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3.22 Vasculitides, Vasculopathies, and Other Vascular Disorders
• LFTs ↑, GGT ↑
• Check echocardiogram at diagnosis, 2, 6, and 8 weeks
Treatment
• High-dose ASA (80–100 mg/kg/d) 1 IVIG (2 g/kg)
■
If given within rst 10 days → ↓ coronary artery issues
• Resistant cases: IVIG 1 steroids, cyclophosphamide,
cyclosporine/CIs, plasma exchange, TNF-a inhibitors,
MTX, rituximab, anakinra
• Maintenance: ASA
Key testing facts
• A/w Myocardial infarction (#1 cause of acquired
pediatric heart disease in the United States)
• Patients , 12 months do not respond as well to treatment
Large vessel vasculitis
Subtypes: temporal arteritis and Takayasu’s arteritis
Temporal arteritis (giant cell arteritis)
Epidemiology
• More common in Caucasians, females
• .50 years
Pathophysiology
• Vessel involved: any medium to large vessel (especially
temporal artery)
• Granulomatous vasculitis → ischemia, occlusion,
infarction, and aneurysm
Clinical presentation
• Early: tenderness and erythema along the scalp and
temples with possible cord-like nodule along temporal scalp
■
Other cutaneous symptoms: erythema, purpura,
alopecia of overlying skin, and scalp necrosis
■
Unilateral temporal headache
■
Loss of temporal pulse
■
Jaw claudication
■
Glossitis, necrosis of anterior tongue (lingual artery)
• Late: ulceration or gangrene of frontotemporal scalp or
tongue
• Systemic ndings:
■
Polymyalgia rheumatica (40%–60%) with limb and
girdle muscle pain, stiffness, and weakness
■
Fever and weight loss
■
Neurologic: vision loss (14%), stroke, subarachnoid
hemorrhage, and altered mental status
Pathology
• Segmental granulomatous large vessel arteritis with GCs
• Disruption of media with fragmentation of the internal
elastic lamina
Laboratory workup
• ↑ ESR and ↑ CRP
• Anticardiolipin antibody (may be ↑)
• MRA
• Temporal artery biopsy
Treatment
• ASA 81 mg/day 1 oral steroids (40–60 mg/day)
• Consider methylprednisolone (1 g/day for 3–5 days) if
acute visual loss
• Tocilizimab (anti-IL-6 Ab) approved for large vessel
vasculitis—IL-6 levels may track with disease activity
Takayasu’s arteritis
Epidemiology
• F . M; ,40 years
Pathophysiology
• Vessel involved: aorta and its main branches
• Granulomatous vasculitis → stenosis, occlusion, and
aneurysms
Clinical presentation
• Cutaneous symptoms seen in 50% of individuals,
including:
■
Purpura
■
Erythematous subcutaneous nodules, EN-like lesions,
PG-like lesions
■
Raynaud phenomenon and digital gangrene
• Systemic symptoms:
■
Constitutional symptoms: fever, fatigue, malaise, night
sweats, and weight loss
■
HTN
■
Loss of carotid or radial pulse
Pathology
• Granulomatous inammation of the aorta and its major
branches
Laboratory workup
• ↑ ESR
• MRA with visualization of all branches of the aortic
arch
Treatment
• Oral prednisone (1 mg/kg) for 1 to 3 months with a 6 to
12 month taper
• MTX 15 to 25 mg/wk 1 prednisone
• Cyclophosphamide
• Iniximab or etanercept
• Surgical intervention for cerebral hypoperfusion, valvular
insufciency, and aneurysms
Summary of organ system involvement in various vasculitides (Table 3.49)
Cryoglobulinemias
Epidemiology
• Varies geographically likely related to HCV prevalence
• F . M; average age 5 50 yo
Pathophysiology
• Cryoglobulins are immunoglobulins that precipitate at
colder temperatures; various triggers (Table 3.50)
205
CHAPTER 3 • General Dermatology
Table 3.49 Summary of Organ System Involvement in Vasculitides
Organ System PAN GPA MPA EGPA CV UV HSP
Cutaneous 40%–50% 90%–100%
Pulmonary Rare
Renal 30% 80%–90% 35% 50%
ENT 90% 50%
Musculoskeletal 40%–75%
Neurologic 50%–60% 35% 70%
Gastrointestinal 30% 40%–50% 30% 60%
a
Classic PAN spares the lungs.
CV, Cutaneous vasculitis; EGPA, eosinophilic granulomatosis with polyangiitis; ENT, ear, nose, and throat; GPA, granulomatosis with polyangiitis; HSP, HenochSchonlein purpura; MPA, microscopic polyangiitis; PAN, polyarteritis nodosa; UV, urticarial vasculitis.
a
90% 35% 60%
Table 3.50 Comparison of Cryoglobulinemias
Type Cause Associations
Type 1 (20%–25%) Monoclonal
Mixed cryoglobulinemias
Types 2 and 3
(75%–80%)
immunoglobulin
(IgM » IgG, IgA,
light chains)
Monoclonal
(Type 2) or
polyclonal
(Type 3) IgM
complexes with
polyclonal IgG
Lymphoproliferative disorders
Plasma cell dyscrasia
MGUS
CLL
Multiple myeloma
Waldenström macroglobulinemia
B-cell non-Hodgkin’s lymphoma
HIV
Hepatitis B
Hepatitis C (cutaneous
symptoms more common)
Other infections
Autoimmune disease
SLE (nephritis risk with cryo-
globulins)
Sjögren’s
RA
• Type I: ↑ monoclonal cryoglobulins (IgM . IgG, IgA, light
chains) → complete occlusion of vessel lumens w/ hyaline
material
■
Lacks LCV
• Type II and III (mixed type): complexed immunoglobulins
will precipitate at cooler temperature and occlude vessels
→ triggers complement → LCV
Clinical presentation
• Cutaneous ndings:
■
Type I ndings:
Raynaud phenomenon
Purpura, livedo reticularis/racemosa, ulceration
Cold-induced acrocyanosis of helices
■
Type II and III ndings:
Palpable purpura and urticarial lesions
Systemic ndings common
Pathology
• Type I: occlusive vasculopathy with vessels completely
lled by homogenous hyaline material; lacks LCV
• Types II and III: characteristic features of LCV
Laboratory testing
• ↑ Cryoglobulins
• Complement (hypocomplementemia in 90%; C4 ↓)
• RF (1) (types 2 and 3)
• Hepatitis B/C
• LFTs
Treatment: treat underlying disease
• Type I: treatment of lymphoproliferative disorder (e.g.,
rituximab, bortezomib, lenalidomide); plasmapheresis
(for hyperviscosity symptoms)
• Type II
■
HCV-related: IFN-a 1/– ribavirin; if symptoms severe,
may need rituximab 1 high-dose steroids
■
Other infection: treat underlying infection; steroids if
severe symptoms
■
AICTD: immunosuppression (e.g., rituximab, steroids,
MMF, AXA, cyclophosphamide)
Thrombosis and thrombotic syndromes
• Consider occlusive vasculopathy if livedo reticularis and/
or retiform purpura is present (signs of vascular
occlusion); anatomic distribution can help (Fig. 3.91);
Journal of the American Academy of Dermatology Continuing
Medical Education article on retiform purpura from 2020
is very helpful for workup
• Two broad categories of thrombotic syndromes:
■
Acutely sick patient: disseminated intravascular
coagulation (DIC), purpura fulminans, Coumadin
necrosis, heparin-induced skin necrosis, TTP,
paroxysmal nocturnal hemoglobinuria, HUS,
cholesterol emboli, and septic vasculitis
Purpura fulminans: acute syndrome of progressive
hemorrhagic skin necrosis and DIC; children . adults;
may be idiopathic, triggered by an infection (most
commonly meningococcal, streptococcal,
staphylococcal, or varicella), or due to congenital
deciency in protein C or S; sudden onset of tender
purpura and ecchymosis that often expand rapidly
with a rim of erythema and central hemorrhagic bulla
and/or necrosis; favor acral distribution and buttocks
■
Non-sick patient: APLS, livedoid vasculopathy,
inherited coagulopathies (protein C, S, anti-thrombin
III, Factor V Leiden), and type I cryoglobulinemia
Important subtypes
Calciphylaxis
• Discussed in Section 3.20 and Chapter 10
206
Levamisole
Cryoglobulinemia
Strongyloides
3.22 Vasculitides, Vasculopathies, and Other Vascular Disorders
Angioinvasive fugi
(mucormycosis, aspergillus)
Cholesterol emboli
Bacterial endocarditis
Marantic endocarditis
DIC
Essential thrombocythemia
Chilblains
Purpura fulminans
Cryglobulinemia
Cryfibrinoginemia
Livedoid vasculopathy
Calciphylaxis
Sickle cell disease
DIC
Purpura fulminans
Antiphospholipid syndrome
Hereditary coagulopathy
Fig. 3.91 Anatomic distribution of common causes of retiform purpura. APLS, Antiphospholipid antibody syndrome; CTD, connective tissue disease; DIC, disseminated
intravascular coagulation. (From Georgesen C, Fox LP, Harp J. Retiform purpura: a diagnostic approach. J Am Acad Dermatol. 2020;82[4]:783–796.)
Antiphospholipid syndrome
Cryoglobulinemia
Small vessel vasculitis
Polyarteritis nodosa
Granulomatosis with
polyangiitis
Autoimmune-CTD
Leprosy
■
Epidemiology
• Mainly young women
■
Cholesterol emboli
Bacterial endocarditis
Marantic endocarditis
DIC
Purpura fulminans
Hereditary coagulopathy
a/w SLE (most common) and other autoimmune
conditions including RA and UC
Catastrophic antiphospholipid syndrome (CAPS)
Warfarin induced necrosis
Heparin induced
thrombocytopenia
Ecthyma gangrenosum
Purpura fulminans
Leprosy
APLS
Calciphylaxis
Chilblains
APLS
Cryglobulinemia
Small vessel vasculitis
Essential thrombocythemia
occurs when antiphospholipid syndrome progresses
Pathophysiology
• Unclear etiology—50% primary, 50% with AICTD
(SLE most commonly, up to 23% develop disease over
9 years)
• Associated with immunoglobulins that are reactive with
phospholipids
and results in multiple thrombotic events (e.g.
multiorgan failure, diffuse microthrombosis of
dermal/hypodermal vessels); mortality rate 5 4%
• Precipitants: surgery, meds (HCTZ, OCPs, ACE inhibitors),
malignancies, anticoagulation withdrawal/low INR, and
infection
• Predisposition to thrombosis
Pathology
Clinical presentation
• History of vascular thrombosis (32%), premature birth,
miscarriage (8%), thrombocytopenia, and labile blood
pressure
• Cutaneous features:
■
livedo reticularis (most common nding)
■
Leg ulcers, pseudovasculitis, digital gangrene,
cutaneous necrosis, splinter hemorrhages,
anetoderma, retiform purpura (suggestive of
occlusion)
■
Atrophie blanche
• Systemic features:
■
DVT, PE, stroke, renal infarct, myocardial infarction,
arthritis, and epilepsy
• Occlusion of arteries and arterioles w/ rbin thrombi;
minimal inammation; lacks LCV
Laboratory ndings
• (1) Antiphospholipid antibodies: anti-cardiolipin
antibodies (most sensitive, most commonly positive),
lupus anticoagulant, and anti-b2-glycoprotein I
antibody (most specic)—one or multiple may be
positive
• False-positive syphilis serology
Treatment
• Empiric anticoagulation, anti-platelet agents, and
antimalarial agents in those with concurrent lupus
207
CHAPTER 3 • General Dermatology
Livedoid vasculopathy (atrophie blanche)
Epidemiology
• F . M; mean age of onset 5 45 yo
• Worse in summer
Pathogenesis
• Unknown, but linked to coagulation disorder
Clinical presentation
• Burning pain along the ankle prior to ulceration
• Cutaneous ndings:
■
Purpuric lesions (retiform purpura) progress to painful
and irregular leg ulcers
■
livedo reticularis
■
Atrophie blanche: stellate porcelain-white scar
(Fig. 3.92) at bilateral malleoli and posterior feet
■
Postinammatory hyperpigmentation
• Systemic ndings
■
A/w Hypercoagulable disorders (#1 association)
Hyperhomocysteinemia, Factor V Leiden,
prothrombin mutations, protein C/S deciency,
↑ Factor VIII, antithrombin III deciency,
cryoglobulinemia, cryobrinogenemia, plasminogen
activator/inhibitor mutation
■
a/w Autoimmune conditions (#2 association)
SLE, scleroderma, and APLS
■
a/w Infections (e.g., hepatitis B/C) and
paraproteinemia less frequently
Pathology
• Segmental hyalinization and thrombosis of small
vessels in the upper and mid dermis
• Late stage with epidermal atrophy and hyalinized vessels
Laboratory ndings
• Perform coagulopathy workup and CTD serologies
(cryoglobulins, cryobrinogen, homocysteine, protein
C/S, antithrombin III, lupus anticoagulant,
antiphosphatidylserine, anti-b2 glycoprotein I, ANA,
Fig. 3.92 Atrophie blanche with punched-out ulcer from livedoid vasculopathy.
(Courtesy of Christopher Sayed, MD.)
anti-cardiolipin AB, Factor V mutation, Factor VIII,
plasminogen activator/inhibitor, and prothrombin
mutation); can also consider infectious and paraproteinemia
workup (e.g., Ig levels, immunoxation, SPEP)
Treatment
• ASA
• Dipyridamole
• Pentoxylline
• In recurrent or recalcitrant cases:
■
Anticoagulation (heparin, warfarin, and
rivaroxaban)—best treatment data
■
Oral steroids (e.g., danazol, methylprednisolone,
betamethasone)
■
Sildenal, TPA, PUVA, hyperbaric oxygen, IVIG
reported in limited cases
Other vasculopathies (Table 3.51)
Other vascular disorders
Venous lake
• Small (,1 cm) dark blue soft papules on lips primarily
• Large ectatic vessel seen in dermis
Telangiectasia
• Permanently dilated dermal vessels that appear red
■
Primary:
Spider telangiectasia (can also occur secondary to
↑ estrogen)
Hereditary benign telangiectasia
Angioma serpiginosum
♦ Females , 20 yo
♦ Pinpoint punctate blanching red-purple petechiae
in clusters/patches in serpiginous pattern
typically on one extremity
Unilateral nevoid telangiectasia
♦ Telangiectasias in trigeminal/upper cervical
dermatomes 1/– Blaschko’s lines
♦ Some cases are acquired, secondary to localized
↑ estrogen receptors on vessels
Generalized essential telangiectasia
♦ Typically adult women
♦ Starts on lower extremities and spreads,
involving large areas
Cutaneous collagenous vasculopathy
♦ Large anatomic areas—does not have female
predominance or centripetal spread
♦ Ectatic dermal vessels with thick hyalinized BMZ
surrounding vessels (stain (1) with collagen
IV/PAS-positive)
♦ Not responsive to laser
■
Secondary:
Photodamage, post-radiation (including repeated
uoroscopy), telangiectatic rosacea, involuted
hemangioma, estrogen-related (e.g., liver disease,
pregnancy, hormone replacement therapy, or
OCPs), CS use, AICTDs (e.g., CREST syndrome),
HIV infection (chest), mastocytosis (telangiectasia
208
3.22 Vasculitides, Vasculopathies, and Other Vascular Disorders
Table 3.51 Vascular Disorders Not Otherwise Discussed
Cause Key Features Laboratory Testing and Treatment
Emboli: cholesterol, bacterial or fungal endocarditis, oxalate
Cholesterol emboli
Inammation: pigmented purpura, hypergammaglobulinemic purpura of Waldenström
Pigmented purpura
(capillaritis, PPD)
Hypergammaglobulinemic
purpura of Waldenström
Hemorrhage: trauma, thrombocytopenia, platelet dysfunction, medication (aspirin, steroids)
Other: levamisole-induced vasculitis, Degos disease, Sneddon syndrome, Schnitzler’s syndrome
Levamisole-induced
vasculitis
Degos disease (malignant
atrophic papulosis)
Sneddon syndrome Livedo racemosa and livedoid vasculopathy with labile blood pressure and
p/w livedo reticularis . retiform purpura or gangrene of the distal
extremities and digits. Clinical setting: post-catheterization (hours–days),
thrombolytics (hours–days), anticoagulation (1–2 months); may be febrile,
hypertensive, and/or with altered mental status
Pathogenesis: fragmentation of an atherosclerotic plaque that embolizes
Histology: cholesterol clefts in small vessels
Group of disorders with clustered petechial hemorrhage
Pathophysiology: inflammation of the capillaries with resultant hemorrhage
PPD Types:
Schamberg’s: cayenne-pepper purpura on the lower extremities (esp. shin,
ankles) that can extend; middle-aged to older adults
Purpura annularis telangiectodes of Majocchi: annular patches with
punctate petechiae on trunk and lower extremity in adolescent/young-adult
women
Lichenoid dermatitis of Guogerot and Blum: rust-colored lichenoid pap-
ules and Schamberg-like purpuric lesions in middle-aged to older men
Eczematid-like purpura of Doucas and Kapetanakis : scaly and eczema-
tous petechiae and purpura in middle-aged to older men
Lichen aureus: solitary golden or rust-colored patch on the lower extremities
Linear pigmented purpura: unilateral, linear eruption of yellow-brown
macules, patches, and red-brown purpura; adolescents and children
mainly
Histology: hemosiderin containing macrophages with RBC extravasation, en-
dothelial swelling, and a perivascular lymphocytic inltrate. Guogerot: lichenoid inltrate; Doucas and Kapetanakis: spongiosis and parakeratosis
Crops of burning/stinging petechiae and/or purpura on the lower extremities,
often seen in women. a/w polyclonal gammopathy (IgG and IgA RF), and
CTD (Sjögren’s)
Pathophysiology: unknown cause, likely immune complex-mediated (IgG and
IgA)
Histology: hemorrhage, mild perivascular lymphocytic infiltrate, or LCV
Cocaine may contain levamisole, an antihelminthic agent, which ↑ its
stimulant effects and bulk
It has recently been shown to cause vasculitis/vasculopathy
Presentation: purpura and necrosis of the earlobes (but also nose, cheek,
extremities), LCV-like lesions, ecchymoses, and systemic vasculitis, especially of
the kidney/lung/testes
Histology: thrombotic vasculitis/LCV 1/– vascular occlusion
Crops of small erythematous papules that develop a central depression/
ivory scar, peripheral erythema and surrounding telangiectasias ( atrophie
blanche)
Systemic symptoms include: GI (bowel perforation)
Seen in young and middle-aged men
Pathophysiology: unknown, possible vasculopathy
Histology: wedge-shaped area w/ dermal edema, mucin, sclerosis; vascular
thrombosis
CNS disease (TIA, stroke, dementia), and extracerebral thrombosis. Seen in
young women aged 20–30
Pathophysiology: a/w APLS, vasculopathy or vasculocoagulopathy
Histology: endothelial inflammation; subendothelial intimal smooth muscle
proliferation; partial or complete occlusion of arterioles
Laboratory ndings:
Eosinophilia common
↑ ESR
↑ BUN/Cr
Treatment:
supportive, aspirin, anti-platelet, statins
Treatment: topical steroids for
pruritus,TCIs, PUVA, NB-UVB,
compression stockings, vitamin C 1 rutin
Treatment: aspirin and compression
stockings controversial; avoid triggers,
including alcohol
Laboratory findings:
↑ ABs to p-ANCA (.80%), c-ANCA
(50%), and human neutrophil
elastase
Agranulocytosis
Leukopenia
Treatment:
Resolution once tainted cocaine
stopped, occasionally immunosup-
pressants
Treatment:
No proven treatment
Aspirin 1/– pentoxifylline
↑ Antiphospholipid antibodies
Treatment:
warfarin (INR 2–3)
209
CHAPTER 3 • General Dermatology
macularis eruptiva perstan), carcinoid, and drugs
(CCBs → telangiectasias in sun-exposed areas)
Genodermatoses: Cutis marmorata telangiectasia
congenita, hereditary hemorrhagic telangiectasia,
ataxia-telangiectasia, Klippel-Trenaunay syndrome,
Rombo, Bloom, Rothmund-Thomson, dyskeratosis
congenita, XP, Goltz (within Blaschko’s lines),
prolidase deciency, and hypotrichosislymphedema-telangiectasia syndrome
Erythromelalgia
• Red, painful/burning, edematous, hot distal extremities
(especially lower extremities—feet/lower legs)
• Episodes usually late day/night
• Many cases a/w small ber neuropathy
• Worse with heat/activity; relieved with cooling, classically
“plunging feet into ice cold water”
• Type 1: occurs with thrombocythemia
■
May → ischemic necrosis
■
Histologically see occlusive thrombi
■
ASA and hydroxyurea may be helpful
• Type 2: primary idiopathic
■
May occur in childhood and be familial
SCN9A mutations (Na1 channel subunit mutation
↓ sympathetic neuron activity, and ↑ pain receptor
sensitivity)
■
May treat with sodium channel blockers (e.g.,
mexiletine and ecainide)
• Type 3: occurs with underlying condition (NOT
thrombocythemia)
• Treatment: supportive treatments, capsaicin cream,
amitriptyline-ketamine gel, lidocaine patches or IV,
mexiletine, antidepressants, anticonvulsants (e.g.,
carbamazepine), CCBs, misoprostol, nitroprusside,
prostaglandin E1, rizatriptan, and anesthetic epidural
infusions/lumbar blocks and sympathectomies
• Pediatric red ear syndrome has similar features and may
represent a subtype of erythromelalgia; red scrotum in older
White men may represent a localized type of erythromelalgia
(doxycycline and gabapentin may be helpful)
Livedo reticularis (LR)
• Reticulated vascular pattern that is usually benign
(physiologic), but may be a/w an underlying disorder
(e.g., AICTD or APLS)
■
Physiologic: secondary to vasospastic response to cold
and improves with heat; processes that → ↓ blood
ow to and within skin or ↓ blood draining out of
skin → deoxygenated blood in venous plexus → livedo
appearance
Physiologic type usually with ne complete network
■
Idiopathic/primary LR: persistent arteriole vasospasm
→ persistent LR of lower extremities
■
LR secondary to vasospasm: may be seen with AICTDs
and Raynaud phenomenon
■
LR secondary to vessel wall issues: usually medium
vessel vasculitis (especially cutaneous PAN; also
systemic PAN, cryoglobulinemic vasculitis, vasculitis
secondary to AICTDs); can also be seen in calciphylaxis
■
Livedo racemosa 5 larger branching and incomplete
rings (vs. smaller complete rings of LR)
Seen in Sneddon syndrome, embolic phenomenon,
APLS or other causes of occlusion
■
LR secondary to intraluminal issues: slow blood
ow within vessels (cryoglobulinemia,
cryobrinogenemia, PCV, thrombocytosis, APLS, and
protein C/protein S/anti-thrombin III deciencies)
versus obstruction of vessels (cholesterol emboli,
APLS, heparin/warfarin necrosis, hyperoxaluria, and
livedoid vasculopathy)
■
Other LR causes: amantadine pheochromocytoma, and
reex sympathetic dystrophy
• Biopsy technique: elliptical excisional biopsy from normal
appearing skin in center of net pattern
Angiospastic macules (Bier spots)
• Benign physiologic vasoconstriction → blanched macules
on lower . upper extremities that appear white
• Induced by tourniquet, resolve with tourniquet release
and leg elevation
• Have been reported in pregnancy and cryoglobulinemia
3.23 PANNICULITIDES AND LIPODYSTROPHIES
Erythema nodosum
Epidemiology
• Most common panniculitis, especially women in second
to fourth decades
Pathogenesis
• Delayed hypersensitivity response (Th1 cytokine pattern)
to various antigens
• Idiopathic most common cause, followed by
streptococcal infections (#1 identiable cause), other
infections (bacterial GI infections [Yersinia, Salmonella,
Campylobacter], viral URIs, coccidioidomycosis, TB, and
histoplasmosis), drugs (estrogens/OCPs, sulfonamides,
and NSAIDs), sarcoidosis, and IBD (Crohn’s . UC)
■
Lofgren’s syndrome: type of sarcoidosis w/ EN, hilar
lymphadenopathy, fever, polyarthritis, and uveitis; a/w
good prognosis
Clinical features
• Acute, tender subcutaneous nodules on pretibial areas
(most commonly) bilaterally with overlying erythema to
bruise-like patches
■
Develop over 1 to 2 weeks, then resolve spontaneously
■
New lesions may develop over 1 to 2 months
■
Can be a/w fever, arthralgias, malaise (may precede
cutaneous ndings)
• Chronic forms (subacute nodular migratory
panniculitis/EN migrans) can occur
■
Women mainly; unilateral; migrating centrifugally
expanding nodules (less tender than EN)
■
Usually idiopathic, but may be a/w Streptococcus
infection; treat with SSKI
210
3.23 Panniculitides and Lipodystrophies
Histopathology
• Septal panniculitis with thickening/brosis of septae
• Neutrophils seen particularly in early lesions
• Miescher’s microganulomas: small histiocytic aggregates
surrounding a central stellate cleft; located in SQ fat
septa
• 1/– Thrombophlebitis (more common in EN-like lesions
seen in Behçet’s disease)
Treatment/clinical course
• Lesions last a few days to weeks, then resolve w/o
scarring; recurrences may occur
• Treat underlying medical issue (if identied)
• Options for treatment of EN: bed rest/elevation, NSAIDs,
SSKI, colchicine (especially for Behçet’s-associated EN),
dapsone, TNF-a inhibitors (especially for IBD-associated
EN), and systemic immunosuppressants
• EN a/w improved prognosis of coccidioidomycosis and
sarcoidosis
Alpha1-antitrypsin deciency panniculitis
Pathogenesis
• Alpha
• Various alleles:
• Heterozygotes with one copy of Z or S have mild/
-antitrypsin (serine protease inhibitor made in
1
liver) deciency → dysregulation of immune system and
↑ neutrophils → release of proteolytic enzymes → fat
necrosis
■
M 5 medium (normal quantities of enzyme)
■
S 5 slow (moderately ↓ quantities of enzyme)
■
Z 5 very slow (severely ↓ quantities of enzyme)
moderate deciency (PiMS, PiMZ); most severe dz 5
homozygous for Z allele (PiZZ)
Pathogenesis
• May be a/w TB (erythema induratum of Bazin) or
idiopathic (nodular vasculitis)
■
Tissue culture for mycobacteria usually negative → PCR
tests for Mycobacterium tuberculosis more sensitive
• Likely type IV cell-mediated response to antigen
Clinical features
• Tender, recurrent red-purple nodules and plaques on
calves most commonly
• May ulcerate, drain, and scar
Histopathology
• Lobular and septal panniculitis (Fig. 3.93) w/ neutrophils,
lymphocytes, macrophages, GCs 1 medium vessel
vasculitis (found in connective tissue septa/fat lobules)
■
Main DDx 5 PAN (both affect medium-sized vessels,
but PAN does not have any signicant involvement of
the fat lobules themselves)
• May have caseous or coagulative necrosis 1/– palisading
granulomas
Treatment
• Treat TB if present; otherwise supportive care 1 various
systemic treatments (CS, NSAIDs, tetracyclines, and SSKI)
Pancreatic panniculitis
Pathogenesis
• A/w pancreatic disorders (e.g., pancreatitis, carcinoma,
and pseudocysts)
• Due to hydrolysis of fat by lipase, amylase, and trypsin
■
↑ Serum levels of any (or all) of these three enzymes
are detectable
Clinical features
• Red/bruised tender plaques—lower trunk and proximal
extremities → ulceration/necrosis → oily discharge
• Preceding trauma in one third
• Lesions quite resistant to treatment → permanent
scarring/atrophy
• A/w chronic liver dz (cirrhosis), emphysema,
pancreatitis, membranoproliferative glomerulonephritis,
c-ANCA vasculitis, and angioedema
Histopathology
• Lobular or mixed panniculitis w/ neutrophils
• Liquefactive necrosis of SQ fat (lobules and septa) and
dermis
Treatment
• ToC 5 alpha1-antitrypsin replacement → rapid
improvement
• Other treatments: doxycycline, colchicine,
cyclophosphamide, dapsone, ↓ alcohol consumption,
plasma exchange, and liver transplant
Erythema induratum/nodular vasculitis
Epidemiology
• Women primarily; 30 to 40 years old
Clinical features
• Subcutaneous nodules of legs (most common site)
■
May occur prior to knowledge of pancreatic issues
■
Lesions are red/brown, rm, and tender → may
ulcerate and release oily discharge
Fig. 3.93 Nodular vasculitis: vascular involvement as seen in this eld is a characteristic feature. (Courtesy of Olayemi Sokumbi, MD.)
211
CHAPTER 3 • General Dermatology
• May have concurrent systemic symptoms:
■
Schmid’s triad (nodular lesions 1 polyarthritis 1
eosinophilia) → a/w poor prognosis
Histopathology
• Mixed panniculitis w/ “ghost cell” (anucleate necrotic
adipocytes) formation and fat necrosis w/ saponication
by calcium salts → basophilic color of damaged fat
lobules
Treatment
• Treat underlying pancreatic disorder
Lipodermatosclerosis
Epidemiology
• Middle-aged/elderly
• F . M
Pathogenesis
• Due to combination of venous insufciency and
brinolytic abnormalities → ↑ capillary permeability
→ brinogen leakage → brin cuffs form around vessels
→ ↓ O
dermal stasis changes
Clinical features
• Acute (rubor, dolor, and calor) → chronic (well-dened
induration, hyperpigmentation, “inverted wine bottle”
appearance from sclerosis)
• Medial lower leg, superior to malleolus
Histopathology
• Septal thickening (Fig. 3.94) and brosis, cystic fat
necrosis w/ surrounding lipophages (histiocytes that
have engulfed lipid from necrotic lipocytes), mild nonspecic inammation, lipomembranous change, 1/–
signs of stasis changes (angioplasia, inammation, and
brosis)
exchange/tissue anoxia → cystic fat necrosis 1/–
2
Treatment
• Leg compression and elevation 1/– IL steroids
• Systemic options: danazol, oxandrolone, pentoxifylline,
horse chestnut extract, tetracylines, HCQ
Panniculitis secondary to external factors
• Cold panniculitis: acute, rm, painful, cool (in temperature),
and erythematous plaques/nodules that develop 1 to 3 days
post cold exposure; most commonly affects areas of
prominent fat distribution (central cheek, thighs, and back)
■
Named variants:
Popsicle panniculitis: seen in infants mainly on
cheeks (due to higher saturated:unsaturated fatty
acid ratio)
Equestrian panniculitis: young women equestrians
on thighs
■
In neonates, risk factors include head or whole body
hypothermia for hypoxic-ischemic encephalopathy and
use of ice therapy for supraventricular tachycardia
■
Histology: lobular panniculitis 1 typical pernio
changes (supercial and deep PV/peri-eccrine
lymphohistiocytic inltrate w/ papillary dermal edema)
■
Resolves over several weeks; lipoatrophy may develop
in affected areas
• Physical trauma/foreign material:
■
Sclerosing lipogranuloma: male genitalia (penis
mainly) due to injection of oil-based materials for
augmentation
■
Other injectable agents (e.g., factitial, cosmetic)
■
Blunt trauma
■
Histologic clues: vacuolated spaces, foreign material
(e.g., “Swiss cheese” appearance in sclerosing
lipogranuloma), and evidence of needle stick injury
Lipodystrophies
• Disorders with selective loss of fat 1/– fat accumulation
in other areas (Table 3.52)
Fig. 3.94 Lipodermatosclerosis (sclerosing panniculitis) close-up view of microcysts. (Courtesy of Olayemi Sokumbi, MD.)
212
3.24 DERMATOSES OF PREGNANCY
Physiologic changes during pregnancy
• Vary widely, but most notable are linea nigra, melasma,
telogen efuvium (TE), striae gravidarum, and palmar
erythema
Dermatoses of pregnancy (Table 3.53)
3.25 HAIR, NAIL, AND MUCOSAL DISORDERS
Non-scarring alopecia
Androgenetic alopecia
Epidemiology
• 80% men and 50% women by age 70
3.25 Hair, Nail, and Mucosal Disorders
Table 3.52 Lipodystrophies
Disorder Pathogenesis Clinical Features Other Facts
Congenital generalized
lipodystrophy
(Berardinelli-Seip
syndrome)
Familial partial
lipodystrophy
(Köbberling-Dunnigan
syndrome)
Acquired generalized
lipodystrophy (Lawrence
syndrome)
Acquired partial
lipodystrophy (BarraquerSimons syndrome)
Autosomal recessive
AGPAT2 (type 1), BSCL2/
seipin (type 2), CAV1
(type 3)
Highest frequency in Brazil
Autosomal dominant
LMNA, PPARg (milder clin-
ical features but worse
metabolic features),
AKT2, PLIN1
Unknown Loss of fat on face, trunk, extremities (in-
Sporadic vs. autosomal
dominant
LMNB2
Linked to infections and
autoimmune diseases
Loss of fat in face (e.g., preauricular),
trunk, extremities, viscera 1/– palmoplantar/retro-orbital/tongue/breasts/vulva/periarticular ((–) in type 1 and 3, (1) in type 2)
Acanthosis nigricans, hypertrichosis, xan-
thomas
Muscular hypertrophy appearance
Osteosclerotic and lytic skeletal changes
Masculinization in women/enlarged genita-
lia in kids only
Starts at birth
Loss of fat on extremities/buttocks
1/– trunk (anterior . posterior)
↑ Fat on face/neck, labia majora
Muscular hypertrophy appearance w/
prominent veins
Starts at puberty
Tuberous xanthomas, acanthosis nigri-
cans, hirsutism
cluding palms/soles)
Loss of visceral fat but bone marrow fat
preserved (unlike congenital general-
ized lipodystrophy)
Muscular appearance due to loss of fat
Acanthosis nigricans, hyperpigmentation,
eruptive xanthomas, hirsutism
Starts in childhood/adolescence (7 yo in
panniculitic variant, 15 yo in autoim-
mune variant, 20yo in idiopathic variant)
F » M
Loss of fat on face (cadaveric facies),
upper extremities, trunk (spreads in
cephalocaudal direction, sparing lower
extremities
↑ Fat in hips, legs, gluteal region
Acanthosis nigricans, hirsutism
starts in childhood/adolescence
Diabetes/insulin resistance more common, including
metabolic syndrome
↑ Triglycerides
↓ HDL
Vitamin D resistance in type 3
PCOS, infertility (women)
Hypertrophic cardiomyopathy (usually fatal—
mean lifespan 5 32 yo; ↑ in type 2), atherosclerosis, liver failure, fatty liver/cirrhosis, organomegaly,
acute pancreatitis, proteinuric nephropathy,
developmental delay (↑ in type 2)
Diabetes/insulin resistance more common
↑ Triglycerides
↓ HDL (worse w/ PPARG type)
Acute pancreatitis, fatty liver/cirrhosis, menstrual is-
sues, PCOS, atherosclerosis, HCM
Worse in women
subtype with mandibuloacral dysplasia (LMNA or
ZMPSTE24 mutation)
Diabetes/insulin resistance more common
↑ Triglycerides
↓ HDL
30% have preceding AICTD (type 2 variant; e.g.,
juvenile DM) or infection, and one fourth have pre-
ceding panniculitis (type 1 variant)
Clitoromegaly, PCOS, menstrual issues
Coronary artery dz, PVD
Organomegaly
Fatty liver/cirrhosis (can be fatal, more so than in
congenital generalized lipodystrophy)
Cirrhosis, proteinuric nephropathy
↑ Triglycerides and DM2/ insulin resistance may
occur but metabolic syndrome less common than
other disorders
may be preceded by infection and/or a/w AICTD
(SLE, DM)
Menstrual issues
Membranoproliferative glomerulonephritis
(several years after lipodystrophy, present in 20%
of pts)
↓ C3 and ↑ C3 nephritic factor (polyclonal IgG;
binds C3) → activates alternative complement
pathway → adipocyte death and ↑ Neisseria
meningitides infections
Table 3.53 Dermatoses of Pregnancy
Disorder Onset Appearance Treatment/Course Risk to Fetus Interesting Facts
Pemphigoid
gestationis (herpes
gestationis)
Polymorphic
eruption of
pregnancy
Typically second
or third
trimester or
immediately
postpartum
Third trimester
or immediately
postpartum
Pruritic papules/plaques that →
blisters/bullae mainly on trunk
(does NOT spare umbilicus)
Urticarial, pruritic papules/
plaques which prefer striae
distensae (spares umbilicus)
Usually spares face/extremities
Topical or systemic corti-
costeroids depending
on severity (taper once
blisters resolve)
Spontaneously resolves
but may are/recur
around delivery, with
menstruation, or OCPs
May take weeks to
months after delivery to
entirely resolve
Typically recurs in future
pregnancies (more
severe/earlier)
Resolves over 4 weeks
Topical steroids and anti-
histamines may help
Typically does not recur
↑ Risk prematu-
rity and SGA
Baby may have
mild transient
pemphigoid lesions
Risks to fetus cor-
relate with dz
severity
None Mainly seen in primipa-
May occur with chorio-
carcinoma
↑ Risk of Graves’ dis-
ease
Due to IgG1 autoanti-
bodies against BP180
NC-16A segment (DIF
with linear C3 along
perilesional BMZ)
Strongly a/w HLA-DR3
and DR4
rous women
↑ Risk in multiple-ges-
tation pregnancies
Continued
213
CHAPTER 3 • General Dermatology
Table 3.53 Dermatoses of Pregnancy—cont'd
Disorder Onset Appearance Treatment/Course Risk to Fetus Interesting Facts
Intrahepatic
cholestasis of
pregnancy
Atopic eruption
of pregnancy
(prurigo of
pregnancy)
Pustular psoriasis
of pregnancy
(impetigo
herpetiformis)
SGA, small-for-gestational age
Third trimester Extreme generalized pruritus
Usually first
or second
trimester
Usually third
trimester
without primary rash
Worse at night
Bad on palm/sole
Excoriations/ prurigo typically
seen on extensor surfaces
Jaundice in 10%
Eczematous or papular eruption
usually in typical sites (e.g.,
exural surfaces) typically in
patients with atopic history
May be are of pre-existing der-
matitis or rst time they have
had dermatitis (80%)
Generalized pustular psoriasis
starting in flexures (groin mainly)
MUST ↓ serum bile acid
levels—oral ursode-
oxycholic acid
May recur in future preg-
nancies and can are
with OCPs
May have steatorrhea
and vitamin K deciency → postpartum
hemorrhage
Pruritus resolves shortly
after delivery
Treatments: topical ste-
roids, emollients, antihistamines, UVB for
symptom control
Usually recurs with future
pregnancies
Supportive, prednisone
Resolves with delivery
typically
Recurs with future preg-
nancies and OCPs
↑ Risk of prema-
ture birth, intrapartum fetal
distress, stillbirth
Risks correlate with
bile acid levels
(i.e., .40
mmol/L)
None
Placental
insufciency,
stillbirth,
neonatal death
in bad disease
↑ Total serum bile acid
levels (.11 mmol/L)
due to ↓ excretion
Most have ↑ IgE
May be Th2-mediated
Most common pruritic
disorder of pregnancy
A/w Hypocalcemia and
↓ vitamin D
Mom may have cardiac/
renal failure
Pathogenesis
• Strong genetic predisposition (polygenic)
• In men, ↑ DHT expression plays a role
■
5a-reductase enzymes catalyze conversion of
testosterone to DHT:
Type I 5 a-reductase—skin, hair follicles, and
sebaceous glands
Type II 5 a-reductase—prostate mainly, but also
hair (inner root sheath)
♦ Absence prevents male AGA
Clinical features
• Norwood-Hamilton classication system in men
■
Progressive frontotemporal hairline recession and
thinning over frontal crown and vertex scalp
• Ludwig scale in women
■
Preservation of frontal hairline with progressive
thinning from vertex to frontal scalp
■
Increased central part width creates “Christmas tree
pattern”
Histology
• ↑ Vellus hairs and miniaturized hairs (both types are
ne, short, non- or lightly pigmented)
■
Vellus hairs: have always existed as small hairs (never
were terminal hairs)
■
Miniaturized hairs: hairs that were previously large
terminal hairs but have shrunk over time to become
small hairs roughly the size of vellus hairs
• ↓ Terminal hairs (thick, long, and deeply pigmented)
■
Due to progressive miniaturization process
• Anisotrichosis: ↑ variability in hair shaft size
■
Due to progressive process of terminal hairs becoming
“miniaturized” to resemble native vellus hairs
■
This nding is a very helpful clue on horizontal sections
• Shortened anagen phase → slightly ↑ telogen:anagen
ratio (“catagen/telogen shift”)
■
Degree of catagen/telogen shift is mild in androgenetic
→ not nearly as dramatic of a catagen/telogen shift as
in AA or trichotillomania/traction alopecia
• ↑ Fibrous streamers: bromucinous tract remnants
underneath miniaturized or telogen hairs
■
↑ Streamers are a helpful clue that suggests one of two
processes:
Hairs are undergoing miniaturization process
(transforming from a robust terminal hair → wispy
vellus-like hair)
Hairs are cycling more rapidly from anagen phase
→ telogen phase (“catagen/telogen shift”)
Both processes contribute to the ↑ in brous
streamers seen in AGA
■
Note: ↑↑ brous streamers are also seen in AA and
trichotillomania/traction alopecia
In these diseases, the massive catagen/telogen shift
is primarily responsible for the dramatic increase in
streamers
Treatment
• Only minoxidil and nasteride are FDA approved for AGA
■
Topical minoxidil 2% or 5% (5% is more effective)
Lengthens anagen phase and ↑ blood ow
Regrowth most effective on vertex scalp (. frontal
scalp); takes at least 4 months and must be
continued indenitely for hair retention
■
Finasteride 1 mg/day (type II and III 5a-reductase
inhibitor)
Only approved for use in males but higher doses
(2.5–5 mg/day) may help women
214