CHAPTER 8: CONNECTIVE TISSUE DISEASES Flashcards
Young adults
Dull red macules/indurated plaques with adherent scale—evolve with atrophy, scarring, pigment changes
Usually above the neck (scalp, nose, malar, lower lip ears)
Generalized- thorax, upper extremities, head and neck, may have alopecia
95% will remain confined to skin
Discoid LE
[Chronic cutaneous LE]
Large lesions, atrophic, hypopigmented, red or pink patches and plaques
Fine telangiectasia and scaling
Extensor/midline back usually affected
Prominent palmoplantar involvement
Lupus erythematosus-lichen planus overlap
Evolve as polycyclic annular lesions or psoriasiform plaques
Scale is thin and easily detached
Follicles not involved
Transient/migratory; no scarring
Tend to occur in sun exposed areas-face and neck, chest and back
3/4 have arthritis (+) anti Ro/SSA
Subacute cutaneous LE (SCLE)
Drug induced Subacute cutaneous LE (SCLE) is most often related to what drug
Hydrochlorothiazide
Also: ACE inhibitors, CCB, interferon, anticonvulsant
SLE must have how many of the criteria to diagnose
4/11
At least 1 clinical and 1 immunologic
or must have biopsy proven lupus nephritis in the presence of ANA or anti-dsDNA antibodies
SLE criteria
SOAP BRAIN MD
Serositis (pleuritis/pericarditis)
Oral ulcers
Arthritis
Photosensitivity
Blood low (leuko, thrombo, anemia)
Renal (protein >0.5g/day or casts)
ANA positive
Immunologic- dsDNA, anti-Sm
Neurologic- seizures, psychosis
Malar rash
Discoid rash
Difference between bullous lesions of lupus erythematosus (BLE) and epidermolysis bullosa acquisita
Dapsone effective in BLE and not in EBA
Earliest changes that may be noted in SLE
May remain the sole symptom for some time
Transitory or migratory arthralgia
Most common cause of death in SLE DURING the first 5 years
Inflammatory lesions and infections
Most common cause of death in SLE AFTER the first 5 years
Thromboses
Most frequent cardiac manifestation in SLE
Pericarditis
This sign is a marker for SLE patients at risk for CNS lesions (Sneddon Syndrome)
Livedo reticularis
Implicated causes of drug induced LE
HIP SPAM
Hydralazine
Isoniazid
Procainamide
Sulfonamides
Penicillin
Anticonvulsants
Minocycline
This test is positive in 95% of cases of SLE
ANA
This is specific but not sensitive to SLE
Indicates high risk of renal disease
Anti-dsDNA
Immunologic test for SLE that has 10% sensitivity but specificity is very high
Anti-Sm
Immunologic test that is common in Subacute cutaneous LE (SCLE) and Sjögren
Anti-La
(Immunologic test)
More commonly positive in SCLE, neonatal LE, late onset and Asian LE
Anti-Ro
Single most effective local treatment in SLE
Triamcinolone acetonide 2.5-10mg/mL at 4-6 weeks interval
Safest class of systemic agent for SLE
Antimalarials
Drug of choice for bullous systemic LE
Dapsone
First line systemic therapy in most forms of cutaneous LE
Hydroxychloroquine 6.5mg/kg/day
WOF this side effect of hydroxychloroquine
Ocular toxicity
When should Ophthalmology consult be done when administering hydroxychloroquine?
Ophthalmologic consultation should be obtained before, and at 4-month to 6-month intervals during, treatment.
Constriction of visual fields to a red object and paracentral scotomas are rare at the recommended dose, but even a small risk of loss of vision must be taken seriously. The finding of any visual field defect or pigmentary abnormal- ity is an indication to stop antimalarial therapy.
Side effect of Quinacrine in SLE tx
1.yellow discolor- ation of the skin and conjunctivae. 2. blue-black pigmentation of the hard palate, nail beds, cartilage of the ears, alae nasi, and sclerae.
3. Bullous EM, lichenoid drug eruption, nausea, vomiting, anorexia, and diarrhea may develop.
4. Aplastic anemia has rarely been noted in long-term therapy.
5.A patient’s brown or red hair may turn light blond.
Second line and third line agents for SLE
Retinoids are second-line agents and are particularly helpful in treating hypertrophic LE.
these are third-line systemic agents for cutane- ous LE.
systemic immunosuppressive agents are often required to manage the systemic manifesta- tions of LE, and these are third-line systemic agents for cutane- ous LE.
Inflammatory myositis and skin disease
Erythema and edema of face and eyelids, upper face—evolve to reticulated white scarring
Extensor surfaces may be similar to psoriasis
Photosensitivity
Dermatomyositis (DM)
Muscle group involved in dermatomyositis
called polymyositis (PM).
With or without skin lesions, weakness of PROXIMAL muscle groups is characteristic.
Erythema and scale over shoulder area in dermatomyositis is called
“shawl sign.”
Erythema and scale over hip area in dermatomyositis is called
“holster sign.”
Less common lesions but highly characteristic of dermatomyositis
Flat-topped, polygonal, violaceous papules over the knuckles (Gottron’s papules) are less common but highly characteristic of DM (Fig. 8-18).
In dermatomyositis, there is symmetrical muscle weakness, most commonly seen in
severe DM( dermatomyositosis)
Antibody positive in dermatomyositis
Positive anti-Jo-1 (histadyl tRNA synthetase) antibody
Diagnostic criteria for dermatomyositis must include:
How many
The following criteria are used to define DM/PM: (11)
- Skin lesions
- Heliotrope rash (red-purple edematous erythema on
upper palpebra) - Gottron’s papules or sign (red-purple flat-topped
papules, atrophy, or erythema on extensor surfaces and
finger joints) - Proximal muscle weakness (upper or lower extremity
and trunk) - Elevated serum CK or aldolase level
- Muscle pain on grasping or spontaneous pain
- Myogenic changes on EMG (short-duration, polyphasic
motor unit potentials with spontaneous fibrillation
potentials) - Positive anti-Jo-1 (histadyl tRNA synthetase) antibody
- Nondestructive arthritis or arthralgias
- Systemic inflammatory signs (fever >37°C at axilla,
elevated serum CRP level or accelerated ESR of >20 mm/h by Westergren method) - Pathologic findings compatible with inflammatory myositis
Criteria for diagnosis of dermatomyositis
Patients with the first criterion, skin lesions, and four of the remaining criteria have DM.
- Skin lesions
- Heliotrope rash (red-purple edematous erythema on
upper palpebra) - Gottron’s papules or sign (red-purple flat-topped
papules, atrophy, or erythema on extensor surfaces and
finger joints)
other: 4/8
* Proximal muscle weakness
* Elevated serum CK or aldolase level
* Muscle pain on grasping or spontaneous pain
* Myogenic changes on EMG
* Positive anti-Jo-1 (histadyl tRNA synthetase) antibody
* Nondestructive arthritis or arthralgias
* Systemic inflammatory signs (fever ,
elevated serum CRP level/ESR
* Pathologic findings of myositis
Patients lacking the first criterion but with at least four of the remaining criteria have PM.
Some patients with DM have little evidence of myopathy, and drug eruptions may mimic the characteristic rash.
Mainstay of acute treatment for dermatomyositis
PREDNISONE is the mainstay of acute treatment for DM patients, at doses beginning with 1 mg/kg/day, until severity decreases and muscle enzymes are almost normal.
Circumscribed or diffuse, hard, smooth, ivory colored areas that are immobile and give appearance of hidebound skin
Face expressionless, mouth constricted, claw like hands
Scleroderma
This form of scleroderma is more common in women
Macules or plaques, bands or guttate lesions
Rosy or violaceous — yellowish white
More common on trunk, margins surrounded by lilac border or telangiectases- skin elasticity lost
morphea form of scleroderma
Linear lesions that extend the length of the arm or leg and may follow lines of Blaschko
Begins during 1st decade of life
Linear scleroderma
Lesion in scleroderma that occur on the frontal scalp and extend partly down the forehead
en coup de sabre
Variant of scleroderma that has the most favorable prognosis
CREST syndrome
CREST syndrome acronym meaning
Calcinosis cutis
Raynaud phenomenon
Esophageal dysmotility,
Sclerodactyly,
Telangiectasia
First manifestation of progressive systemic sclerosis
Raynaud phenomenon is the first mani- festation of
progressive systemic sclerosis
Generalized disorder of connective tissue- thickening of dermal collagen bundles, fibrosis and vascular abnormalities in internal organs
“Woody edema” of the hands
3rd-5th decade
Progressive systemic sclerosis (PSS)
Criteria for progressive systemic sclerosis
Classic criteria include either proximal sclerosis or two or all of the following:
- Sclerodactyly (Fig. 8-25)
- Digital pitting scars of the fingertips or loss of substance
of the distal finger pad - Bilateral basilar pulmonary fibrosis
Localized forms of scleroderma must be excluded.
These criteria have been shown to be 97% sensitive and 98% specific for the diagnosis. The ACR has proposed an expanded list of criteria for PSS, as follows:
- Skin changes: tightness, thickening, and nonpitting induration, sclerodactyly, proximal scleroderma; changes proximal to the metacarpophalangeal or metatarsophalangeal joints and affecting other parts of the extremities, face, neck, or trunk (thorax or abdomen), digital pitting, loss of substance from the finger pad, bilateral firm but pitting finger or hand edema, abnormal skin pigmentation (often “pepper and salt”). The changes are usually bilateral and symmetric and almost always include sclerodactyly.
- Raynaud phenomenon: at least two-phase color change in fingers and often toes consisting of pallor, cyanosis, and reactive hyperemia
- Visceral manifestations: bibasilar pulmonary fibrosis not attributable to primary lung disease, lower (distal) esophageal dysphagia, lower (distal) esophageal dysmotility, colonic sacculations
90% of PSS patients have this symptom
The “neck sign” is described as a ridging and tightening of the neck on extension, occurring in 90% of patients with scleroderma.
Mainstay of medical treatment for Raynaud phenomenon
Vasodilating drugs—CCBs, angiotensin II receptor antago- nists, topical nitrates, and prostanoids—remain the mainstay of medical therapy for Raynaud phenomenon.
First line therapy for Raynaud phenomenon
CCBs such as nifedipine (Procardia XL), 30–60 mg/day, are often used as first-line therapy.
Defined by presence of:
Raynaud phenomenon
Arthralgia
Swollen joints
Esophageal dysfunction
Muscle weakness
Sausage like fingers
together with the presence of high titer anti-RNP antibodies in the absence of anti-Sm antibodies.
Mixed connective tissue disease (MCTD)
Antibodies present in Mixed connective tissue disease (MCTD)
high titer anti-RNP antibodies in the absence of anti-Sm antibodies.
Acute treatment for MCTD
For acute treatment, corticosteroids such as PREDNISONE (1 mg/kg/day) are effective for inflammatory features such as arthritis and myositis.
Chronic autoimmune disorder characterized by lymphocytic infiltration of exocrine glands (salivary and lacrimal)
Sjögren syndrome ( Sicca Syndrome)
Most definitive test for Sjögren syndrome
Labial salivary gland biopsy from inside the lower lip is usually regarded as the most definitive test for Sjögren syn- drome.
Typically, there is a dense lymphocytic infiltrate with many plasma cells and fewer histiocytes in aggregates within minor salivary glands.
Classic criteria for Sjögren syndrome
Classically, the diagnosis is made when there is objective evidence for two of three major criteria:
(1) xerophthalmia
(2) xerostomia, and
(3) an associated autoimmune, rheumatic, or lymphoproliferative disorder.
Antibodies present in Sjögren syndrome
Antibodies to fodrin, a major component of the mem- brane cytoskeleton of most eukaryotic cells, are present in some populations with primary and secondary Sjögren syn- drome.
IgA and IgG antibodies against α-fodrin are detected in 88% and 64%, respectively, in some studies. In other popula- tions, fodrin antibodies are less helpful.
About 80% of patients have anti-Ro/SSA antibodies; half as many have anti-La/SSB antibodies.
The rheumatoid factor is usually positive, and elevated ESR, serum globulin, and CRP and high titers of IgG, IgA, and IgM are common. Cryoglobulins may be demon- strated. Dendritic cells are increased in tissue during the early phases of the disease.
Patients with Sjögren syndrome are predisposed to the development of this malignancy
Patients with Sjögren syndrome are predisposed to the development of lymphoreticular malignancies, especially non- Hodgkin B-cell lymphoma.
