CLINICAL HISTORY:

Signs and symptoms:  Patient complained initially of pruritis with subsequent burning pain of skin, which worsened with movement. Patient had concomitant fever up to 103.7, nausea, anorexia, and malaise. .

Previous Treatment:  Psoriasis in the past had been controlled with topical mid to high potency steroids as well as dovonex oint.

Other information:  The patient was seen approximately 6 days prior to admission by her dermatologist for a worsening of her psoriasis. She was noted to have multiple erythematous macules confluent to patches in the flexor areas and concomitant silvery plaques on the extensor surfaces of her elbows and knees. At that time the patient was started on triamcinolone 0.1% cream BID and dovonex ointment BID to the affected areas. Over the course of 6 days her rash became wide spread over her entire body with formation of pustules and was admitted to the hospital by her pediatrician.

PHYSICAL EXAM:

temp 103.1, Heart rate 104, Respiratory rate 18, Blood pressure 108/62
Gen: Awake, Alert, Oriented X 4, ill appearing female with guarding of movement secondary to pain.

Skin: Diffusely erythrodermic with multiple pustules confluent to lakes of pus on trunk, face, and extremities. Multiple areas of denuding skin were noted. A mild fecal odor was noted.

HEENT: Neck was supple, oral phary7nx was noted to have slight erythema and mild fissuring of the lips.

Remainder of exam was unremarkable.

LABORATORY TESTS:

Labs: abnormalities on Day 1 wbc 18.4, Hb 11.2, Hct 33.4 on Day 7 wbc 10.9 Hb 11.8 Hct 34.2 remainder of blood work including liver functions were normal.

DERMATOHISTOPATHOLOGY:

Skin biopsy revealed parakeratosis, prominent Munro’s microabcesses, focal spongiform pustule formation, and superficial and deep polymorphous infiltrate, containing multiple polymorphonuclear leukocytes, psoriasiform acanthosis and papillary dermal telangectasia and edema.

DIFFERENTIAL DIAGNOSIS:

1.   Pustular Psoriasis
2.   Steven’s Johnson’s Syndrome
3.   TEN
4.   Kawasaki’s Disease
5.   Acne Fulminant

SCROLL DOWN FOR ANSWER AND DISCUSSION.

CORRECT DIAGNOSIS:

Generalized Pustular Psoriasis (Von Zumbusch Psoriasis)

DISCUSSION:

Psoriasis is a papulosquamous skin disease. While the primary pathologic process is unknown, it is likely to be a disregulation of activated T-cell interacting with antigen presenting cells and over production of pro-inflammatory cytokines with tumor necrosis factor alpha being prominent among these. This pro-inflammatory process of the dermis causes inflammation of the dermis and hyper proliferation of the epidermis with abnormal differentiation.

Psoriasis is seen in 1-2% of the population. Heredity seems to play a role in psoriasis with increased susceptibility to psoriasis in HLA class I and II major histocompatability complex on human chromosome 6(17q)1. A variety of HLA associations have been reported whereas HLA-B27 is associated with pustular psoriasis, HLA-B 13 and B 17 are increased with guttate and erythrodermic psoriasis ~.
Psoriasis may be exacerbated by infection, stress, pregnancy, withdrawal of systemic steroids, and drugs such as beta-blockers, calcium channel blockers, ACE inhibitors, lithium, iodine’s, indomethacine, interferon, antimalarials, minocycline, glyburide, terbinafine, and gemfibrozil.

Psoriasis of the skin presents in a variety of types: Plaque, guttate, erythrodermic, localized pustular, and generalized pustular psoriasis (Von Zumbusch psoriasis). Generalized pustular psoriasis usually develops in a patient with preexisting history of psoriasis, usually plaque type but may also occur denovo. It can appear quickly within as little as a few hours with the skin becoming red covered with red macules and patches which may be painful. They progress to tiny pustules and then coalesce into pustules at the borders. There is a predilection for flexor areas and skin fold areas i.e. breast, groin, and axilla but it may occur everywhere and may encompass most of the body in severe cases. This may occur in cycles of days to weeks. The pustules may have a fetid odor and they may dry to form yellow-brown crusts over a red surface. Pruritis and pain are common. Mucous membrane lesions are also common, along with geographic tongue. Patients are usually quite ill and may have fever, chills, tachycardia, anemia, cachexia, and weakness. Lab abnormalities include leukocytosis, hypocalcaemia, and hypo albumenemia. Systemic and life threatening complications include pneumonia, acute renal failure, congestive heart failure, acute respiratory distress syndrome, hepatitis, and sepsis secondary to the exfoliate dermatitis.

TREATMENT:

Treatment must be immediate, since this can be life threatening, comprehensive, and aggressive. Goals toward preventing fluid loss and risk of infection should be addressed first, next is the treatment of psoriasis and treatment of systemic complications. Hospitalization with bed rest, mild sedation, and analgesic therapy along with 1V fluid are given for supportive care. Wound debridement and whirlpool baths may be necessary for cases with more extensive skin surface area involvement. If infection is present, broad-spectrum antibiotic therapy with particular attention to staph and strep species should be prescribed. Wet dressing and mid potency steroid help in mild outbreaks2. Systemic therapy should be started for moderate to severe disease.

For years standard systemic therapies for acute generalized pustular psoriasis have consisted of PO/IM methotrexate, retinoids (acitretin) and cyclosporin. These medications are efficacious but do have considerable side effect profiles. Methotrexate should have co administration of folate or leucovorin and even with this, life-threatening myelosuppression can occur, and long term usage requires dose dependant liver biopsy and increased risk of cirrhosis of the liver. Acitretin therapy is associated with elevated triglycerides and lowering HDL cholesterol with elevations of AST and ALT. In addition, great caution must be used in women of childbearing age 2o to the high risk of teratogenicity of acitretin potentially for 3-5 years after discontinuing medication. Long term effects also include skeletal and ligamentous calcifications and hyperastosis4. Cyclosporin, although effective, is associated with hypertension and concerns of renal failure these medications when stopped have been associated with rebound of pustular psoriasis.

Because of the significant side effects of these medications and the recent implication of tumor necrosis factor alpha (TNFa)5, the recent productions of drugs, which are monoclonal antibodies to TNFa, new therapeutic options are now available. These agents i.e. inflixamab and etanercept seem to offer similar efficacy with a potentially marked decrease in side effects for acute treatment of pustular psoriasis. Case reports of infliximab for the treatment of pustular psoriasis by Ebewski et al 6and Kierdul F. et at7 and etanercept by Kamarashev, J et. al.8 have shown marked improvement with this new class of drugs. Since these medications have not been studied in a randomized blinded scientific trial, this authors recommendation for acute generalized pustular psoriasis would be to start an established medication i.e. methotrexate of acitretin and simultaneously start etanercept or infliximab and when the patient has received adequate therapeutic benefit to wean them slowly off the 1st agent but continue the TNFa agent for long term therapy, thereby minimizing the side effect profile of the aforementioned drugs, and decreasing the risk of rebound pustular psoriasis.

REFERENCES:

1. Andrews Diseases of the Skin Clinical Dermatology, Ninth Edition .Odom, RB; James, WD; Berger, TG. Pg 223

2. Habif A Color Guide to Diagnosis and Therapy - Clinical Dermatology, Third Edition. Habif, T. pg 192

3. Treatment of generalized pustular psoriasis: a multicenter study in Japan. Ozawa, A;
Ohkido, M; Haruki, Y; Kobayashi, H; Ohkawara, A; Ohno, Y; Inaba, Y; Ogawa, H.
Journal of Dermatology. 26(3):141-9, 1999Mar.

4. Oral retinoids--efficacy and toxicity in psoriasis. Gollnick, HP. British Journal of Dermatology. 135 Suppl 49:6-17,1996 Oct

5. Lack of association of TNF-238A and 308A in Japanese patients with psoriasis vulgaris, psoriatic arthritis and generalized pustular psoriasis. Nishibu,A: Oyama, N:
Nakamura, K; Kaneko, F. Journal of Dermatological Science. 29(3):181-184, 2002 Sep

6. Lnfliximab for the treatment of severe pustular psoriasis. Elewski, BE et al. Journal of the American Academy of Dermatology 2002Nv;47(5):796-797

7. Rapid response to infliximab in severe pustular psoriasis, von Zumbusch type.
Newland, MR; Weinstein, A; Kerdel,F. International Journal of Dermatology. 41(7):449-
52,2002Jul.

8. Generalized pustular psoriasis induced by cyclosporin withdrawal responding to tumor necrosis factor alpha inhibitor evanescent. Kamarashev J; Lor P; Forester a; Heinzerling L; Burg g; Dermatology 2002;205(2): 213-216

Additional Comment:

© Copyright 2003-2006 by AOCD Grand Rounds

Top of Page