史維德氏症候群(Sweet syndrome)是一種伴隨急性發燒、疼痛像水泡之病灶的疾病。對類固醇的治療反應很好。這一直是皮膚科中相當神秘的一種疾病，直到近幾年來隨著對細胞激素(cytokines)的研究漸多，才比較了解可能的致病機轉以及跟其他發炎性疾病/癌症/藥物的關聯。
Chapter 36 :: Sweet Syndrome
:: Philip R. Cohen & Razelle Kurzrock
鄭煜彬(20200301)
DEFINITION
|
|
What is the typical features of Sweet
syndrome(SS)?
|
1.
Acute onset of pyrexia &
painful skin lesions
2.
Dense dermal infiltrate of
mature neutrophils
3.
Promptly resolve after
systemic steroids.
|
What are the inflammatory (neutrophilic)
diseases in dermatology?
|
SS, pyoderma gangrenosum, subcorneal
pustular dermatosis, Bowel bypass syn., erythema elevatum diutinum,
neutrophilic eccrine hidradenitis, rheumatoid neutrophilic dermatitis, autoinflammatory
diseases (Schnitzler syn., Blau syn., PAPA syn., SAPHO syn….)
|
EPIDEMIOLOGY
|
|
What is the common onset age & gender
of SS?
|
30-60 y/o, female
|
What is 3 types of SS according to the causes?
|
Classical, malignancy-associated, &
drug-induced
|
CLINICAL FEATURES
|
|
HISTORY
|
|
What is the general appearance of SS?
|
Dramatically ill + fever + skin eruption ± arthralgia,
general malaise, headache, & myalgia
|
What is the time sequence between skin
eruption of SS & fever?
|
Concurrently present with the fever or
follow the fever by several days to weeks.
|
CUTANEOUS FINDINGS
|
|
LESION MORPHOLOGY
|
|
What is the morphology of the lesions of
SS
|
Single or multiple, asymmetrically
distributed, tender, red/purple-red,
papules/nodules with transparent,
vesicle-like appearance (illusion of vesiculation = edema in the upper
dermis)
|
What is the change of lesions of SS in
the later stages?
|
1.
Central clearing→annular or arcuate
patterns (targetoid)
2.
Enlarging→coalesce & form
irregular sharply bordered plaques
|
What is the features of malignancy-associated
SS?
|
Bullous or ulcerated lesions, and/or
mimic pyoderma gangrenosum.
|
What is the result of SS lesions?
|
The lesions resolve without scar.
|
What is the percentage of SS with
recurrence
|
1/3-2/3 of the cases has recurrent
episodes.
|
CUTANEOUS PATHERGY & ISOTOPIC
RESPONSE
|
|
What is the cutaneous pathergy of SS?
|
Skin hypersensitivity at sites of trauma
during the episodes of SS= isotopic (Koebner) response
|
What may induce isotopic response of SS?
|
Wounds, sunburn(phototoxic reaction→photo distributed),
radiation therapy or tattoo
|
What is the Wolf’s isotopic response of
SS?
|
New lesions at the site of another
unrelated & already healed skin disease. (Lymphedematous leg,
postmastectomy arm, & zoster. )
|
What is the other variants of SS?
|
1.
Pustular dermatosis
2.
Neutrophilic dermatosis of
the dorsal hands
3.
Subcutaneous panniculitis
4.
Histiocytoid variant
5.
Giant cellulitis-like variant
|
What is the features of pustular dermatosis of SS?
|
Tiny pustules on the tops of red papules
or erythematous-based pustules. (±ulcerative colitis:)
|
What is the features of neutrophilic dermatosis of the dorsal
hands of SS?
|
1.
A localized, pustular variant
at dorsal hands.
2.
Rapid resolution under steroids
& dapsone.
3.
Concurrent oral mucosa, arm,
leg, back, &/or face lesions.
|
What is the features of subcutaneous panniculitis of SS?
|
1.
Erythematous, tender dermal
nodules on the limbs, mimic erythema
nodosum on the legs
2.
In 80% of SS (not rare).
|
What is the features of histiocytoid variant of SS?
|
1.
Looks like typical SS, but
the dermal infiltrate is composed of “histiocytic” mononuclear cells (presenting immature myeloid cells).
2.
Associated with malignancy
|
What medicine may induce histiocytoid SS?
|
Bortezomib
|
What is the features of giant cellulitis-like variant of SS?
|
1.
Relapsing widespread giant
lesions
2.
F>>M, 48-72 years
(median = 61 years)
3.
Upper leg & buttocks:
most common
4.
Patients are obese (2/3)
& has cancer (1/2)
|
What is the features of necrotizing variant of SS?
|
1.
Rapid onset of edematous,
erythematous, warm lesions→necrotizing fasciitis like lesions
2.
A deep-tissue neutrophilic
infiltration + soft-tissue necrosis.
|
NONCUTANEOUS FINDINGS
|
|
What are the sites of non-cutaneous SS?
|
The bones, CNS/eyes, ears, kidneys,
intestines, liver, heart, lung, mouth, muscles, & spleen/lymph nodes
|
What is the cardiac involvement of SS?
|
1.
Children: postinflammatory
elastolysis (heart & aorta) & Takayasu arteritis. (rare)
2.
Adult: coronary artery
occlusion (rare)
|
What is the CNS involvement (neuro-Sweet
disease, nSd) of SS?
|
1.
Self-remitting/reversible parkinsonism
2.
Eyes: optic nerve involvement
+ panuveitis, endogenous endophthalmitis + chorioretinitis
3.
Radiation therapy-induced nSd
|
What is the oral involvement of SS?
|
1.
Ulcers (in SS with
hematologic disorders, uncommon in classical SS, resolve s/p steroid.
|
What is the otic involvement of SS?
|
Progressive sensorineural hearing loss
|
COMPLICATIONS
|
|
What are the complications of SS?
|
1.
Directly related: secondary
infections (thus antimicrobial therapy is in need)
2.
Indirectly related: inflammatory
bowel disease, sarcoidosis, thyroid dz, & malignancies.
|
What is the meaning of reappearance of
the dermatosis in malignancy-associated SS?
|
Recurrence of the malignancy
|
ETIOLOGY AND
PATHOGENESIS
|
|
ASSOCIATED CONDITIONS
ASSOCIATED DISEASES
|
|
What are the etiologically-related
conditions occur before, concurrent with, or following the diagnosis of SS
|
BRIT.
PRICES: Behçet disease, cancer, erythema nodosum,
infections, inflammatory bowel disease, pregnancy, relapsing polychondritis,
rheumatoid arthritis, sarcoidosis, & thyroid dz
|
What is the “differentiation syndrome”
associated with SS?
|
An inflammatory reaction with↑capillary
permeability, in up to 25% of patients with acute promyelocytic leukemia
treated with all-trans-retinoic acid.(=retinoic acid syndrome)
|
What is the associated conditions of
histiocytoid variant?
|
Medications, autoimmune diseases,
infections & inflammation, inflammatory bowel disease, & malignancy
|
What is the associated conditions of
giant cellulitis-like variant?
|
Obesity & malignancy
|
What is the malignancies in the giant
cellulitis-like variant?
|
Hematologic dyscrasia (multiple myeloma
or myelodysplastic syndrome/myeloproliferative disorder) & breast cancer
|
ASSOCIATED NEUTROPHILIC
DERMATOSES
|
|
What is the characteristic of neutrophilic
dermatoses?
|
An inflammatory infiltrate of mature PMN.
|
What is the associated neutrophilic
dermatoses of SS?
|
Erythema elevatum diutinum, neutrophilic
eccrine hidradenitis, pyoderma gangrenosum, subcorneal pustular dermatosis, &/or
vasculitis.
|
How to differentiate SS & other
neutrophilic dermatoses?
|
According to the location of the lesions.
|
CONCURRENT LEUKEMIA CUTIS
|
|
What are the relationship between SS
& other malignancies?
|
1.
SS exist as a paraneoplastic
syndrome
2.
SS appears with hematologic
disorders concurrently.
|
What is the most frequent hematologic
dyscrasias associated with leukemia cutis (abnormal Nφ) & SS (mature
PMN)?
|
1.
Acute myelocytic leukemia
& acute promyelocytic leukemia
2.
(Less common) myelodysplastic
syndrome, chronic myelogenous leukemia, myelogenous leukemia
|
What are the culprit drugs of SS?
|
All-trans-retinoic acid, bortezomib,
granulocyte colony-stimulating factor (G-CSF), or imatinib mesylate
|
What is the most notorious drug to induce
SS?
|
G-CSF
|
What is the mechanisms of concurrent Sweet
syndrome & leukemia cutis?
|
1.
Secondary leukemia cutis: the
circulating immature myeloid precursor cells are recruited to the
inflammatory oncotactic environment stimulated by SS.
2.
Primary leukemia cutis: the
leukemic cells constitute the bonified incipient, or G-CSF induced
differentiation of atypical leukemia cells into mature Nφ.
|
What is the most threatening associated
disease of SS?
|
Systemic inflammatory response syndrome
(SIRS)
|
PATHOGENESIS
|
|
What is the possible causes of SS?
|
1.
A hypersensitivity reaction
to an eliciting bacterial, viral, or tumor antigen (preceding febrile URI or
tonsillitis, SS with Yersinia enterocolitica improves after antibiotic )
2.
HLA serotypes: non-B54 types
HLA
3.
Cytokines: IL-1, 3, 6, 8, 17,
& TNF-α, IFN-γ, G-CSF & IL-6(MDS-associated SS), GM-CSF (classical
SS), G-CSF (acute myelogenous leukemia-associated SS & neutrophilic
panniculitis)
4.
CD4+ T-cell dysfunction(TH1)
5.
Autoantibodies to
neutrophilic cytoplasmic antigens
|
What disease resemble SS and may share
the same pathogenesis?
|
Familial Mediterranean fever: share the
same mutated gene with chronic myelogenous leukemia associated SS.
|
PHOTOSENSITIVITY
|
|
What drug may induce photodrug-associated
SS?
|
trimethoprim-sulfamethoxazole
|
Why does UV(B) induce SS?
|
1.
UV(B) induces isomorphic(Koebner)
reaction
2.
UV(B) induces Nφ& production of
TNF-α & IL-8.
|
DIAGNOSIS
DIAGNOSTIC CRITERIA
|
|
What is the diagnostic criteria for
classical SS?
|
1
Abrupt onset of painful
erythematous plaques or nodules
2
Hx:
a dense Nφinfiltrate w/o LCV
3
Pyrexia >38°C (100.4°F)
4
Association with an
underlying
4.1
hematologic (AML)
4.2
visceral malignancy (GU organs, breast, & GI), inflammatory dz
(Crohn dz & ulcerative colitis)
4.3
pregnancy
4.4
preceded by an upper respiratory (streptococcosis)
or GI (salmonellosis &
yersiniosis) infection or
vaccination
5
Excellent response to
systemic corticosteroids or potassium iodide(KI)
6
Abnormal Lab values at
presentation (3 of 4): ESR >20 mm/h; CRP(+); >8000/µL leukocytes;
>70% Nφ
|
What is the diagnostic criteria for
drug-induced SS?
|
1, 2, 3 as classical SS
4. Temporal relationship between drug
& clinical presentation, or temporally related recurrence after oral
challenge
5. Temporally related resolution of
lesions after drug withdrawal or tx with systemic steroid
|
SUPPORTIVE STUDIES
|
|
LABORATORY TESTING
|
|
What should we check in SS?
|
CBC/DC(Peripheral leukocytosis +
neutrophilia, -penia in malignancy), ESR/CRP(↑), GOT/GPT(↑), CREA/BUN(↑), urinalysis(hematuria
and proteinuria), thyroid function(hypo- or hyper-), CSF analysis.
|
PATHOLOGY
|
|
What is the features of pathology of SS?
|
A diffuse/dense infiltrate of mature Nφ is present in the
papillary and upper reticular dermis, even in epidermis(spongiosis/subcorneal
pustules) or adipose tissue ± secondary LCV (no fibrin deposition & Nφ in the wall) ± concurrent
leukemia cutis
|
What study should be performed with the
biopsy?
|
Bacterial, fungal, mycobacterial, &
viral culture
|
What is the features of histiocytoid SS?
|
Dermal infiltrate composed of immature
granulocytes (histiocytic mononuclear cells, similar to Nφ but has CD15, 43,
45 (LCA), 68, HAM56, lysozyme, & MAC 387)
|
What cells are contained in the
infiltrate of SS?
|
Nφ(mature or
abnormal), lymphocytes or histiocytes, Eφ(drug-induced or
malignancy-associated)
|
IMAGING
|
|
What image study should be performed in
SS?
|
Brain: PET/CT, CT, MRI, EEG, MRI
Neutrophilic fasciitis/musculoskeletal:
MRI
Pleural effusions: CXR
|
DIFFERENTIAL DIAGNOSIS
|
|
CLINICAL DIFFERENTIAL
DIAGNOSIS
|
|
What are the differential diagnoses of
SS?
|
infectious & inflammatory disorders,
neoplastic conditions, reactive erythemas, vasculitis, Behçet disease, azathioprine
hypersensitivity reaction, chronic atypical neutrophilic dermatosis with
lipodystrophy & elevated temperature (CANDLE) syndrome, &
gemcitabine-associated Sweet syndrome-like eruptions, arthropod bite
|
How to differentiate Behçet disease &
Sweet syndrome?
|
Human leukocyte antigen analysis
B51: Behçet disease; B54: SS
|
What are the differential diagnoses of
giant cellulitis-like SS?
|
Cellulitis & periodic syndromes (such
as familial Mediterranean fever)
|
HISTOLOGIC DIFFERENTIAL
DIAGNOSIS
|
|
How to differentiate SS & leukemia
cutis?
|
Leukemia cutis has malignant immature
leukocytes.
|
How to differentiate SS & neutrophilic
lobular pannicu
litis?
|
SS had infiltratein the lobules, the
septae, or both.
|
What diseases should be differentiate
with histiocytoid SS?
|
Leukemia cutis, interstitial type of
granuloma annulare, interstitial granulomatous dermatitis with arthritis,
& methotrexate-induced rheumatoid papules
|
CLINICAL COURSE AND
PROGNOSIS
|
|
What is the natural course of SS ?
|
Resolves spontaneously, but lesions persist
for weeks to months.
|
What is the course of malignancy-associated
or drug-induced SS?
|
Clearing after successful management of
the cancer or discontinuation of the associated medication.
|
What is the successful management of
tonsillitis, solid tumors, or renal failure-induced SS?
|
Surgical excision or transplantation of
kidney.
|
What patients has higher recurrence of
SS?
|
Malignancy-associated SS.
|
MANAGEMENT
MEDICATIONS
FIRST-LINE TREATMENTS
|
|
What is the first line treatments of SS?
|
Systemic/topical/IL corticosteroids, potassium
iodide & colchicine
|
How to treat refractory SS with steroids?
|
Daily, IV pulse methylprednisolone
|
How to treat localized SS with steroids?
|
Topical (0.05% clobetasol propionate) or IL
(triamcinolone acetonide, 3-10 mg/cc)
|
What is the side effects of KI?
|
Vasculitis & hypothyroidism
|
What is the side effects of colchicine?
|
GI symptoms: diarrhea, abdominal pain,
nausea & vomiting
|
What is the dose of KI tablet?
|
300 mg enteric-coated tablet, 1 tablet
tid (900mg/day)
|
What is the usage of SSKI (saturated solution
of KI, Lugol's solution)
|
1 drop = 0.05 ml
3 drops tid (450mg/day)→↑by 1drop 3 times
each day→7-10 drops tid
(1050-1500 mg/day)
|
What is the concentration of SSKI in SS?
|
1 g KI /ml of water(1 drop = 0.05 ml =
50mg)
|
SECOND-LINE TREATMENTS
|
|
What drugs can be second-line treatments
of SS(4)?
|
Indomethacin, clofazimine, cyclosporine,
& dapsone
|
Which 2 drugs can be used in the
combination therapy with steroids?
|
Cyclosporine & dapsone
|
ANTIBIOTICS
|
|
What are the proper antibiotics used in
the treatment of SS-related infections?
|
Secondarily impetiginized lesions: abx
for S. aureus
Inflammatory bowel disease: metronidazole
Yersinia or Chlamydia: doxycycline,
minocycline,
or tetracycline
|
OTHER AGENTS
|
|
What are other choice of treatments of
SS?
|
l Antineoplastic (azacitidine, chlorambucil, cyclophosphamide, &
rituximab)
l TNF inhibitors (adalimumab, etanercept, infliximab, & thalidomide)
l Miscellaneous: danazol, etretinate, hepatitis therapy, IVIG,
IFN-α, Anakinra(+steroid)
|
MALIGNANCY WORKUP
|
|
Why should we work up malignancies in patients
with SS?
|
Neoplasms concurrently present or
subsequently develop in previously cancer-free SS
|
No comments:
Post a Comment