K Pavithrana, Pabin Pavithranb
a. Department of Dermato-Venereology, Medical College, Calicut; b. Co-operative Hospital, Vadakara

ABSTRACT

Background: Psoriasis, a papulosquamous disorder, continues to be one of the common diseases affecting the skin. Estimates of its occurrence in different parts of the world vary from 0.1 to 3 %.

Objective: To describe the diagnostic features of different types of Psoriasis and their medical management.

Result: Various clinical types of psoriasis include psoriasis vulgaris, gultate, pustular, plaque, exfoliative, flexural and arthritic psoriasis and psoriasis unguis are described here.

Psoriasis, a  papulosquamous disorder, continues to be one of the common diseases affecting the skin. Estimates of its occurrence in different parts of the world vary from 0.1 to 3 %.  Onset of psoriasis is most common in the second to fourth decades of life. Its  high  familial occurrence suggests that genetic factors  play a role in its etiology.   Focal  benign epidermal hyperplasia  results   in  well-defined erythematous scaly  plaques.   The scales are dry, loose  and  micaceous.  Various clinical types  of psoriasis include psoriasis vulgaris, gultate, pustular, plaque, exfoliative, flexural and arthritic psoriasis and psoriasis unguis.

Psoriatic Arthritis

Psoriatic arthritis is an  inflammatory arthritis associated with psoriasis usually with a negative test for rheumatoid factor. Arthritis occurs in about 5% to 10% of patients with psoriasis.  Onset of arthritis is concurrent with the skin disease in 10% of cases but rarely may precede it. Like cutaneous psoriasis, psoriatic arthritis also is a genetically determined disorder.   HLA studies reveal that  the B27,  DR3, A26 and B38 haplotypes are significantly associated with psoriatic arthritis.  Environmental factors like trauma may precipitate arthritis. It occurs com manly between the ages  of 30  and 55.   There are  five clinical patterns of psoriatic arthritis. They are:

Classic psoriatic arthritis

This form of arthritis involves the distal interphalangeal joints of the fingers and toes. In the acute stage the involved joint is swollen and tender; the swelling  often  includes  juxta -articular  tissues leading to the so-called ‘sausage’ appearance of the affected fingers and toes.  The nails of the affected fingers are usually involved.  If there are more than 30° pits on the fingernail  of a patient with chronic inflammatory arthritis, the diagnosis  of  psoriatic arthritis is confirmed.  About 16% of patients with psoriatic arthritis have the classic form of a1thropathy.

Rheumatoid type of psoriatic arthritis

This is a symmetric polyarthritis similar to rheumatoid arthritis.  It accounts for about 15% of all forms of psoriatic arthritis.   Unlike  the classic type,  the proximal interphalangeal joints of the fingers and toes are affected. They are swollen and tender, and result in a ‘swan neck’ deformity as in rheumatoid arthritis. Serum tests for rheumatoid factor  are usually negative. The anthropathy is less extensive and more benign in its course. Early morning stiffness, fusiform swelling of the proximal interphalangeal joints of the fingers,  symmetrical involvement and  the  late deformity of ulnar deviation all pathognomonic of rheumatoid
arthritis are usually not seen in psoriatic arthritis.

Arthritis mutilans

This type accounts for about 5% of all forms of psoriatic arthritis.   Osteolysis  and destruction of bones, especially of the hands and feet, result in telescoping of the soft tissue and gross deformities.

Oligoarticular arthritis

This is the most common  type (70%)  of psoriatic arthritis.  Usually a single joint or sometimes a few interphalangeal or metacarpophalangeal joints  are affected. This form is characteristically asymmetrical in distribution.

Psoriatic spondylitis

An association between  psoriasis  and ankylosing spondylitis  was noted at a much later date than its association  with  peripheral arthritis.   Though radiological evidence of spondylitis is seen in 30% of patients with psoriasis, clinical disease occurs in few. The concept of  psoriatic spondylitis  has  been strengthened  by epidemiologic studies showing an increased incidence of ankylosing spondylitis and sacroiliitis in patients with psoriasis.

Arthritis is a common  accompaniment  of pustular psoriasis.   A recent report  describes the  autopsy findings in 2 cases of generalized pustular psoriasis with    associated  aseptic  purulent arthritis. Histopathological study of the synovium revealed invasion by polymorphonuclear leukocytes, edema and dilatation of small vessels. Levels of immunoreactive leukotrienes B4 and C4  were significantly increased in the synovial fluid; the former attracted PMNLS to the joint and the latter caused exudation of synovial fluid.

Helliwell et al recently classified  psoriatic arthritis into three subgroups; peripheral  arthritis, spondyloarthropathy and  extraarticular  osseous disease. This last subgroup also contains SAPHO syndrome and POPP syndrome.

SAPHO  syndrome  was first described  Benhamon et  al in  1988.   The  acronym  SAPHO  stands  for synovitis, acne,  pustulosis, hyperostosis  and osteomyelitis. Most cases were initially repot1ed from Japan.   Osteoarticular  involvement  occurs on  the anterior  chest  wall   in  the   form   of  sternocostoclavicular osteoarthritis and hyperostosis.  The cutaneous manifestations include  palmoplantar pustulosts and acne.   Rarely, psoriatic skin lesions and sacroiliitis may also occur.

Unless the radiologist is aware of this syndrome, it may be mistaken for tumour or infection.  The skin lesions need not always accompany the osteoarticular manifestations, but may develop later. There is some evidence that Propionibacterium acnes infection may be involved in its pathogenesis, at least in some cases.

The  POPP syndrome,  the acronym  for  ‘psoriatic onychopachydermo-periosteitis’ is another subset of psoriatic arthritis. There is painful onychopathy, soft tissue swelling above  the tenninal  phalanues  and radiological signs of periosteal reaction with bone erosions.  The big toes are predominantly affected. The distal interphalangeal joints remain unaffected. Onycholysis and longitudinal ridging are the nail changes always seen. Acral solid periosteal reaction and bone condensation leading to the ‘ivory’ phalanx are radiologic features.

Many  other conditions have  been  reported  in association with psoriatic arthropathy. They include ocular lesions like conjunctivitis, iritis, scleritis and keratoconjunctivitis sicca, ulcerative colitis, Reiter’s disease, Behcet’s  syndrome,   myopathy, aortic incompetence, amyloidosis and Crohn’s disease.

Radiologic features of Psoriatic Arthritis

The radiologic features of psoriatic arthritis closely simulate those of rheumatoid arthritis. The changes are  asymmetric oligoarticular in psoriasis.   The peripheral joints as well as the spine may be involved. Important  changes in  the  peripheral joints  are osteolysts  wh1ch results  in whittling  away of  the phalanges, metacarpals and metatarsals. Destruction of the terminal phalangeal tufts may occur (acro-osteolysis)  and in the most severe form, the bones completely disappear.  Along with destruction   new bone formation also occurs. Due to this the phalanges show  splaying  of  their  bases  causing   ‘fish-tail’ deformity or  more  commonly  ‘pencil-in-cup’ deformity.

Erosions may also occur in the bones and in the early stages cannot  be  easily  differentiated  from ‘osteolysis’.  Early  erosions occur  subarticularly. Later considerable cystic destruction of the affected bones occurs,  but the articular cartilage  is often spared in the destructive process, as indicated by the lack of narrowing of the joint space. Bony ankylosis of the Joints may occur. Osteoporosis  occurs less often in psoriatic arthritis.  Psoriatic arthritis  has a predilection for the distal interphalangeal and proximal interphalangeal joints with relative sparing of the metacarpophalangeal and metatarsophalangeal joints.

Asymmetric sacroiliitis may occur in about 20% of psoriatics.   Erosions,  narrowing and  fusion   of sacroiliac joints may  occur.    Often atypical syndesmophytes  may be present without sacroiliitis. The cervical spine shows radiographic changes more frequently than the rest of the spine. Various patterns of vertebral and paravertebral ossification may be seen.  Marginal and non-marginal syndesmophytes occur.  The non-marginal type appears as ‘inverted comma’ . ‘tear  drop’ or as  ‘bag – pipe’  forms. Paravertebral ossification (By-waters-Dixon lesion) may rarely be seen.

Treatment

Psoriatic arthritis has a chronic course with periods of remission  and  exacerbation.   The  course and prognosis in a particular patient is unpredictable. Various drugs  may give symptomatic  relief  to the patient and may prolong remission.

Retinoids

Etretinate and its active metabolite acitretin used in the treatment of   psoriasis.      They have immunomodulatory action in treatment of psoriasis.1 Since acitrelin is eliminated rapidly from body long term contraception in women patients is not required. Though there are conflicting reports on the efficacy of retinoids in the treatment of psoriatic arthritis,2,3 the authors of one study considered etretinate to be the one of the first choices in the treatment of psoriatic arthritis. They administered it in a daily dose of 1 mg/ kg for 1 month, followed by maintenance dose of 25 mg/day  or, where possible  10 mg per day or on alternate days for a maximum period of 25 months. Common side effects associated  with oral retinoids are cheilitis, dryness of nasal mucosa and epistasix, alopecia, conjunctivitis, nausea, vomiting. diarrhoea and raised  level s of SGPT  and  hyper  lipidemia. Rarely raised intracranial tension, papilloedema and toxic liver necrosis may occur.

Methotrexate

Methotrexate  is the commonly  used  systemic  drug in the treatment of  psoriasis.   Psoriatic arthritis especially its mutilating variety not controlled  with NSAID responds well to methotrexate. It is given in a dose of 7.5mg weekly. Before initiation of tl1erapy. the full blood count and renal and hepatic function tests  should   be  done.    Adequate  contraceptive measures  may be commenced  where appropriate. To reduce incidence of nause 5mg of folic acid can be given daily.   Hepatotoxicity is a major concern with a 7% overall risk of severe fibrosis/cirrhosis in psoriatics.  The  risk  factors are  total  dose  of methotrexate above 2.5 g, past history of hepatitis B or C infection, diabetes and obesity.  Baseline liver biopsies as well as pretreatment hepatitis B and C serology have been recommended, but the usefulness of a baseline biopsy in the absence of risk factors has been questioned.    The  risk  of fibrosis  due  to methotrexate  should  be balanced  with the risk of biopsy related complications.  In one study bleeding complicated 1.7% of liver biopsies and there were 0.13 – 0.33% liver biopsy related deaths.4

Considering high  morbidity  associated  with  liver biopsy, there is a need for non invasive techniques to screen for liver fibrosis and cirrhosis.  Serum assays for products of matrix synthesis or degradation and the enzymes involved in the  process  have been investigated as markers of liver fibrosis.  The aminotenninal propeptide of type III collagen (P III NP) is the serum marker investigated in patients receiving methotrexate.5

P III NP is cleaved during collegen synthesis, which is upregulated in active fibrogenesis. Proton magnetic resonance spectroscopy (HMRS) is able to measure liver fat content non invasively.  A combination  of HMRS and PMRS (which estimates cell membrane turn over and fibrosis) is the most suitable techniques for monitoring methotrexate-induced liver toxity.6

Biologics

Biologics are the new introduction in the treatment of  psoriatic  arthritis. There  are 4 basic  potential strategies  for immunomodulation with  biological therapy in psoriasis. They are:

  1. Targeting pathogenic T -cell
  2. Inhibition of T-cell activation
  3. Induction of immune deviation
  4. Inhibition of cytokines.

Once an appropriate target strategy is chosen, biological can be produced  by recombinant DNA technique.

Biologic therapies for psoriasis on or close to market are: Alefacept, Etanercept, Infliximab,  Efalizumab and Adalimumab.

Etanercept:

Composed of 2 soluble TNF receptor (P 75) domains fused to human immunoglobulin, etanercept neutralizes the inflammatory cytokines TNF and lymphotoxin alpha. Administered subcutaneously 25 mg twice weekly, it has shown excellent safety and efficacy in the treatment of psoriatic arthritis. Study it as shown  that at 12 weeks,  87 % of patients achieved a clinical response by the Psoriatic A1thritis Response Criteria compared with 23 % of the placebo  group. The drug is generally well tolerated and well-suited to long-term therapy in psoriatic arthritis.

Infliximab:

1t is a chimeric  monoclonal antibody that has high specificity, affinity and avidity for TNF-µ.  This is also effective i n the treatment of psoriatic arthritis.

Non steroidal anti-inflammatory agents

The commonly  used NSAIDS eg: indomethacine, phenylbutazone, salicylates and ibuprofen cannot be safely administered for treatment of psoriatic arthritis because they  may rarely  exacerbate psoriasis. Chloroquine, a drug commonly used in rheumatoid arthritis is also  known  to exacerbate psoriasis. Meclofenamate another  NSAID is an appropriate drug for psoriatic arthritis.

Corticosteroids

Corticosteroids both systemic and intra articular give excellent therapeutic  response, but  often  causes recurrence of the disease in a more severe form on cessation  of   therapy.  Still they   are   often recommended for severe mutilating arthropathy.

End Note

Author Information

  1. Dr. K Pavithran, MD, D.V.D, MNAMS,
    Emeritus Professor, Dermato-Venereology, Medical College, Calicut, Senior Consultant, MIMS Hospital, Calicut 16.
    E-mail: dr_pavithran-md@yahoo.com.
  2. Dr. Pabin Pavithran, M.B.B.S., D.D.V.L. Skin Specialists, Co-operative Hospital, Vadakara

Conflict of Interest: None declared

References

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  2. Johnson TM, Rapini RP. Isotretinoin-induced thrombocytopenia. J Am Acad Dermatol. 1987 Nov;17(5 Pt 1):838–9. [Pubmed]
  3. GUBNER R. EFfect of “aminopterin” on epithelial tissues. AMA Arch Derm Syphilol. 1951 Dec 1;64(6):688–99. [Crossref]
  4. Perkins W, Williams RE, Vestey JP, Tidman MJ, Layton AM, Cunliffe WJ, et al. A multicentre 12-week open study of a lipid-soluble folate antagonist, piritrexim in severe psoriasis. Br J Dermatol. 1993 Nov;129(5):584–9. [Pubmed]
  5. Zachariae H, Kragballe K, Søgaard H. Methotrexate induced liver cirrhosis. Studies including serial liver biopsies during continued treatment. Br J Dermatol. 1980 Apr;102(4):407–12. [Pubmed]
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