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48
(MMP) C3 to the basement membrane zone (BMZ) anti-
laminin 5 (epiligrin) “ less frequent.
Bullous systemic lupus Type VII collagen. Generalized or acrolocalized vasculitis (4“30%),
49
erythematosus (SLE) livedo reticularis (22“35%), and alopecia
(38“78%) frequently seen.
Lichen planus pemphigoides BP 180 (type XVII collagen) at a C-terminus of
(LPP) NC16A that is not targeted by BP or PP sera.
II. Mutations of the basement membrane zone proteins
Epidermolysis bullosa Keratin mutations.
junctionalis
Epidermolysis bullosa Keratin mutations.
dystrophicans (Hallopeau- Autosomal recessive.
50
Siemens)
III. Metabolic disorders
Porphyria cutanea tarda51 Caterpillar bodies (eosinophilic, elongated, Can be triggered or worsened by pregnancy.
segmented bodies located within the roofs of
blisters) are specific for porphyrias.
IV. Drug-induced
Toxic epidermal necrolysis Reported in pregnancy after heparin, tocolytics,
(Lyell syndrome/Stevens- methotrexate, etc. Also reported in association
52,53
Johnson syndrome) with staphylococcal infections.

Table modified and classification from Megahed, M. Histology of subepidermal bullous dermatoses. Verh. Dtsch. Ges. Pathol. 1996; 80: 223“8.
IgG ¼ Immunoglobulin G; IgA ¼ Immunoglobulin A
a
Collagen is synthesized as procollagen and large extra domains known as propeptides are cleaved off enzymatically. Bullous pemphigoid antigen 180
(BP180, type XVII collagen) is a transmembrane glycoprotein that spans the lamina lucida of the dermal“epidermal junction. This glycoprotein™s
ectodomain consists of 15 interrupted collagen domains. The largest noncollagenous (NC) domain (NC16A) is located adjacent to the cell membrane
and is the frequent target site in many subepidermal bullous dermatoses.



Scattered reports of cutaneous neonatal herpes gestatio- steroids for mild cases and systemic oral steroids for more severe
nis57,58,59,60 have shown the frequency of skin lesions in newborns cases.
of mothers with pemphigoid gestationis to be about 5“10% with
Anesthetic implications
most cases resolving after only local antiseptic therapy. The goal
of therapy is to limit blister formation, secondary infection, and Care should be taken to avoid sites with blisters as they can easily
scarring. Symptomatic treatment consists of potent topical be damaged leading to secondary infection and/or scarring.



348
Chapter 19


However, as PP does not represent an infectious process, areas of hypocalcemia in patients with pustular psoriasis have included
skin with mild disease can be utilized for invasive procedures. hypoparathyroidism, hypovitaminosis D, malnutrition, oral con-
traceptive use,65 and severe hypoalbuminemia.66 Lesions of PPP
Unlike the situation in MMP, the airway is not involved in PP so
special precautions are not needed. Dapsone is sometimes used are expected to disappear after birth but may recur during peri-
in the treatment of PP and has been associated with severe ods of stress and during subsequent pregnancies at an earlier
methemoglobinemia and fetal hypoxia61,62 as well as hemolytic gestational age. Fetal concerns in PPP are related to placental
anemia, especially in patients with glucose-6-phosphate dehy- insufficiency, which may be found even when the disease is
drogenase deficiency.63 controlled with corticosteroids. The placental dysfunction may
increase the risks of stillbirth.
Medical management of PPP includes the administration of
Pustular psoriasis of pregnancy (impetigo
steroids, antibiotics (for secondary infection), and the correction
herpetiformis)
of hypocalcemia. In cases where steroids have been inadequate,
This rare pustular dermatosis is noninfectious and thus the term various immunomodulators, e.g. cyclosporine A, have been used.
pustular psoriasis of pregnancy (PPP) is preferred to ˜˜impetigo Lesions often return, particularly if hypocalcemia recurs.
herpetiformis.™™ Pustular psoriasis of pregnancy usually occurs Postdelivery, persistent disease is treated more aggressively
during the third trimester of first pregnancies64 and is character- with photochemotherapy, including the synthetic retinoids
ized by an acute eruption of erythematosquamous plaques cov- etretinate and isotretinoin. The toxicities associated with both
ered with tiny superficial pustules in a herpetiform distribution short- and long-term treatment with oral retinoids include muco-
(see Figure 19.2). Mucous membrane involvement is less likely. cutaneous effects, adverse modulation of serum lipid levels,
Lesions are accompanied by fever and first appear in the skin elevation of liver enzymes, and after long-term chronic dosing,
folds of the groin and under the breasts. The face, scalp, hands, skeletal and ligamentous calcification, and hyperostosis. Both
and feet are often spared, although painful oral and esophageal etretinate and acitretin, like all retinoids, are known teratogens
erosions have been reported.28 Pustular psoriasis of pregnancy in animals and humans. Consequently, women of childbearing
can be associated with marked constitutional symptoms such as age are strongly advised to avoid pregnancy during treatment
fever, chills, nausea, vomiting, diarrhea, malaise, and arthralgias. and up to five years following cessation of therapy with etretinate
and the carboxylic acid metabolite, acitretin.67
Secondary infection may complicate the rash.
The etiology of PPP is unclear but may be related to decreased
Anesthetic implications
levels of skin-derived antileukoproteinase (SKALP). Skin-derived
antileukoproteinase is a strong and specific inhibitor of human The anesthesiologist should evaluate the extent of the lesions,
leukocyte elastase (HLE) and proteinase 3, two neutral protein- including the presence of mucosal lesions or secondary skin infec-
ases that have been implicated in leukocyte migration and tissue tion. The possibility of esophageal lesions should be considered
destruction. Pustular psoriasis is often a manifestation of hypo- when placing orogastric tubes. Lesions should be avoided during
calcemia and therefore patients with PPP should be tested for invasive procedures, e.g. neuraxial blocks. The timing and effect-
maternal hypocalcemia, which when severe may lead to delir- iveness of prior treatment and laboratory evaluations should
ium, convulsions, and tetany. Various reported causes of guide the need for supplemental steroids and calcium therapy.


Figure 19.2 Impetigo herpetiformis. # Bernard
Cohen, MD, Dermatlas: www.dermatlas.org. Used
with permission. (See color plate section.)




349
5 Other disorders


Although severe calcium deficiency is rare, the preoperative reported infrequently and general anesthesia is commonly used.
correction of hypocalcemia with intravenous administration of Various authors have summarized the special anesthetic consid-
erations for patients with EB.90,91,92,93 Optimal positioning of the
10“20 ml of 10% calcium gluconate over 1“2 min, followed by an
infusion of 10 ml of 10% calcium gluconate in 500 ml of solution patient to avoid pressure points or tangential friction is necessary.
over six hours has been recommended by Roizen.68 As respiratory Avoid scrubbing of the skin and subcutaneous infiltration, surgical
alkalosis decreases serum levels of ionized calcium, effective tape, and adhesive electrodes. The eyes should be lubricated but
analgesia should be used during labor and normocarbia should not taped. Electrocardiographic monitoring using leads placed
be maintained during controlled ventilation. Hypocalcemia may over sheets with water as the conductive media has been
described.94 Skin beneath a blood pressure cuff must be protected
delay ventricular repolarization and prolong the QT interval.
by adequate padding, and maximum intervals between measure-
ments should be chosen. Nasal, oral, laryngeal, and tracheal
Other dermatologic diseases and pregnancy
manipulations should be kept to a minimum for protection of the
Ehlers-Danlos syndromes (Table 19.6) upper airway. Fiberoptic intubation is preferred because of the
possibility of microstomia and the simultaneous direct examina-
The Ehlers-Danlos syndromes (EDS) are a heterogeneous group
tion of the airway for lesions. In addition, oro- and/or nasopharyn-
of rare inherited connective tissue disorders that are character-
geal tubes and catheters should be avoided. With care, serious
ized by joint hypermobility, skin fragility, easy bruising, and
complications did not occur in 67 procedures using standard anes-
hyperextensibility.69,70,71,72,73,74,75,76,77,78,79,80,81,82 For a compre-
thetic techniques, including general and regional anesthesia.93
hensive discussion of EDS the reader is referred to Chapter 8.


Erythema multiforme, Stevens-Johnson
Epidermolysis bullosa
syndrome and toxic epidermal necrolysis
Epidermolysis bullosa (EB) is a rare inherited disease marked by
(Lyell syndrome)
fragile skin and debilitating recurrent bullae or blister formation
Erythema multiforme (EM) is an acute, sometimes recurrent,
following minimal mechanical trauma. The defect is in the genes
inflammatory disease of the skin and mucous membranes.
regulating keratin formation and at least 18 different mutations
occur, all of which produce a fragile cell phenotype.83 At least ten Erythema multiforme minor describes cases of typical target
lesions, lacking mucosal involvement, and constitutional symp-
of these mutations lead to EB. Dystrophic nails and flexion con-
toms of fever, malaise, and arthralgias. Erythema multiforme
tractures of the joints can lead to deformities. Carious teeth are
major is a far more serious and potentially life-threatening
common, and microstomia caused by scarred contractures of
disease with mucosal lesions and occasional multisystem invol-
the lips may complicate intubation. Ocular, gastrointestinal,
vement. Erythema multiforme is manifested as purpuric vesicu-
genitourinary, and musculoskeletal complications have been
lobullous target lesions accompanying macules, papules, and an
described. All types of EB have variable expression, which
urticarial-appearing rash. The lesions may occur on any part of
accounts for a broad range of clinical presentations. The most
the body and may arise suddenly, lasting one to four weeks.
severe forms of EB include the recessive dystrophic EB (RDEB),
Target lesions show necrotic keratinocytes, dermal endothelial
junctional EB (JEB), EB with pyloric atresia (EB-PA), and EB
simplex (EBS).84 DNA-based prenatal diagnosis is available and swelling, and papillary edema. Stevens-Johnson syndrome (SJS)
and toxic epidermal necrolysis (TEN) are similar diseases, but
genetic counseling is usually offered. Treatment is symptomatic
they generally involve more extensive skin involvement than EM
for most types although high-dose intravenous immunoglobulin,
with potentially high mortality rates.95,96,97 Patients with SJS may
immunosuppressants, and steroids are used in a similar disease,
develop large bullae with ulcerated erosions of the nose, mouth,
epidermolysis bullosa acquisita. Aggressive squamous cell carci-
and tracheobronchial tree. The conjunctiva, gastrointestinal
noma occurs frequently, particularly in patients with severe dys-
trophic EB.85 Pregnancy rarely affects the course of EB. mucosa, and genitourinary mucosa may be involved, leading
to stenoses, including vaginal stenosis. Bacterial secondary infec-
Anesthetic considerations tions are common. Serious, but rare, complications include hepa-
Anesthesia for pediatric and young patients with EB has been titis, glomerulonephritis, cardiac involvement, and pneumonia.
described in many reports.86,87,88,89 Airway complications are Fluid and electrolyte imbalance and anemia may occur. Toxic


Table 19.6 Regional obstetric anesthesia in Ehlers-Danlos patients (see also Chapter 8)

Type of anesthesia Procedure Comorbid conditions Maternal outcome Fetal outcome References

Single-shot spinal Cesarean section Mitral valve prolapse; breech Good Good 70,71,79,82
Epidural Labor and vaginal delivery History of vertebral artery Good Good 80,82
dissection
Combined spinal epidural Cesarean section Good Good 81
Caudal Labor Good Good 82




350
Chapter 19


epidermal necrolysis is defined by the presence of more extensive interlobular septa, and small vessels. This stage is followed by a
detachment of skin (>30%). chronic lymphocytic septal infiltration and eventually, in rare
Both EM major and SJS can involve internal organs. Erythema cases, a noncaseating granuloma. A histopathologic hallmark of
multiforme minor usually follows recurrent herpes simplex infec- erythema nodosum is the presence of the so-called Mieschers
tions and tends to be self-limiting. Erythema multiforme major is radial granulomas, which consist of small, well-defined nodular
mainly related to herpes virus infection whereas precipitating aggregations of small histiocytes arranged radially around a
central cleft of variable shape.102 Due to its association with
factors of SJS and TEN include drug reactions (barbiturates, anti-
biotics, nonsteroidal anti-inflammatory agents, salicylates, anti- tuberculosis, a skin test for tuberculosis and a chest radiograph
convulsants, and digitalis)98 and herpes simplex virus (HSV), are indicated. The ionizing radiation from a chest radiograph is
mycoplasma, human immunodeficiency virus (HIV), bacterial 5“10 mrads ($0.1 mGy), which is less than 5% of the maximal
(especially Staphylococcus), fungal, and parasitic infection. recommended exposure in pregnancy. The fetus should none-
Stevens-Johnson syndrome may also be a manifestation of theless be protected by abdominal shielding.
collagen-vascular or neoplastic disease.
Anesthetic considerations
Erythema multiforme occurs primarily in young healthy per-
The presence of erythema nodosum should lead to an investigation
sons. Although mortality in SJS is between 3% and 18%, SJS may
of its etiology, with particular attention to infection, sarcoidosis, or
well have its ominous prognostic connotation more as a result of
underlying inflammatory bowel disease (Sweet syndrome).103
inadequate treatment than as a result of the inherent clinical
Steroids are generally avoided. Needle placement should consider
disease. High-dose systemic steroid therapy (oral dosage starting
the possibility of local infection although reactive areas (nodules)
at >80 mg/day) will usually resolve most cases of SJS.
are generally not infected. Overall, any anesthetic technique is
generally acceptable.
Anesthetic considerations
Erythema multiforme and SJS, like all subepidermal bullous
dermatoses, must be managed with extreme caution with regards Sweet syndrome
to possible airway lesions and with meticulous care to avoid
This acute febrile neutrophilic dermatosis is often associated with
friction over involved skin. Specific guidelines for anesthetic care
myelodysplastic syndromes, hematologic malignancies, or inflam-
are similar to those discussed above for epidermolysis bullosa.
matory bowel disease, but also has been related rarely to pregnancy,
autoimmune disorders, and drug therapies. In addition to skin
Erythema nodosum manifestations (painful erythematosus plaques that histologically
show a dense dermal infiltrate of neutrophils),104 there may be
Erythema nodosum, the most frequent variant of the panniculi-
significant pulmonary involvement with respiratory compro-
tides, often follows infection with tuberculosis, leprosy, strepto-
mise.105 Treatment includes corticosteroids and other immuno-
coccus or coccidioidomycosis, sarcoidosis, inflammatory bowel
suppressants. Spinal anesthesia for delivery has been described.106
disease, or malignancies. An association with antiphospholipid
antibody syndrome has been suggested.99 When seen in preg-
nancy, it usually occurs during the first trimester and is not Malignant melanoma
thought to affect the course of pregnancy or the fetus. The disease
The estimated incidence of cancer complicating pregnancy is
is characterized by a prodrome of arthralgia, fever, chills, malaise,
about 1 per 1 000 pregnancies, with malignant melanoma among
and, rarely, abdominal pain, followed by the appearance of
the top five cancers affecting pregnant women.107 Melanoma inci-
inflammatory tender red nodules on the extensor (anterior) sur-
dence rates are increasing dramatically and melanoma is now a
faces of the lower extremities. The nodules may become multiple
major cause of cancer death in women of childbearing age. Due
and plaques may appear on the trunk, arms, neck, and face.
to changes in pigmentation during pregnancy, the diagnosis of
Although the nodules do not ulcerate, they do transform from
malignant melanoma during pregnancy is more difficult.108
red to a livid violet, then yellow as a bruise, during the three- to
Nonetheless, the characteristic ABCDE markings (see Table 19.7)
six-week course of the disease. The lesions heal without scarring
help differentiate melanoma from the expected hyperpigmentation
or atrophy. Rarely, the disease may persist for years. Aseptic joint
of nevi that occurs during pregnancy. The suspicion of melanoma
swelling may also occur, particularly in association with lower
is an indication for immediate excisional biopsy. Pregnancy itself
extremity edema. Erythema nodosum occurs primarily in women
is not thought to affect the prognosis of the disease.109,110 Rather,
(female:male ratio of 6:1).100,101 Overall, it is an uncommon clin-
ical diagnosis. The average dermatologist will likely see few cases
during his or her professional lifetime. Usually, erythema nodo- Table 19.7 Markings of cutaneous melanoma
sum is a benign self-limiting clinical entity that requires little
A Asymmetry
supportive therapy and no aggressive diagnostic work-up. The
B Border irregularity
major exception is the patient with erythema nodosum who is
C Color variation or dark black color
febrile and cachectic. The diagnosis of erythema nodosum may
D Diameter greater than 0.6 cm
be confirmed early in the disease process with a deep incisional
E Evolving behavior (rather than static lesion)
biopsy, which will show neutrophils in the subcutaneous fat,



351
5 Other disorders


the most important factor influencing the prognosis of melanoma
Table 19.8 Signs and symptoms of neurofibromatosis type 1
is the stage of the disease at the time of diagnosis. Risk factors for
(see also Chapter 8)
melanoma include a positive family history, white race, light com-
plexion, increased numbers of nevi, and a tendency to sunburn.111 CNS Seizures, headaches, brain tumors, brain
Melanoma is the cancer most likely to metastasize to the placenta vascular defects, learning disabilities, mental
and fetus. Alexander and colleagues112 reported that cases of pla- retardation, macroencephaly, cancer,
cental and fetal metastasis, from any tumor source, are extremely Chiari I malformation125
rare. They found that the fetus was affected in only 17% (15 of 87) Ophthalmic Visual impairment/blindness, optic glioma,
of women who had placental tumor involvement. Forty percent of Lisch nodules (benign iris hamartomas)
cases involving the fetus (6 of 15) were due to melanoma.112 Laryngeal Speech impairments and delays
Skin Caf´ -au-lait spots and/or neurofibromas
e
Anesthetic considerations of varying sizes may occur anywhere.
Preoperative assessment should focus on a review of systems to Freckling where skin meets skin (armpits,
determine organ involvement and also, on the particular thera- groin, under breasts), intense pruritus
pies the patient has received. Although localized disease is of little Cardiovascular Hypertension, vessel fragility and rupture,
importance to the anesthesiologist, melanoma may metastasize coagulopathy
to multiple organs including liver, lung, bone, and brain. In such Musculoskeletal Kyphoscoliosis, short stature, pseudoarthrosis
cases, the assessment of the functions of these organs is import- (false joints), bone deformities
ant before choosing the anesthetic method. Excision of a skin Endocrine Delayed puberty, increase in number and
lesion can be performed safely using either general, regional, size of tumors during pregnancy
neuraxial, or local anesthesia. GI Chronic constipation, vomiting, diarrhea, pain

CNS ¼ central nervous system; GI ¼ gastrointestinal
Sneddon syndrome
This systemic disease is characterized by the association of livedo etiologies. In 1976, the diagnosis was postulated to be NF.
reticularis and cerebral ischemic arterial events (transient Merrick™s true condition, Proteus syndrome, a disorder of bone
ischemic attacks, strokes, or cerebral hemorrhages). It has a pre- and skin overgrowth rather than nervous tissue tumors, was only
identified in 1996.117 There are, as yet, no reports of pregnancy in
dilection for the female gender and pregnancies are possible,
although up to one-half of those with the disease become men- patients with Proteus syndrome.
tally impaired from strokes.113 Sneddon syndrome has been The manifestations of NF1, including those of the skin, are
linked to both the antiphospholipid syndrome (APS) and sys- listed in Table 19.8. For a comprehensive review of NF1 and
temic lupus erythematosus and is associated with a significant NF2 the reader is referred to Chapter 8.
rate of miscarriage and thrombosis. Livedo reticularis (LR) mani-
fests as a reticular pattern of fragile skin blood vessels. This skin
Lobular capillary hemangioma
vasculopathy has been described frequently in patients with APS
(pyogenic granuloma)
and its presence suggests valvular heart pathology and risk of
stroke. Livedo are classified according to the regularity and thick- These ˜˜pregnancy™™ tumors are found on the skin and the oral or
ness of the fishnet reticular pattern. The link between livedo nasal mucosa. Such growths occur in up to 5% of pregnant
woman.128 They are benign vascular pedunculated lesions that
reticularis and cardiac/central nervous system (CNS) thrombosis
supports more aggressive anticoagulation in patients with livedo present as friable red nodules that bleed easily with mild trauma.
than in patients who have APS without this manifestation.114,115 A coexisting gingivitis is often present, but no link with infection has
been established and thus the use of the term pyogenic is best
abandoned. Yuan and colleagues have suggested that elevated
Neurofibromatosis (von Recklinghausen
levels of estrogens and progesterones during pregnancy play an
disease)116,117,118,119,120,121,122,123,124,125,126,127
important role in the development of the granulomas. They found
Neurofibromatosis (NF) is an autosomal dominant genetic dis- that these hormones enhanced angiogenic factors in inflamed tis-
order that causes tumors of the nervous system. This progressive sue and inhibited apoptosis of the granuloma cells to extend the
angiogenic effect.129 Radical surgical treatment, often with pre-
disorder affects all races, all ethnic groups, and both sexes
equally. Neurofibromatosis has two genetically distinct forms: operative embolization, may be required in the extreme cases of
giant tumors.130 Otherwise, spontaneous involution occurs postpar-
NF1 and NF2. Neurofibromatosis type 1 is one of the most
common genetic disorders in the United States (one in every tum although recurrence during subsequent pregnancies is possible.
3 000 to 4 000 births). Neurofibromatosis was brought into public
Anesthetic considerations
view by the 1980 film, The Elephant Man, which detailed the life of
Joseph Merrick (1862“90). Physicians at the time Joseph Merrick The risk of nasal bleeding with minor trauma is increased in
lived and for nearly 100 years afterward believed he had elephan- pregnancy in general and particularly so in women with these
tiasis, a disorder of the lymphatic system having multiple hemangiomas. Uncontrollable gingival bleeding has reportedly



352
Chapter 19


led to induction of labor with the eventual need for emergency still lacking. Patients on biological therapy must always be treated
cesarean section for acute fetal distress.131 A complete airway with great care at the first clinical sign of sepsis. They are also to
evaluation is advised before induction of labor and nasal airways be monitored for the presence of granulomatous disease, espe-
and nasal tubes should be avoided. cially reactivated tuberculosis. As biologic agents are new, there
may be unforeseen consequences of their use.157 Various reports
illustrate this point.158,159,160 Three patients among 3000 partici-
Selected viral and bacterial diseases with
pating in clinical trials of natalizumab for treatment of multiple
dermatologic manifestations
sclerosis or Crohn disease developed progressive multifocal leu-
Currently available vaccines have altered significantly the inci- koencephalopathy, an opportunistic infection of the CNS caused
dence and management of a number of infectious diseases. These by reactivation of latent JC polyomavirus infection, and for which
vaccines include hepatitis A and B, diphtheria, tetanus, pertussis, there is no treatment. JC represents the initials of the first patient
haemophilus influenzae type b, poliovirus, measles, mumps, from which this species of human polyoma virus was isolated. It
rubella, and varicella. A recent report concluded that one-third has no relationship to Creutzfeldt-Jacob disease or ˜˜mad cow™™
of all children were under-vaccinated for more than six months disease, both of which are caused by prions (abnormal proteins)
during their first 24 months of life.143 This finding would infer that rather than viruses.
sporadic epidemics of these diseases will occur. The clinical diag-
nosis will often be difficult for the current generation of physi-
C1-esterase inhibitor deficiency (hereditary
cians who have often not seen clinical demonstrations of the
angioedema)
suspected viral exanthems. The clinical disease presentation
may further be altered by partial immunity from (inadequate) C1-esterase inhibitor (C1-INH) deficiency is a rare disorder of the
vaccinations. See Tables 19.9 and 19.10. complement system characterized by episodes of cutaneous or
mucosal edema of the skin, gastrointestinal tract, and upper air-
way.161 Airway instrumentation or minor trauma may cause life-
Autoimmune diseases with dermatologic
threatening airway edema. Gastrointestinal obstruction may
manifestations
occur. Griffiths and O™Sullivan162 concluded that regional
Autoimmune diseases with dermatologic manifestations are anesthesia is the safest anesthetic technique for a parturient
summarized in Table 19.11. Rheumatologists now primarily treat with C1-INH deficiency and that airway instrumentation should
these diseases. The more severe clinical manifestations require be avoided when possible. Elective C/S should be considered if
treatment regimens including systemic steroids, antimetabolites there are predicted difficulties with vaginal delivery. Prophylactic
(immunosuppressants), and biologicals. As these diseases are all fresh frozen plasma can be used before labor or obstetric surgery

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