69 year-old man with 5 days of fever and flu like symptoms with associated abrupt onset of markedly edematous and erythematous plaques on the anterior chest, upper and lower extremities

Figure 1 Eye lesion showing conjunctival injection

Figure 2 Pustular lesion on the hand

Figure 3 Lesions on the anterior chest wall

Figure 4 showing lesions on the upper extremities

Figure 5 showing lesions on the lower extremities

Laboratory Data

Lab results showed pancytopenia and elevated ESR. Throughout his hospital course, his labs were notable for significant elevation of CRP, ESR, and fibrinogen levels with pancytopenia and mild elevation of ALT, AST and total bilirubin and decreasing iron, eGFR and albumin levels.

Serology for ANA was postive

Serology was negative for viral studies (Influenza A and B, Parvo 19, Hepatitis A,B, C)

Negative for PPD, lyme, syphilis and ehrlichia studies.

Positive for recent or past EBV infection.

A bone marrow biopsy was performed and the result revealed myelodysplatic syndrome with high index of suspicion for AML.

A punch biopsy was performed at the advancing border of an active lesion on the right side of the chest and the left lower leg.

H&E staining revealed diffuse dermal neutrophilic infiltrates with karyorrhexis and a preserved and normal epidermal layer. The diagnosis on the pathology report was leukocytoclastic vasculitis for both lesions.

We feel this diagnosis is debatable and open for discussion as noted in this document.

Figure 6

Figure 7

Figure 8

Figure 9

Sweet's Syndrome (Acute febrile neutrophilic dermatoses)

Does this case support the diagnosis for Sweet’s Syndrome?

How do we distinguish neutrophilic dermal infiltrates of Sweet’s syndrome from typical leukocytoclastic vasculitis?

Sweet’s Syndrome was first described in 1964 by Dr Robert Douglas Sweet. The syndrome is characterized by acute febrile neutrophilic dermatosis. There are two major and four minor criteria for diagnosis of the syndrome; however two major and two minor criteria are needed for the establishment of the diagnosis (1).

It is interesting to note that there was no specific confirmed diagnoses established during the patient’s hospital course in spite of multiple diagnostic. The patient’s initial presentation as well as an abrupt onset of skin lesions and the bone marrow biopsy result strongly suggested that was a hematopoietic malignancy-associated Sweet’s syndrome.

The patient exhibited two minor criteria including the accompanying associated malignancy, myeolodysplastic syndrome with a high index for suspicion of AML, including the presence of fever and constitutional signs and symptoms. He had the one major criteria of abrupt onset of typical cutaneous lesions. The other major criterion is histopathology consistent with Sweet’s syndrome which is dense diffuse dermal infiltrate composed primarily of neutrophils with absence of leukocytoclastic vasculitis. The patient’s skin punch biopsy revealed neutrophilic dermal infiltrate with preservation of the normal epidermis which was reported as leukocytoclastic vasculitis (LCV). However the patient’s histopathologic features did not demonstrate obvious erythrocyte extravasation, leukocyte infiltration of vessel walls or fibrinoid necrosis of the vasculature which are necessary to diagnose LCV (3).

Another unusual finding in this patient was systemic leukocytopenia rather than leukocytosis, which is one of the four minor criteria. However, in patients with malignancy-associated Sweet’s syndrome, neutropenia has been observed. (2)

According to Cohen, Talpaz and Kurzrock in their review of the world literature in 1988, there have been reported 79 cases of malignancy-associated Sweet’s syndrome. More than 85% of individuals with malignancy-associated Sweet’s syndrome had a hematologic disorder, most commonly AML. Solid tumors were observed in approximately 15% of malignancy-associated Sweet’s syndrome patients; nearly two-thirds of these individuals had carcinomas of the genitourinary organs. A hematologic malignancy and a solid tumor were concurrently present in two patients with malignancy-associated Sweet’s syndrome (3).

Our patient had a history of prostate cancer with radical prostatectomy 5 years prior to an admission that led to chronic urinary incontinence. Although Sweet’s syndrome usually resolves itself, hematopoietic malignancy related Sweet’s syndrome could be deadly with a suppressed immune system. Our patient gradually failed and died 2 days after his 70th birthday due to respiratory failure by contracting herpes simplex. It was his wish to allow this case to be reported in the hope that he might contribute towards a better understanding of Sweet’s syndrome.

1. Bolognia J. Jorizzo J, Rapini R. Dermatology. 2 nd edition. Spain: Mosby; 2008.
2. Liu CI, et al. Sweet syndrome with histiocytoid infiltrate and neutropenia: A rare combination. J Am Acad Dermatol. 2009; 61: 5
3. Cohen PR, et al. Malignancy-associated Sweet’s syndrome: Review of the world literature. J Clin Oncol. 1988;6: 1887-1897
4. Jayachandran NV, Thomas J, Chandrasekhara PK, Kanchinadham S, Kadel JK, Narsimulu G. Cutaneous vasculitis as a presenting manifestation of acute myeloid leukemia. Int J Rheum Dis. 2009 Apr;12(1):70-3.
   
   One of the rare causes of secondary vasculitides is malignancy. Hematological malignancies produce secondary vasculitis more frequently than solid malignancies. Here in we report a case of acute myeloid leukemia presenting with anti-neutrophil cytoplasmic antibody-positive vasculitis. This case highlights the importance of looking for underlying malignancies, especially leukemias in patients presenting with features of systemic vasculitides
   
5. Morand JJ, Lightburn E, Richard MA, Hesse-Bonerandi S, Carsuzaa F, Grob JJ. [Skin manifestations associated with myelodysplastic syndromes] Rev Med Interne. 2001 Sep;22(9):845-53. [Article in French]
   

   PURPOSE: Our purpose was to describe cutaneous manifestations associated with myelodysplastic syndromes. METHODS: Data from seven patients with cutaneous vasculitis (four cases), neutrophilic dermatosis (one case), relapsing polychondritis (one case), and possible erythema elevatum diutinum (one case) in association with myelodysplastic syndrome (refractory anaemia RA, RA with excess of blasts--RAEB-, RAEB in transformation RAEBt, chronic myelomonocytic leukaemia--CMML-), and analysis of the literature were reviewed. RESULTS: The cutaneous manifestations of myelodysplastic syndrome may or may not be specific, and may reveal hemopathy transformation. The cutaneous vasculitis are the most frequent and polymorphic. The relation with neutrophilic dermatosis is more specific; they are a spectrum of diseases including pyoderma gangrenosum, Sweet's syndrome, erythema elevatum diutinum (nuclear segmentation anomalies of neutrophils both in the skin and in the blood are a biological marker of the association). Relapsing polychondritis is significantly associated with myelodysplastic syndromes. Their pathogenesis are controversial. CONCLUSION: Early biopsy of cutaneous lesions in myelodysplastic syndromes is indicated. Analysis of blood cell count (and more bone marrow biopsy in relapsing polychondritis) is indispensable in these neutrophilic cutaneous or vasculitis diseases

sweet's syndrome, leucocytoclastic vasculitis, myelodysplastic syndrome

Bhushan Kumar MD, Professor, Former Head, Department of Dermatology, PGIMER, Chandigarh, India on May 17, 2010

It is difficult to believe that all lesions spread all over the body could be attributed to Sweet's Syndrome. Many lesions could be due to extravasations due to pancytopenia or non specific hypersensitivity phenomenon due to AML. Some of lesions may be due to intensive drug therapy.

Classical vasculitis in Sweet's Syndrome does not occur or is uncommon. Obviously this is not a straight forward case of Sweet's Syndrome.

Khalid Al Aboud MD, Medical Director and Consultant Dermatologist, King Faisal Hospital, Makkah, Saudi Arabia on May 18, 2010

Interesting case. Similar to Dr Kumar, I have the feeling that it is not Sweet's Syndrome. Simply, it might be a vasculitis.

David Elpern MD, Dermatologist, Williamstown, MA, USA on May 18, 2010

This is an extraordinarily complex case and Ms. Cohen is to be congratulated for presenting it. I think the key thing here is to nail down the hematologic diagnosis which was likely the trigger for the skin lesions. Both leucocytoclastic vasculitis and Sweet's Disease have been associated with myelodysplastic syndrome and AML. So, a comment from a hematologist is in order. Also, it would be of interest for her skin slides to be seen by one of our dermatopathologists. Neutrophilic dermatoses of many types are associated with hematologic malignancies. Ms. Cohen, you've come so far on this - there is still more to learn. This case will stick with you for the rest of your career, and what you learn from this unfortunate patient will help others in the future.

Osler wrote: "Given the sacred hunger and proper preliminary training, the student-practitioner requires at least three things with which to stimulate and maintain his education, a note-book, a library and a quinquennial brain dusting. I wish I had time to speak of the value of note-taking. You can do nothing as a student in practice without it. Carry a small note-book which will fit into your waistcoat pocket, and never ask a new patient a question without note-book and pencil in hand......Begin early to make a three-fold category - clear cases, doubtful cases and mistakes." This is still somewhat of a doubtful case. Any effort you expend at this point will be a great learning opportunity. After you synthesize our comments and perhaps others, please submit a followup note so we all can learn from you.

Abdullah Mancy MD, Al-Ramadi Teaching Hospital, Ramadi, Iraq on May 18, 2010

Usually bullous or necrotic lesions occur in the syndrome caused by underlying malignancy which could be solid or haematopoeitic malignancy. What about oral cavity? Its involvement is more common in malignancy.

But presence of focal leucocytoclastic vasculitis does not exclude the diagnosis of Sweet syndrome.

Robert I.Rudolph, M.D., FACP. Clinical Professor of Dermatology, University of Pennsylvania, Philadelphia, PA, USA on May 19, 2010

This does not look at all like Sweet's to me. It looks like a vasculitis or drug reaction. Both of the latter, of course, have been well reported to occur with underlying malignancy.

J. Andrew Carlson, MD, FRCPC, Professor, Divisions of Dermatopathology and Dermatology, Department of Pathology, Albany Medical College, Albany, NY, USA on May 19, 2010

I would get levels to exclude an adjacent focus of suppurative folliculitis. It's a neutrophilic dominant process and it appears to be a nodular infiltrate with nuclear debris both around vessels (in the center of the infiltrate) and interstitially. The adjacent dermal vessels do not appear to be involved/show findings of vasculitis as would expect if it was LCV.

If you asked me to pick one diagnosis over the other - late, resolving lesion of neutrophilic vasculitis. Other diagnoses to keep in mind pustular drug eruption.

Ronny Zarro MD, Arbil, Iraq on May 20, 2010

If one consider the revised diagnostic criteria of Sweet's syndrome the patient had both major criteria and 3 (although 2 are required) minor criteria which is quite enough to make the diagnosis of Sweet's syndrome. Conjunctivitis occur in 30% of patients with Sweet's syndrome

Adel Aly MD, Dermatologist, Egypt on May 21, 2010

Yes this supports the diagnosis. Vasculitis can occur as a secondary event due to release of proteases from neutrophilic infiltrate but as you mentioned no extravasation or fibrinoid necrosis. One thing is why you neglect the possibility of pulmonary involvement as a result of Sweet's since it can lead to bronchiolitis oblitrans and even respiratory failure. Regarding the clinical appearance do not forget that pustular vasculitis of hands is considered by some as one variant of Sweet's

Khalifa Sharquie MD, PhD. Professor and Chairman of Iraqi Board of Dermatology, Iraq on May 21, 2010

I am not happy at all with diagnosis of Sweets. I am more in favour of suppurative folliculitis where all the features of the disease could be explained like fever, joint pain etc and this could be seen in myeloproliferative disorders.