Psoriasis with special reference to Unani medicine – A review

: Background. Psoriasis is a chronic and recurrent inflammatory skin disorder that affects about 125 million people worldwide. Patients with psoriasis are more likely to develop inflammatory arthritis, cardiometabolic disease, and mental health issues. Psoriasis remains incurable and recurrent despite the availability of contemporary treatments. Unani (Greco-Arabic) medicine has its unique concept of psoriasis; numerous treatments and formulations are prescribed by renowned Unani scholars. Objective. This study sought to provide an understanding of psoriasis in conventional medicine, as well as clinically equivalent conditions documented by ancient Unani academics in their writings, such as Rūfas, Jālinūs, Rāzī, Ibn Sīna, Majūsi, Ibn-i Zuhr, Ibn al-Quf, and Ibn-i Hubal Baghdādi. Methods. The Unani classical literature was researched manually and online for this purpose. PubMed, Science Direct, and Google Scholar were utilized to assemble all the classic and contemporary psoriasis disease-related literature. Results. Since antiquity, Unani scholars have advocated


Introduction
Skin disorders are one of the most common human conditions, affecting people of all ages and 30%-70% of the population [1].Psoriasis is derived from the Greek word psora, which means "itch," or psorin, which means "to itch."[2][3][4][5].The reported prevalence of psoriasis in countries ranges from 0.09% to 11.4%; the prevalence among adults in India ranges from 0.44% to 2.8% [6].According to some research, males are twice as likely to be affected as females, and the majority of patients are in their third or fourth decade of life.Psoriasis can occur at any age; however, it is uncommon in children younger than five years [7].It is defined as an autoimmune, inflammatory condition characterized by red, inflamed plaques, and macules caused by excessive proliferation and poor differentiation of keratin-producing epidermal cells.Frequently, these plaques are accompanied with silvery scales.[7].It is a persistent, noncommunicable, irritating, disfiguring, and debilitating disease that has a significant negative impact on the quality of life of those suffering from it [8].The exact cause of psoriasis is still being researched, and the mechanism of immune response is also not well understood.However, hyperproliferation of keratinocytes, acanthosis, parakeratosis, and T cells' mediated inflammatory response can be the basic pathophysiology [9,10].Despite the abundance of therapeutic choices, a complete cure with minimal or no side effects remains elusive [11].The primary therapy options consist of topical steroids, PUVA, and biologics, all of which have distinct limitations [12].Therefore, quest for an alternative treatment option for psoriasis is the need of the hour.
Unani medicine envisions the human body comprises seven main components: Arkān (elements), Mizāj (temperament), Akhlāṭ (humours), A'ḍā' (organ), Rūḥ (pneuma), Quwā (faculties), and Af'āl (functions) i.e., called as Umūr-i Tabi'iyya.The mere absence or derangement of any component threatens the very existence of health and causes disease [16].The Unani system of medicine is founded on both scientific and holistic conceptions of health and healing.Its fundamental principles, diagnoses, and treatment modalities are all based on these beliefs: its holistic approach takes into account the whole person rather than a reductionist approach toward health and disease [14].The demand for Unani Medicine is increasing continuously as a result of its efficacy and minimal adverse effects [15,17,18].The present review provides the comprehensive details of psoriasis and its management strategies currently available in modern science as well as those described in classical Unani texts [19].

Methodology
The authors methodically examined ancient and contemporary literature in search of psoriasis references to compile and contextualize the facts and data relevant to the historical background, etiology, pathophysiology, clinical features, diagnostics, and treatment of psoriasis.In the classical Unani literature, the description using the words Taqashshur al-Jild, Qashaf Jild, Chambal, Da al-Sadaf, Samakiah, Sadafia, Apras, Sa'fa Qishr, Talaq, and Quba Mutaqashshira was thoroughly analyzed.These phrases were also entered into electronic databases such as PubMed, ScienceDirect, DOAJ (The Directory of Open Access Journals), Google Scholar, and the Ayush Research Portal.The Boolean operators 'AND' or 'OR' were utilized effectively for the specific facts pertaining to etiology, pathophysiology, clinical characteristics, diagnostics, and treatment in both conventional and Unani medicine.Unani terms and transliterations were derived from the most recent terminology standard for Unani.
Rūfas , a renowned Unani physician, described a skin condition known as "Talaq" in which white scaly lesions resembling bark appear on the affected area.Galen of Pergamon (131-201 CE), physician of a Roman emperor, used the term psoriasis to describe itchy, scaly lesions of the eyelids and scrotum [2,31].Pliny, a Roman encyclopedia author, noted "psora" in his book "Naturalis Historia" and advised that cucumber root could be used to treat it [32].
In the later eighteenth century, Robert Willan (1757-1812CE), a British physician, authored the book "on cutaneous illness" and devised an improved, user-friendly taxonomy of skin illnesses based on eight recurring lesions.He coined the term 'psoriasis' to designate the papulosquamous disorder in the group squamae, along with lepra, pityriasis, and ichthyosis, and distinguished it from leprosy (psora leprosa and lepra Greco rum).He described various types of psoriasis, including guttata, diffusa, gyrata, palmaria, unguium, and inveterata.In Willan's view, the disease begins on the knees and elbows and then advances to the scalp, fingernails, and toenails [46].
Jean Louis Alibert (1768-1837CE), a French physician who worked and taught at the St. Louis Hospital in Paris, which was devoted to skin problems, disagreed with Wil-lan's classification and sought to organize and systematize skin disorders.He developed an "Arbre des dermatoses" in 1829 CE, dividing skin illnesses into 12 separate groups.Psoriasis, along with leprosy, was categorized as dartrous dermatosis.The 19th century CE has seen the establishment of hospitals and clinics dedicated only to the treatment of skin or venereal illnesses, giving physicians ample chance to evaluate more cases of skin diseases such as psoriasis [21,31].
Heinrich Koebner (1838-1904CE) observed the isomorphic effect of irritation (Koebner phenomenon; 1872CE): the development of a psoriatic lesion at the site of mechanical or other injury.This phenomenon was subsequently utilized in trials to investigate the earliest changes caused by psoriasis [2,31,47].Moreover, Heinrich Auspitz (1835-1886 CE) observed the incidence of papillary hemorrhage following the removal of psoriatic lesion scales (Auspitz sign or bloody dew phenomenon).D. Turner, R. Willan, and F. Hebra had previously recognized this sign [2].At the end of the nineteenth century, Hebra, Unna, and William Munro characterized psoriatic micro morphology by defining the micro-abscess (micro-pustule), i.e., the concentration of neutrophils in the stratum corneum of the skin.[49].During the early years of the 20th century, Woronoff's description of a pale halo encircling a psoriasis plaque became known as the "Woronoff ring" after the Auspitz sign and Koebner phenomenon.Then, these three phenomena/signs became established indicators that made psoriasis patients easy to diagnose for clinicians.[50].In the second part of the 20th century, it was determined that the psoriatic epidermis has 25 times more mitosis per unit than the epidermis of healthy people.Van Scott and Ekel demonstrated that the cell cycle of keratinocytes in psoriatic patients is greatly reduced, from around 311 hours in normal individuals to 36 hours in psoriatic patients; furthermore, the turnover period of the epidermis is likewise significantly decreased, from 27 days to 4 days [32].In 1973, Moll and Wright demonstrated that psoriasis-related arthritis is distinct from rheumatoid arthritis (Figure 2) [51].Numerous immunological studies conducted over the past few decades have revealed that psoriatic patients have altered innate and adaptive immune systems, allowing for a better knowledge of the pathogenesis of psoriasis and the development of novel therapeutic methods [52].

Epidemiology
The occurrence of psoriasis varies by country, ranging from 0.09% to 11.43% [53].Globally, psoriasis affects, on average, 2% to 5%, of the population [54].Despite its global distribution, its prevalence varies by geography and ethnicity.In general, as latitude increases, prevalence increases [55].As a result, psoriasis is less prevalent in Asian and African countries than in tropical regions such as Europe and Australia.Men and women are equally susceptible to psoriasis, but the disease impacts women far earlier.Recent research indicates that the disease's prevalence has increased exponentially in recent years.[56].

Psychosomatic paradigms in psoriasis
The National Psoriasis Foundation of the United States reports that psoriasis has a substantial impact on mental and emotional health, in addition to its effects on physical health [57].Patients with psoriasis endure feelings of self-consciousness, agitation, and helplessness.Other patients try to disregard the great discomfort and severity of the disease, as well as its negative psychological impacts, which can result in a vicious cycle of despondency for many psoriasis sufferers.The social stigma associated with the illness contributes to depression and poor psychosocial functioning [58]: psoriasis patients have increased suicidal ideation compared to the general population, and the prevalence ranges from 4% to 21.2% in different nations [59].The condition has the greatest psychological and social impact on women, adolescents, and minority groups [60].Psoriasis has also been associated with stress-related diseases and behavioral disorders [61].According to recent research, the fraction of patients identified as "stress reactors" appears to have a better longterm prognosis, as well as the early deployment of psychological therapies that may alter the course of the disorder [60].

Chronic plaque psoriasis / nummular psoriasis / psoriasis vulgaris
The plaque or nummular kind of psoriasis is the most prevalent, affecting about 80 -90% of sufferers [64].It is characterized by erythemato-squamous plaques.The lesion is round or oval, ranges in size from the size of a coin to a huge palm, and affects the elbows, knees, scalp, lumbosacral region, retro auricular region, inter-gluteal cleft, and umbilical region (Figure 3) [65,66].

Guttate psoriasis
This is a typical type of psoriasis that develops rapidly and is more prevalent among adolescents and young adults.The size of the lesion ranges from a pinhead to a pea (0.5-1.5 cm in diameter).These raindrop-like lesions, which resemble erythematous papules, erupt quickly and are distributed bilaterally symmetrically throughout the entire body, largely on the trunk and upper extremities while avoiding the palms and soles.Other risk factors include intensive local therapy or removal of systemic glucocorticoids.Streptococcal pharyngitis may occur 1 to 2 weeks prior to the onset or exacerbation of the condition.Throat swabs are required to rule out streptococcal infection, and an increased Anti-streptolysin-O (ASO) titre is typically observed in this condition [62,67].

Erythrodermic Psoriasis
This type of psoriasis is characterized by extensive erythema and scaling on the face, hands, feet, nails, trunk, and limbs.It may develop in patients with a history of chronic disease, as a side effect of poorly tolerated topical medication, such as chloroquine or adrenergic receptor blockers, or as a result of intense light therapy, such as ultraviolet B or UVB.This disorder exhibits all psoriasis symptoms, but erythema is the most prominent.Additionally, systemic symptoms such as hyper-or hypothermia, dehydration, hypoproteinemia, electrolyte imbalance, anemia, hypocalcemia, renal and heart failure are noted [68][69][70].

Psoriasis inversus (Flexural Psoriasis)
An inverse form of psoriasis affects about 2%-4% of patients.It impacts the axilla, groins, sub-mammary folds, vulva, gluteal cleft, periumbilical region, retro-auricular region, and glans of the uncircumcised penis [66].It is more prevalent among adults than among children.The lesions are well-defined, less scaly and smooth, with a glazed look and a small number of deep, painful fissures [3].

i.
Generalised pustular psoriasis) (Von Zumbush): Generalized pustular psoriasis, the most severe form of pustular psoriasis, affects children aged 1 to 5 years.The lesions begin abruptly as many erythematous, painful plaques, which rapidly convert into small, sterile pustules the size of pinheads.There are pustules on the trunk and extremities.Erythema and pustules are preceded by fever, leucocytosis, musculoskeletal discomfort, malaise, and a burning feeling [72].Nail alterations are prevalent when there is a subungual pus accumulation.Involvement of the tongue and buccal mucosa is also possible.Systemic steroids worsen pustular psoriasis [73,74].i.

Localised pustular psoriasis (Barber's Psoriasis):
It is also known as palmoplantar pustulosis because the lesions often affect the palms and soles.It is more likely to affect females.The lesions are erythematous, well-defined, and covered with a large number of tiny pustules on the thenar and hypothenar prominences of the palms, soles, and sides of the heels.The skin is scaly, red, and prone to fissures; certain pus-tules may be hemorrhagic.Patients may develop concomitant arthropathy, especially of the distal interphalangeal joints [68,75].

Psoriasis arthropathica/arthritis psoriatica
Psoriatic arthritis is an autoimmune inflammatory illness characterized by psoriasis and arthritis, in addition to the absence of rheumatoid factor in the blood.It affects 5%-10% of psoriasis patients, reaches its peak between the ages of 20 and 40, and is uncommon in children.Both genders are equally affected.It might develop either before or after the skin symptoms.HLA B27, DR3, A26, and B38 haplotypes are genetically substantially related with psoriatic arthritis [72,76].

• Scalp Psoriasis:
The scalp is commonly affected.The scaling areas are interspersed with normal skin, and their lumpiness is felt rather than seen, but considerable hair loss is rare.Psoriasis frequently extends beyond the edge of the scalp [77].

• Napkin Psoriasis:
A psoriasis form outside the napkin (nappy/diaper) area may be the first sign of a psoriatic propensity in an infant.It often resolves rapidly, although there is an increased chance of acquiring psoriasis in later years [78].

Etiology
The specific etiology of psoriasis is still being investigated; however, psoriasis is considered to be a complex inflammatory illness with recognized risk factors such as genetic factors, environmental variables, emotional stress, skin infection, mechanical stress (Koebner's phenomenon), drugs, alcohol, smoking, etc. [9,10].The heredity of psoriasis is between 60% and 90%, which is higher than most other multifactorial disorders [80].The majority of psoriasis-associated genes are involved in the immune response, whereas only a minority encode for skin-specific proteins.
Psoriasis patients have a higher prevalence of HLA-Cw6 compared with healthy controls.Moreover, the etiology of psoriasis is connected with TNF-alpha, another protein-coding gene associated with innate and adaptive immune response.In addition, genes associated with Th17-cell activation have been shown to play a pathogenic role in psoriasis patients [80][81][82].Psoriasis is considered to be initiated by external stimuli, including trauma, infection, and drugs in genetically sensitive individuals.
The host DNA forms complexes with antimicrobial peptides released from keratinocytes (skin cells) in response to a stimulus, resulting in inflammation and keratinocyte proliferation that manifests as illness [82,83].Numerous factors, including adolescent and pregnancy-related physiological changes, frequent infections, hormonal imbalances, physical harm (particularly exposure to sunlight), and psychological stress, contribute initiating the condition.Psoriasis has also been linked to the use of antimalarial, β-blockers, anti-malignant, immunosuppressive, nonsteroidal anti-inflammatory drug (NSAID), and lithium drugs.Moreover, it may be exacerbated by obesity, drunkenness, smoking, and dryness of the skin [84].
On the other hand, Unani physicians have compiled the following list of causal elements based on traditional Unani concepts.In addition, various Asbāb-i Bādiya (external) and Asbāb-i Sābiqa (internal factors), which are responsible for the disease and may function in combination or alone, have been described.

Pathophysiology
Psoriasis is a hyperproliferative disorder with a complex sequence of inflammatory mediators.The mitotic activity of basal and suprabasal cells is significantly increased, and after a few days, basal cells migrate to the stratum corneum.The silver scales on psoriasiform lesions are nothing more than a layer of dead cells (Figure 4) [82,87].Early clinical investigations using TNF inhibitors revealed the significance of these cytokines in psoriasis, prompting the disorder to be viewed as being predominantly driven by T-helper-1 (Th-1) cells [88].However, data suggests that T-helper cells releasing interleukin (IL)-17 and IL-23 play a critical role in the development of psoriasis [89,90].These cytokines are currently believed to play a fundamental role in the pathogenesis of psoriasis, as evidenced by the success of therapies that inhibit IL-17 or IL-23 pathways [83,88,89].
Regarding the pathophysiology of Taqashshur al-Jild, the Unani scholar Ibn-i Zuhr indicated that an excessive amount of abnormal Sawdā (black bile) accumulates in the skin, interfering with skin nutrition and preventing the skin from expelling abnormal Sawdā (black bile).As a result, skin tissues die and shed as scales [39].According to Majusi, Tabī'at (medicatrix naturae) expels diseased humor from internal organs to the skin, causing dryness and itchiness.If the threshold is exceeded, the skin becomes incapable of removing Khilt-i Ghalīz (morbid humor) [35].

Morphology of psoriatic lesions:
In psoriasis, the primary lesion is a mild itchy papule or plaque that is well-circumscribed, indurated, erythematous, scaly, or plaque-like [6].

Site of predilection:
According to the Koebner or isomorphic phenomena, it affects pressure sites such as the elbows, knees, scalp (from which it can spread to the forehead and nape of the neck), extensor surface, lumbosacral area, and back [6].
According to ancient Unani academics, the clinical characteristics of Taqashshur al-Jild are roughness, itching, scaling, and skin peeling.Razi defined Taqashshur al-Jild as having roughness, itchiness, and spherical scales on the body [45].There are pustules on various surface locations and burst-like peeling of the skin.Talliya is a condition in which the nails become micaceous white and as brittle as lead [45].According to Ahmad bin Mohammad Tabari, this is a skin ailment characterized by the development of scales on the affected areas [22].These characteristics of the disease, as described in classical Unani literature, closely resemble those of psoriasis.

Signs
Candle grease sign: When a psoriatic lesion is scuffed with a glass slide, candle-grease-like scales appear, often known as the "Signe de la taches de bougie" [91].

Grattage test:
The lesion is lightly scraped with a glass slide to produce the silvery scales [62].

Membrane of Bulkeley:
When all scales are removed, the basement membrane is exposed, revealing a moist, red surface known as the Bulkeley membrane [91]  Auspitz sign: Capillaries on the tops of elongated papillae are broken during a thorough scrape, resulting in multiple bleeding sites known as the Auspitz sign [67,76,93] Holo or Woronoff sign: Following treatment with ultraviolet radiation or topical steroids, the absence of prostaglandins leads to the formation of a zone of hypopigmentation surrounding the plaques known as Holo or Woronoff sign [75,94] Koebner's or isomorphic phenomenon: It is characterized by the formation of isomorphic lesions at the site of an unrelated skin injury.Typically, lesions form seven to fourteen days following an injury.For Koebner's phenomenon to occur, both the epidermis and dermis must be injured [70,76].

Nail changes in psoriasis
• Pitting of nail plate: This condition is characterized by depressions in the nail surface and typically affects the fingernails.Due to improper development of the superficial layers of the nail plate, nail pitting can occur [67,70,95].• Oil drop sign: On the nail bed of the digit, a circular yellow discoloration with a well-defined brown rim like an oil droplet is seen [67,69].

Diagnostics
A family history of psoriasis, the presence of lesions at specific areas, such as the elbow, knee, scalp, back, and nails, lesions coated with silvery scales, the candle grease sign, the Auspitz sign, and the Koebner phenomenon, irritation, and seasonal variations are used to diagnose psoriasis.Investigations include the ESR, which is usually normal but can be high in generalized pustular psoriasis, the TLC, which is high in psoriasis, the serum calcium, which is low in pustular and erythrodermic psoriasis [67], serum uric acid, which is elevated in up to 89% of patients [69], immunoglobulins, which are generally normal, but IgA deficiency and monoclonal gammopathy are documented in association with psoriasis.Moreover, anti-nuclear antibodies, which are found in rheumatoid arthritis but negative in psoriatic arthritis [69]; throat swab, which is useful in guttate psoriasis [91]; nail dipping and skin scraping, which are carried out to exclude the fungal infection because it is negative in psoriasis [96]; and skin biopsy, which is performed to confirm the diagnosis by histopathological examination of psoriasis are included in the diagnostics [62,66].

Combination therapy:
In more severe forms of psoriasis, a combination of treatment modalities may be employed to enhance the benefit and to lower toxicity.Such combinations include acitretin +UVB light , acitretin +PUVA [99,102], methotrexate + UVB light [98], PUVA+UVB light [103], and Methotrexate + Cyclosporine [99,103].

'Ilāj (Treatment)
Complete cure and effective treatment are perpetual challenges for clinicians.In the Unani system of medicine, the pathogenesis is based on humoral theory, and several humours are involved in the development of psoriatic lesions; melancholic humour predominates and may be produced from bilious humour, phlegmatic sanguineous humour, or melancholic humour itself.Thus, there is a typical presentation that resembles the characteristics already mentioned for such melancholic conditions in traditional Unani literature.Taqashshur al-Jild is one of the clinical conditions characterized by prominent melancholy [110].Using the same postulated guidelines, the treatment can also be administered.In this sense, Unani medicine corrects the normal physiology of cells, tissues, organs, and systems by expelling the pathological aberrant humour.Therefore, the medications are also useful in reducing the severity of the symptoms, reducing presentations, and relapse [13].To attain the aforementioned goals, the condition may be treated using one of the following three modalities: 'Ilāj bi'l-Tadbīr (Regimenal Therapy), 'Ilāj bi'l Ghidhā' (Diet Therapy), and 'Ilāj bi'l Dawā (Drug Therapy).

Ilāj bi'l-Tadbīr (Regimenal Therapy): This type of
Unani therapy facilitates the waste disease material resulting from the derangement of Khilṭ (humour) to be expelled from the body using a variety of procedures such as Fasd (venesection), Hijama (cupping), Ta'līque (leeching), and Ta'rīque (sweating).).These plant medicines may be useful in the treatment of Sawdāwī diseases like psoriasis [6].

Clinical trials
Recent clinical investigations have evaluated the efficacy and safety of numerous traditional Unani medicines.Table 1 provides the essential details of the reported clinical trials.

Case reports
A number of case report studies on various Unani formulations with clinically and statistically meaningful outcomes were also accessible.Thus,

Discussion
The Unani system of medicine has a long and glorious background of promoting health, preventive measures, and management of diseases through its holistic approach based on time-tested drugs and therapies.Psoriasis is a chronic inflammatory skin disease characterized by erythematous, circumscribed scaly papules and plaques; it can cause itching, irritation, burning, and stinging [128].
Psoriasis patients have a higher risk of inflammatory arthritis, cardiometabolic illness, and mental health problems.Although there is no formal description of psoriasis in the Unani system of medicine, Taqashshur al-Jild presents similarly to psoriasis.There are significant parallels between Taqashshur al-Jild and psoriasis; nonetheless, these diseases have diverse pathology [111].According to Unani concept Taqashshur al-Jild (psoriasis) is defined as a type of skin disease characterized by roughening and hardening of affected part of the skin accompanied by sloughing of fish-like scales and itching [114].Tabi'at expels Khilt-i Ghalīz from internal organs to the skin, causing dry skin and itchiness.If it builds up further than the limit, the skin seems unable to remove Khilt-i Ghalīz leading to accumulation of Khilt-i Sawdā in skin and produces Taqashur al-Jild [35].The Unani system of medicine has been treating psoriasis with numerous therapeutic methods since ancient times with 'Ilāj bi'l Ghidhā' (diet therapy), 'Ilāj bi'l-Tadbīr (regimenal therapy), 'Ilāj bi'l Dawā (drug therapy) [114].Numerous clinical investigations on various Unani single and compound formulations have demonstrated its efficacy in the treatment of psoriasis Table 1.Nonetheless, the studies had significant shortcomings, including inappropriate use of scales, improper or no use of a control drug, absence of drug identification and chemical fingerprinting.Few research have analysed the effect in terms of clinically relevant differences; the majority of studies have merely reported statistical significance.In a handful of studies, recurrence assessment was also performed.
Therefore, additional research with well-planned randomized control trials and validated outcome measures is necessary to uncover the influence of these medications in the treatment of psoriasis and substantiate the claims made by ancient physicians.In addition, a major issue with published studies is the lack of standardization in the reporting of clinical trial results, which should be addressed in future publications.

Conclusion
This article attempted to summarize the details of psoriasis in both Unani and conventional medicine.This analysis also highlights the treatment method and possibilities accessible in Unani medicine that must be validated by scientific measures.In addition, the status of clinical trials on psoriasis in Unani medicine was discussed so that future studies might be planned with the incorporation of conventional medicine and validated outcome measures, and published according to standard reporting requirements.

Figure 3 .
Figure 3. Abdominal skin of patient with plaque psoriasis

Table 1 .
Summary of clinical trials conducted on several Unani medications