Neutrophilic dermatoses Flashcards
Epi of sweets syndrome?
The average age of onset is 30-60, female predominance of 4 to 1
What is the treatment effect that suggests that something is Sweet’s syndrome?
Rapid response to steroids
What are the two major criteria for Sweet’s syndrome?
- Abrupt onset of typical cutaneous lesions
- Histopathology consistent with Sweet syndrome
What are the 5 major clinical and histological subtypes of Sweet’s syndrome?
Classic (60-70%), cancer-associated (10-20%), Inflammatory disease-related (10-15%), drug-induced (5%), and pregnancy (2%)
What is the clinical presentation of Sweet’s syndrome?
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%
What is the clinical progression of Sweet’s syndrome?
Resolves in 5-12 weeks, recurs in 30%
When do lesions usually occur in drug-induced Sweet’s as compared to drug administration?
Usually 1-2 weeks after drug administration
Aside from the skin, what other sx’s can be seen in sweet’s syndrome?
Fever (50-80%), malaise, preceding URI or flu-like sx’s, leukocytosis (70%), arthralgias/arthritis, ocular involvement (conjunctivitis, episcleritis, iridocyclitis)
What are some infectious triggers of Sweet’s?
Viral: URI, CMV, HBV, HCV, HIV
Bacteria: Strep, Yersinia
Mycobacteria: atypical mycobacteria, BCG vaccination, M. tuberculosis, M. Leprae
Fungi: dimorphic, including sporotrichosis and coccidiomycosis
What autoimmune disorders are associated with sweet syndrome?
SLE, RA, DM, relapsing polychondritis, Sjögren syndrome, autoimmune thyroid dz, sarcoidosis, behçet disease
What malignancies can be associated with Sweet’s?
Hematologic (10-20% of cases), in particular, AML
- Myelodysplasia
- Solid-organ, predominantly the more common primary carcinomas
What is the histology of Sweet’s syndrome?
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
What uncommon systemic findings can be seen in Sweet’s Syndrome?
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
What is hystiocytoid sweets more strongly associated with and what stain should be done?
Dermal and or SQ infiltrate of neutrophils and “histiocytoid” cells, stain for MPO –> strong a/w malignancy
What is subcutaneous sweets?
Neutrophils involve subcutis in a lobular pattern; p/w deep-seated red nodules on extremities
What is neutrophilic dermatoses of dorsal hands?
This is tender, erythematous to violaceous plaques that may become bullous or ulcerative. May represent a subtype of Sweet’s
What is the treatment for Sweet’s?
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.
What are some alternative steroid-sparing drugs that can be used in Sweet’s?
Potassium iodide (900mg/day), dapsone (100-200mg/day), and colchicine
What is the pathogenesis of pyoderma gangrenosum?
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
What types of pyoderma gangrenosum are most strongly a/w malignancy?
Bullous (less destructive than ulcerative form)
What is the clinical progression of classic (ulcerative) pyoderma gangrenosum?
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
What diseases is vegetative pyoderma gangrenosum associated with?
None
What is the histology of pyoderma gangrenosum?
- 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
What are some treatments for pyoderma gangrenosum?
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
What is the pathophysiology of behçets?
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.
What are the diagnostic criterion for Behçets disease?
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
What areas do the genital ulcers of Behçets disease usually involve?
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.
What are some systemic complications that can occur in Behçet’s disease?
- 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
What is the histology of Behçet’s disease?
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
What is the epidemiology of Bowel-associated dermatosis arthritis syndrome?
Usually seen 1-6 yrs after patients have…
- undergone intestinal bypass surgery
- have blind loops of bowel following surgery
- had biliopancreatic diversion
- gastrointestinal disorders
Pathophysiology of bowel-associated dermatosis-arthritis syndrome?
- 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
What is are the clinical features of bowel-associated dermatosis arthritis syndrome?
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
Treatment for bowel-associated dermatosis arthritis syndrome?
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
What is SAPHO?
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
Clinical manifestations of SAPHO?
Essential elements: osteoarticular lesions, pustular dermatoses ( ~30% of children and ~85% of adults.)
- Affected bones = tender, swollen joints = painful
- Febrile, leukocytosis, elevated ESR
Diagnosis of SAPHO?
Bone scintigraphy: increased uptake
MRI : assessing joint and tissue involvement, can be used for monitoring
Osteoarticular involvement is intermittent with periodic exacerbations and remissions
Treatment for SAPHO?
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.
