Neutrophilic dermatoses

Question 1

Epi of sweets syndrome?

Answer 1

The average age of onset is 30-60, female predominance of 4 to 1

Question 2

What is the treatment effect that suggests that something is Sweet’s syndrome?

Answer 2

Rapid response to steroids

Question 3

What are the two major criteria for Sweet’s syndrome?

Answer 3

1. Abrupt onset of typical cutaneous lesions
2. Histopathology consistent with Sweet syndrome

Question 4

What are the 5 major clinical and histological subtypes of Sweet’s syndrome?

Answer 4

Classic (60-70%), cancer-associated (10-20%), Inflammatory disease-related (10-15%), drug-induced (5%), and pregnancy (2%)

Question 5

What is the clinical presentation of Sweet’s syndrome?

Answer 5

Upper RTI or flu-like illness frequently precedes the development of the syndrome

Fever occurs in 40–80% of patients

Tender, non-pruritic, erythematous plaques or papules, which may enlarge or coalesce to form plaques

favors the head, neck and upper extremities (including the dorsal aspect of the hands)

malignancy-associated cases =more widespread distribution

EN like lesions (neutrophilic panniculitis) = subcutaneous sweets

+pathergy (Like PG)

Resolves in 5-12 weeks, recurs in 30%

Question 6

What is the clinical progression of Sweet’s syndrome?

Answer 6

Resolves in 5-12 weeks, recurs in 30%

Question 7

When do lesions usually occur in drug-induced Sweet’s as compared to drug administration?

Answer 7

Usually 1-2 weeks after drug administration

Question 8

Aside from the skin, what other sx’s can be seen in sweet’s syndrome?

Answer 8

Fever (50-80%), malaise, preceding URI or flu-like sx’s, leukocytosis (70%), arthralgias/arthritis, ocular involvement (conjunctivitis, episcleritis, iridocyclitis)

Question 9

What are some infectious triggers of Sweet’s?

Answer 9

Viral: URI, CMV, HBV, HCV, HIV

Bacteria: Strep, Yersinia

Mycobacteria: atypical mycobacteria, BCG vaccination, M. tuberculosis, M. Leprae

Fungi: dimorphic, including sporotrichosis and coccidiomycosis

Question 10

What autoimmune disorders are associated with sweet syndrome?

Answer 10

SLE, RA, DM, relapsing polychondritis, Sjögren syndrome, autoimmune thyroid dz, sarcoidosis, behçet disease

Question 11

What malignancies can be associated with Sweet’s?

Answer 11

Hematologic (10-20% of cases), in particular, AML

• Myelodysplasia
• Solid-organ, predominantly the more common primary carcinomas

Question 12

What is the histology of Sweet’s syndrome?

Answer 12

Dense, diffuse infiltration of superficial to deep dermis and sometimes underlying panniculus, by neutrophils

Lymphocytes, histiocytes, and eosinophils also present

Leukocytoclastic debris

Papillary dermal edema, sometimes marked

Vasculopathy with perivascular neutrophilic inflammation that extends to traverse endothelial linings common; however, true vasculitis with fibrinoid necrosis is absent

Question 13

What uncommon systemic findings can be seen in Sweet’s Syndrome?

Answer 13

Neutrophilic alveolitis (CXR findings of interstitial infiltrates, nodules, pleural effusions), multifocal steril osteomyelitis, renal involvement, myositis, hepatitis, pnacreatitis, ileitis, colitis, aseptic meningitis, encephalitis, hearing loss

Question 14

What is hystiocytoid sweets more strongly associated with and what stain should be done?

Answer 14

Dermal and or SQ infiltrate of neutrophils and “histiocytoid” cells, stain for MPO –> strong a/w malignancy

Question 15

What is subcutaneous sweets?

Answer 15

Neutrophils involve subcutis in a lobular pattern; p/w deep-seated red nodules on extremities

Question 16

What is neutrophilic dermatoses of dorsal hands?

Answer 16

This is tender, erythematous to violaceous plaques that may become bullous or ulcerative. May represent a subtype of Sweet’s

Question 17

What is the treatment for Sweet’s?

Answer 17

Sweet syndrome is a “benign” condition which, if left untreated, may persist for weeks or months.

Cutaneous lesions then involute spontaneously, rarely leaving scars

recurrences develop in ~30% of patients (with or without treatment)

more often in those with hematologic disorders (~50%)

Therapy: oral prednisone (0.5–1.0 mg/kg/day) for 2–6 weeks.

There is prompt relief of not only the cutaneous, but also the extracutaneous, manifestations.

In some patients, prolonged low-dose prednisone for an additional 2–3 months may be necessary to suppress recurrences.

If lesions = few and localized topical superpotent or intralesional corticosteroids may prove helpful.

Question 18

What are some alternative steroid-sparing drugs that can be used in Sweet’s?

Answer 18

Potassium iodide (900mg/day), dapsone (100-200mg/day), and colchicine

Question 19

What is the pathogenesis of pyoderma gangrenosum?

Answer 19

The disease is idiopathic in 25–50% of patients,

However, an underlying immunologic abnormality likely, given its frequent association with AI systemic diseases

Enhanced activity of the IL-1 pathway is thought to play a role in PG, as it does in several autoinflammatory disorder

Question 20

What types of pyoderma gangrenosum are most strongly a/w malignancy?

Answer 20

Bullous (less destructive than ulcerative form)

Question 21

What is the clinical progression of classic (ulcerative) pyoderma gangrenosum?

Answer 21

Lesions usually begin as a tender papulopustule with surrounding erythematous/ violaceous induration, an erythematous nodule, or a bulla

the papulopustule may be follicular

All lesions undergo necrosis leading to a central shallow or deep ulcer

loss of tissue can expose underlying tendons or muscles.

When fully developed, ulcer has a purulent base with an irregular, undermined and overhanging, gunmetal-colored border which extends centrifugally

Re-epithelialization occurs from the margins and the ulcers heal with atrophic cribriform pigmented scar

Question 22

What diseases is vegetative pyoderma gangrenosum associated with?

Answer 22

None

Question 23

What is the histology of pyoderma gangrenosum?

Answer 23

• Earliest lesions present as intraepidermal or subepidermal neutrophilic abscesses
• Variable epidermal necrosis
• Ulcers characteristically undermine
• Diffuse, dense neutrophilic infiltrate within the dermis in later lesions
• True vasculitis is lacking

Question 24

What are some treatments for pyoderma gangrenosum?

Answer 24

Good wound care

Search for underlying dz

For mild dz can consider intralesional steroids or systemic steroids for more severe dz (.5-1mg/kg/day)

For recalcitrant dz can try infliximab and cyclosporine

Question 25

What is the pathophysiology of behçets?

Answer 25

Genetic and environmental factors \>80% of Asian patients have the HLA-B51 allele, but it is present in only about 15% of Caucasians from Western countries. -HSV, hepatitis C virus, parvovirus B19, and streptococci infections may potentially trigger an immunoregulatory defect in a genetically predisposed individual. The pathomechanisms of Behçet disease involve vascular injuries and autoimmune responses. immune complexes, neutrophils appear to be responsible -\>mucocutaneous lesions neutrophils produce an increased amount of superoxides and lysosomal enzymes -\> enhanced chemotaxis lead to tissue injury elevated circulating levels of TNF-α, IL-1β and IL-8 result in activation of neutrophils and augmentation of interactions between neuts and endothelial cells Clonal expansion of autoreactive T cells that recognize a peptide derived from heat shock protein 60 has also been described. Recent genome-wide association studies found that single nucleotide polymorphisms in IL-10 and IL-23R regions were associated with the disease.

Question 26

What are the diagnostic criterion for Behçets disease?

Answer 26

Recurrent oral ulceration (aphthous oral ulceration recurring at least 3x in a 12-month period + 2 of the following: - Recurrent genital ulceration (aphthous genital ulceration or scarring observed by physician or pt - Eye lesions: anterior or posterior uveitis; cells in the vitreous by slit lamp exam; or retinal vasculitis observed by an ophthalmologist - Cutaneous lesions: ERythema nodosum-like lesions observed by physician or patient; papulopustular lesions or pseudofolliculitis; or characteristic acneiform nodules observed by a physician in a post-adolescent patient not on corticosteroids Pathergy test

Question 27

What areas do the genital ulcers of Behçets disease usually involve?

Answer 27

Genital aphthae involve primarily the scrotum and penis in men and the vulva in women Compared to oral lesions, the anogenital aphthae tend to be larger with irregular margins, but can vary in size (Fig. 26.15C) more painful Distinction of genital lesions from lesions of HSV requires viral culture,DFAstain, or PCR.

Question 28

What are some systemic complications that can occur in Behçet's disease?

Answer 28

- Ocular (leading cause of morbidity): happens in 90% of patients, can be painful and lead to blindness. Findings include uveitis (poster uveitis most characteristic), but can also lead to conjunctivitis, glaucoma, cataracts, vasculitis - Joints: 50% of pts w/ arthritis. Mono and polyarthritic, non-erosive. Most common on the knees, wrists, ankles - GI: It can be difficult to distinguish from IBD. Ulcerations can occur in the esophagus, small bowel and colon - Neurologic: Usually appears later and is associated w/ poor prognosis. can have CN palsies, brainstem lesions, acute menigo-encephalitis - Vascular: aneurysmal or occlusive arterial dz. increased risk of superficial and deep venous thrombosis - Cardiopulmonary: coronary arteritis, valvular dz, myocarditis. Recurrent ventricular arrhythmias, pulmonary arter aneurysms - Renal: can cause glomerulonephritis

Question 29

What is the histology of Behçet's disease?

Answer 29

Ulcers generally are nonspecific but may show vasculitis Neutrophilic dermal infiltrate in pustular lesions and those secondary to pathergy (where leukocytoclastic vasculitis may sometimes be seen) Vasculitis: lymphocytic or leukocytoclastic Thrombophlebitis Vasculopathy: intravascular thrombi with mild vascular inflammation Erythema nodosum–like lesions show acute vasculitis within the subcutaneous fat in addition to septal and/or lobular inflammation

Question 30

What is the epidemiology of Bowel-associated dermatosis arthritis syndrome?

Answer 30

Usually seen 1-6 yrs after patients have... - undergone intestinal bypass surgery - have blind loops of bowel following surgery - had biliopancreatic diversion - gastrointestinal disorders

Question 31

Pathophysiology of bowel-associated dermatosis-arthritis syndrome?

Answer 31

- Usually bacterial overgrowth in a blind loop of bowel --\> immune complexes containing bacterial antigens are then deposited within the skin and synovium - There is a pathogenic role of bacteria in this syndrome, this is supported by the disappearance of the disease with ABX or surgery

Question 32

What is are the clinical features of bowel-associated dermatosis arthritis syndrome?

Answer 32

characterized clinically by constitutional flu-like symptoms, skin lesions and a variety of systemic complications occur from 1 to 6 years after the responsible bowel surgery. Constitutional symptoms: usually present, precede --Cutaneous eruption, similar to those of serum sickness --\> e.g. fever, chills, malaise, arthralgias and myalgias. - Erythematous macules --\> progress to papules and purpuric vesiculopustules w/in 48 hours and last 2–4 weeks - These may recur at 4- to 6-week intervals. - Tend to favor proximal extremities/ trunk

Question 33

Treatment for bowel-associated dermatosis arthritis syndrome?

Answer 33

**Curative:** Surgery, revision of the bowel bypass, surgical resection of the blind loop of bowel **Not curative:** - Cutaneous and rheumatologic manifestations: systemic prednisone - Should not use systemic CS as long-term tx - Antibiotics that have proven to be beneficial

Question 34

What is SAPHO?

Answer 34

Synovitis, acne, pustulosis, hyperostosis, and osteitis - Represents a wide spectrum of aseptic neutrophilic dermatoses in a/w aseptic osteoarticular lesions - Have distinctive histologic and radiographic features

Question 35

Clinical manifestations of SAPHO?

Answer 35

**Essential elements:** osteoarticular lesions, pustular dermatoses ( ~30% of children and ~85% of adults.) - Affected bones = tender, swollen joints = painful - Febrile, leukocytosis, elevated ESR

Question 36

Diagnosis of SAPHO?

Answer 36

Bone scintigraphy: increased uptake MRI : assessing joint and tissue involvement, can be used for monitoring Osteoarticular involvement is intermittent with periodic exacerbations and remissions

Question 37

Treatment for SAPHO?

Answer 37

Treatment options: NSAIDs intraarticular CS for arthritis bisphosphonates for bone involvement systemic corticosteroids, other immunosuppressive medications: azathioprine, methotrexate TNF antagonists:etanercept, adalimumab, infliximab IL-1 antagonists: anakinra for both skin and bone disease. Of note, paradoxical induction of SAPHO was observed in a patient with inflammatory bowel disease treated with infliximab.