFRBs have many features that may match with many psychiatric disorders. Although DSM-5 describes skin picking disorder (SPD) and hair pulling disorder (HPD) as obsessive-compulsive disorders (OCD) and related disorders, there is still debate whether they are related to OCD or they fit into an independent category. ICD 11 has categorized these cluster of conditions as a separate category of BFRBs.

Interdisciplinary approach (dermatologist–psychiatrist liaison) is the key in managing this type of conditions.

Diagnosis should be done after exclusion of other similar disorders.

As comorbidities are very high, psychiatrist should address the comorbidities like depression, anxiety, personality disorders for maximum benefits and reduction of relapse.

BFRBs do not respond easily to treatment.

Psychological therapy

Habit reversal training (HRT) and stimulus control are psychological treatment methods of choice for this group of disorders.

Habit Reversal Therapy (HRT): Primary treatment for HPD and other BFRBs. Here people learn how to recognize situations where they are likely to pull their hair and how to substitute other behaviors instead.

Components in HRT: Relaxation training is also an integral part of HRT.

Awareness training/self-monitoring: In the first two to three sessions, the person learns to recognize triggers and premonitory symptoms.

Competence behavior: Replace pulling, picking behavior with other adaptive behavior like, clenching the fists to help stop the urge or redirect one’s hand from their hair to the ears in HPD or squeezing a rubber ball in case of SPD.

Generalization of behavior: Practicing new learned skills in different situations.

Stimulus Control: Modify the environment to reduce opportunities to pull or pick. Generally, persons do the act while alone so they are advised to keep the door open while doing work; persons can also cover their scalp with scarf, cap and wear gloves, or strapping fingers so that they become unable to pull or pick.

Cognitive restructuring: Cognitive therapy helps to identify and examine distorted beliefs people may have in relation to hair pulling and skin picking, and replace those maladaptive thoughts with adaptive thoughts.

Acceptance and Commitment Therapy (ACT): This helps to accept one’s urges without acting on them. It is usually used as an adjunct to HRT/stimulus control.

Drug treatment: Several medications have been tried and have shown significant results in HPD and SPD. The following medications can be used:

N-acetyl cysteine (NAC), a glutamate modulator, has shown promising results for treatment of both HPD and SPD. N-acetylcysteine promotes the body’s production of glutathione, a critical antioxidant, and thus plays a significant role in countering cellular inflammation. Based on evidences a trial of 1200–2400 mg/day for at least three months is recommended as it is safe, well tolerated and effective in all severity levels.

SSRI/Clomipramine- SSRIs are considered first-line treatment in BFRB though meta-analyses have not revealed significant benefits. Like OCD, the dose should be started low and go up to the higher therapeutic range. Clomipramine has been found to be effective in BFRBs specially in HPD.

Atypical Antipsychotics: Olanzapine has been found to be effective in a meta-analysis of HPD treatments. Other antipsychotic agents, including haloperidol, risperidone, and aripiprazole have also shown some benefit in uncontrolled studies.

Naltrexone (opioid antagonist: 50 mg/day): Naltrexone reduces urges to engage in pleasurable behaviors. It is best for patients reporting strong urges to pull.

Lamotrigine - It has been found to be effective in HPD and SPD in open label studies.

2.2. Delusional Parasitosis (DP)

In delusional parasitosis, patients have a false, firm belief that they have been infested with parasites. It is also known as delusional infestation or Ekbom syndrome.

DP occurs as a single somatic delusion with no impairment of thought processes. Patients often complain of a sensation of bugs crawling on or inside the skin. Some even bring pieces of hair, skin or cloth in a matchbox as proof of the existence of the parasites. This has been named as “matchbox sign”. Patients may try to get rid of the parasites by using needles, fingernails and this often leads to bruises and excoriations.

DP can be classified into primary, secondary, and organic forms. In primary DP, the patient has the delusion of being infested with parasites without any other psychiatric or organic disorders. Secondary DP occurs secondary to other psychiatric disorders like schizophrenia, severe depression with psychotic symptoms and dementia. Organic DP occurs secondary to general medical conditions like hypothyroidism, anemia, vitamin B12 deficiency, hepatitis, diabetes, and HIV.

Treatment

Treatment strategies include pharmacotherapy as well as psychotherapeutic methods.

A good doctor–patient therapeutic relationship is key to effective treatment. Patient’s belief should not be challenged in the initial encounter.

Atypical antipsychotics (risperidone, olanzapine, amisulpride) are now recommended due to better response and a favorable side-effect profile than first generation antipsychotics. Pimozide, which was classically used, has fallen out of favor due to cardiac side effects.

2.3 Body Dysmorphic Disorder (BDD)

Prior to DSM-5, BDD had been categorized under somatoform disorder, but now, in DSM-5, it is included in OCRD group. Here the individual is preoccupied with one or more perceived defects or flaws in his or her physical appearance which the individual believes looks ugly, unattractive, abnormal or deformed. The defect does not seem to be a matter of concern for others. The individual usually performs repetitive behaviors like checking, grooming or reassurance-seeking in response to concerns with appearance. BDD is associated with social anxiety, avoidance, depressed mood, perfectionism, and low self-esteem. It can even lead to suicidality, especially in adolescents.[20]

The most common age of onset of BDD is ages 12–13 years with equal gender distribution. Most of the individuals consult dermatologists, cosmetic surgeons, or maxillofacial surgeons to correct perceived defects in their appearance. Such interventions do not lead to improvement and often contribute to poorer outcome.

BDD is chronic, but responds favorably to treatment. However, initiating treatment may be difficult as people with BDD may not believe that their excessive fixation on perceived flaws is a psychological disorder. An empathic understanding and establishment of a good therapeutic relationship is crucial in managing BDD.

CBT is effective for treating BDD. The main step is cognitive restructuring by challenging irrational beliefs and perceptions regarding body features.

SSRIs are the drug of choice in BDD. Clomipramine is another drug which has shown good results.

SSRI combined with CBT produces favorable treatment outcomes.

2.4 Psychogenic Pruritus

In this disorder, stress precipitates episodes of itching. Itching is often triggered by emotional cues; sometimes there is nocturnal variation as well. There is localized or generalized chronic pruritus for more than six weeks in the absence of an obvious somatic cause. Emotional stress causes itching, the patient scratches the affected area to obtain relief, and further itch follows leading to a vicious cycle. Stress leads to release of histamine and other mediators of inflammation and also lowers “itch threshold”. Psychogenic pruritus often occurs in cases of depression, anxiety disorders, and alcohol abuse.

SSRIs and anxiolytics may help in reducing psychogenic pruritus. Habit reversal training is also effective in these patients.

2.5 Eating Disorders

Skin changes associated with eating disorders include gingivitis, lanugo hair, hyperpigmentation, cheilitis, melasma, and brittle nails and hair, among many others. The skin changes become more prominent when Body Mass Index (BMI) becomes very low (usually less than 16 kg/m2). CBT and antidepressants are the main treatment modalities.

2.6 Dermatitis artefacta (DA)

It is a kind of factitious disorder produced consciously by an individual to get attention from family members and physician. Common in women (female to male ratio is 3 to 5:1). Onset is in adolescent and early adulthood. Childhood trauma, abuse, dysfunctional family, borderline personality are some associated factors. It is most commonly found in upper limbs, face and then other accessible areas. Pattern of lesions are dependent on the type of objects used and mechanism of injury and can include excoriations, superficial erosions, ulcers, abrasions, blisters, ecchymosis, purpura, erythema, edema, or signs of trauma and burns. Patients also may have multiple types of concurrent lesions and different stages of healing.

When DA is highly suspected, it is important to avoid unnecessary lengthy, time consuming, and costly tests, and better to focus on resolving the more probable underlying psychiatric issues. Initially, direct confrontation with the patient regarding mechanism of symptoms production and diagnosis is discouraged, as the patient may deny and will be lost for follow-up. A strong rapport with the patient is essential and it will take time to establish a therapeutic relationship. Underlying psychological issues need to be identified and gradual disclosure about the cause of this problem to the patient and family member need to be done. History of trauma, family issues, depression, anxiety, cluster B personality are common in these patients. Treatment should be personalized. No large studies about pharmacological management are available. A few case reports showed that SSRIs have some beneficial effects.

2.7 Dermatitis Para Artefacta Syndrome

In this condition, the patient seems to have lost control over manipulation of the skin. A minimal primary lesion is often characteristically excessively traumatized, leading to pronounced, serious clinical findings. Most common underlying psychiatric condition is impulse control disorder.

2.8 Gardner–Diamond syndrome (painful ecchymoses syndrome, psychogenic purpura, and painful bruising syndrome)

Usually seen in young women, it is characterized by periodically occurring painful infiltrated blue patches, multiple physical complaints, and characteristic psychiatric symptoms.

Clinical features: The condition starts with itching, tension, or burning pain, commonly in the legs. Then erythematous plaques develop with ecchymoses, which heal within one to two weeks. Usually, healing occurs periodically without scarring. Systemic symptoms include abdominal pain, nausea, vomiting, diarrhea, weight loss, headache, blurred vision, paresthesia, as well as menstrual abnormalities.

Psychiatric comorbidities: Dissociative disorders, anxiety and depression.

2.9. Olfactory Reference Syndrome

This disorder is characterized by persistent preoccupation with the belief that one is emitting a perceived foul or offensive body odor or breath, unnoticeable or only slightly noticeable to others. Olfactory Reference Disorder has been recognized as a distinct category in ICD 11. The affected individual repeatedly checks for smell, often tries to camouflage the smell in perfumes and often asks for reassurance from others. Treatment approach is the same as other OCRDs: high dose SSRIS or clomipramine along with CBT, although trials specific to this disorder are lacking.

3. Secondary psychocutaneous Disorder

Chronic skin diseases, affecting exposed body areas, commonly lead to embarrassment, poor self-image, anxiety, depression, and even suicidal ideation. This is more common in the younger age group. Social impact is also huge. Often, they may have to face social isolation and discrimination and, at times, have difficulty getting jobs. Approximately 50% of acne patients report emotional stress in close association with exacerbation of acne lesions. An Indian study found psychiatric morbidity in 35% of acne patients.[21] Studies have revealed a prevalence of depression in around 30% cases of alopecia areata. Another Indian study found psychiatric morbidity in 52% of patients with chronic dermatoses.

Generally, dermatologists refer these patients to psychiatrists when they find it difficult to keep them well, without improvement of their psychiatric conditions.

Treatment of dermatological disorders, side-by-side management of psychiatric disorders to be done for optimum cure of these patients.

Identification of stress, anxiety, adjustment issues and management with proper counselling, psychotherapy including CT, BT, CBT is helpful.

Antidepressants like SSRI/SNRI/doxepin or hydroxyzine (if severe pruritus) are effective and a short course of BZD may be helpful during bouts of severe anxiety.

Lifestyle modification and stress management are also essential

4. Cutaneous Sensory Disorders

Patients complain of abnormal skin sensations (itching, burning, pain) without the presence of primary skin lesions and a negative medical work up. These sensations can occur in any body region but tends to develop in areas with greater density of epidermal innervation, most commonly involving face, scalp, or perineum.[22]

Glossodynia

Patients with glossodynia presented with chronic pain or burning sensations affecting the tip and sides of the tongue. There may also be changes in smell and taste. Glossodynia usually affects women in their 50s and is observed in over 5% of patients seen by dentists. The condition is usually idiopathic, but may result from vitamin B deficiencies, diabetes mellitus, candida infections, hormonal changes around menopause, and problems related to dentures or dental fillings. Higher rates of anxiety and depression are reported in patients with glossodynia.[22]

Vulvodynia

Vulvodynia is characterized by abnormal sensations in the vulvar region in the absence of skin lesions. The prevalence of vulvodynia is 15 percent in gynecological outpatient practices. Most women with this disorder are between 20 and 50 years of age. They also have altered pain sensation in other parts of the body. There is growing consensus that vulvodynia is a chronic pain disorder. Vulvodynia patients experience more sexual dysfunction because of this discomfort. Amitriptyline, SSRIs, venlafaxine, gabapentin and pregabalin have been found to be effective treatments. CBT and biofeedback have also been found to be effective.

5. Dermatological side effects of Psychiatric Drugs

Cutaneous lesions and various dermatological side effects of psychotropic medications are summarized in Table 2. Severe Cutaneous Adverse Reactions (SCARs) are potentially lethal events (10%–30% mortality) that occur rarely (2%–3% of hospitalized patients) but in a sudden and unexpected manner. Various types of SCARs are Acute Generalized Exanthematous Pustulosis (AGEP), Stevens–Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reactions with Eosinophilia and Systemic Symptoms (DRESS).[23] The basic identifying characteristics along with common psychotropics that may cause these reactions are summarized in Table 3. Psychiatrists should educate their patients and attendants regarding the possibilities of severe cutaneous reactions so that they are informed immediately and can take necessary measures including referral or hospitalization.

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