Hydroxychloroquine

Acute pustular psoriasis is characterized by fiery-red erythema followed by formation of pustules. Precipitating factors include drugs, infections, pregnancy, solar irradiation, and psychological stress. We present a case of a woman who developed acute onset of pustular psoriasis precipitated by hydroxychloroquine therapy and systemic steroids. The patient's course was complicated by leukocytoclastic vasculitis presumptively caused by levofloxacin.

Introduction:

Pustular psoriasis is an acute form of psoriasis characterized by numerous pinpoint pustules appearing in clusters that may coalesce to form lakes of pus. Fever, generalized weakness, malaise, and leukocytosis are prominent features. Numerous triggering factors have been implicated. Drugs (Table I) are most commonly reported as triggering agents although infections (17,18), solar irradiation (15,18,19) emotional stress (19,20), pregnancy (21), and hypocalcemia (22) have also been cited.

Case Report:

A 65 year old female with a past medical history significant for hypertension, chronic renal insufficiency, hyperlipidemia, gout, arthritis, diverticulitis, and recently diagnosed Sjogren's syndrome was referred to the Dermatology Clinic with the complaint of an generalized pustular eruption that began on the upper torso four days prior. The patient was taking losartan, nifedipine, lasix, clonidine, simvastatin, and sulfinpyrazone. She had started hydroxychloroquinine two weeks prior for symptoms suggestive of Sjogren's syndrome. The eruption began on the chest as an erythematous plaque and had been treated with oral corticosteroids.

Physical exam revealed erythematous, arcuate plaques studded with pustules (Figures 1 and 2). Histologically, subcorneal and intercorneal pustules were noted. Bacterial and fungal cultures were negative. The prednisone was tapered, hydroxychloroquine discontinued, and acetretin begun. The patient had an initial white blood cell count (WBC) of 14,000 without signs or symptoms of infection.

[FIGURE 1-2 OMITTED]

In five days, the patient's complete blood count was significant for an increased WBC to 24,200. She was started empirically on levofloxacin 500 mg a day. Three days later, she complained of a new rash on her lower body. The lower extremities had confluent, purpuric plaques with few grayish centers. No pustules remained on the patient's trunk.

Levofloxacin was discontinued. Biopsy of the lesion revealed leukocytoclastic vasculitis. Blood cultures, urine culture and chest roentgenogram were negative. The patient remained afebrile, was treated with topical corticosteroids and anti-pruritics, and required oral narcotics for pain relief. One week after admission, some fading of the initial purpuric lesions was evident. Secondary infection was suspected based on the slow resolving diffuse erythema with yellow crusts. Bacterial cultures of the lesions grew methicillin-resistant staphylococcus aureus. Biopsies demonstrated diffuse impetiginous changes of the epidermis. Aggressive debridement with chlorhexidine brush and soap was performed on a daily basis. Acticoat dressings were applied to pseudoeschar areas. On hospital day 14, she received vancomycin to hasten clearing of the lower extremity lesions. She remained afebrile without leukocytosis or signs of systemic infection. She was discharged after 3 weeks of hospitalization. At follow-up she was markedly improved. Some residual edema and erythema of the lower extremities remained but no recurrence of psoriatic lesions occurred.

Discussion

The average age of onset for pustular psoriasis is 50 years. Males and females are affected about equally (18). Pustular psoriasis may appear as localized pustular psoriasis, which runs a chronic course, or generalized pustular psoriasis (23). The localized form is a chronic pustular dermatosis of the palms and soles and has two main divisions. Acrodermatitis continua usually begins unilaterally as a pustule on the distal extremity often involving the nailbed (Figure 3). Nails may float off in lakes of pus. Massive digital hyperkeratosis may be noted. Eventually, extension to the remaining digits and more generalized flares may occur (Figures 4 and 5). Pustules occur on fiery red skin that is often painful and tender (Figure 6). Chronic palmoplantar pustulosis is a more indolent form of disease. It is often a bilaterally symmetric pustular dermatosis with deep-seated pustules generally restricted to the palms and soles (Figure 7). The generalized pattern (Figures 8-10) is also referred to as the von Zumbusch pattern, named after Ludwig von Zumbusch, who described a pustular eruption in a patient with psoriasis vulgaris in 1910 (24).

[FIGURE 3-10 OMITTED]

Hypocalcemia secondary to concomitant hypoalbuminemia occurs often in patients with yon Zumbusch psoriasis (18,22). Hypocalcemia has also been reported to cause flares of pustular psoriasis that repeatedly cleared in response to restoration of norMal serum calcium levels (22). The pathogenesis of pustular psoriasis is not completely understood.

The differential diagnosis of a patient with a pustular eruption includes pustular psoriasis, acute generalized exanthematous pustulosis (AGEP), and infection. AGEP is usually triggered by a drug in a patient without a prior history of psoriasis. Its course is characterized by rapid spontaneous healing (25). Infectious causes are ruled out by negative gram stain and cultures. In our case, the arcuate nature of the plaques, history of arthritis consistent with psoriatic arthritis, exacerbation by oral corticosteroids, associated toxicity, and slow response to treatment argues in favor of pustular psoriasis.

Therapy is aimed initially at identification and removal of any offending agents. Retinoids such as acitretin at doses of 0.5-1.0 mg/kg/day leads to rapid clearing of pustulation (18,26). Methotrexate (15,18), hydroxyurea (15,18,27), dapsone (18,28), photochemotherapy (10,18), and cyclosporin (29) have also been used with varying degrees of efficacy.

Leukocytoclastic vasculitis (LCV) is a histologic diagnosis characterized by segmental inflammation and fibrin deposition within blood vessels with fragmentation of polymorphonuclear leukocytes and formation of nuclear dust (leukocytoclasis). Infections, chemicals, foods, and drugs can precipitate LCV. LCV may also occur in association with chronic diseases and malignant neoplasms. No cause is identified in 60% of cases (30). The fluoroquinolones ciprofloxacin and ofloxacin have been reported previously as provocative agents of LCV (31,32), but this is the first reported case suggesting levofloxacin-induced LCV.

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MICHAEL JUDE WELSCH MD UNIVERSITY OF CHICAGO, DEPT OF MEDICINE--SECTION OF DERMATOLOGY CHICAGO, IL

ADDRESS FOR CORRESPONDENCE

Michael Jude Welsch, MD

University of Chicago

Dept of Medicine--Section of Dermatology

5841 S. Maryland, MC 5067

Chicago, IL 60637-1470

E-mail: mjudew@hotmail.com

Phone: (773) 702-1611

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