全身性疾病的風濕學表癥
賴振宏
學習目標：
了解一些全身性疾病如肝炎、糖尿病、內分泌疾病及癌症所可能出現的風濕表癥。
前言：
有相當多的疾病都或多或少的表現出一些風濕病的特徵,道理很簡單，我們雖然以疾病所主要影響的器官來命名，如肝炎、腎炎、淋巴癌，這些疾病的成因及其所影響的層面都是相當廣泛的，我們的免疫系統更是首當其衝，於是一些風濕的症狀於焉而生，這裡，我們很難將這些會表現風濕症狀的疾病一一提出討論，我們也不易依鑑別診斷的方法由風濕的表癥一一去判斷可能引起此風濕症狀的疾病，因此，我們將採取折衷的方法，先就一些常見的全身性疾病，去探討它們所可能伴隨的風濕症狀，也用一些針對風濕的表癥去研判所可能引發的相關的疾病。
Ｃ型肝炎：Ｃ型肝炎是一種小的RNA病毒，它與造成登革熱和黃熱病的病毒同屬於一個家族的病毒，Ｃ型肝炎和Ｂ型肝炎一樣，都會造成一些風濕的表徵，由於這些表癥有諸多雷同之處，我們將以Ｃ型肝炎為代表來討論。
慢性Ｃ型肝炎所表現出來的風濕症狀主要是由mixed
cryoglobulinemia syndrome (MCS)的方式來呈現，在MCS的病人中，其冷凝況澱物（cryoprecipitate）是一種單株的成分（如IgM類風濕因子）和多株的IgG（polyclonal
IgG），這類病人有80∼90%的機會可找到HCV的存在，且亦有證據顯示，HCV的感染直接與MCS的產生有關，這類的病人通常也會有補體下降的現象，這主要原因為冷凝蛋白和免疫複合體對補體產生的活化作用所造成，MCS的臨床表癥包括像多發性關節炎，腎絲球腎炎、血管炎、倦怠、神經炎、肺炎……等等。此外，也可查到冷凝蛋白的存在，但MCS的症狀不一定上述的種種情形都會表現，有時只表現其中的一種或兩種如血管炎、關節炎或腎炎（incomplete
MCS）。在一些HCV感染的病人中，儘管臨床的症狀並不明顯，約75%的病人類風濕因子呈陽性反應，1/3的病人血清中有冷凝蛋白，這種情形的產生可能與病毒直接侵害淋巴球和引起免疫複合物產生的機轉有關，但目前並不清楚，為何有些慢性Ｃ型肝炎的病人，不會表現風濕的症狀，也沒有可偵測得到的一些免疫異常，這顯示Ｃ型肝炎所引起的免疫問題及臨床症狀是由多種因素所共同調節產生的。
此外，15%
MCS症狀的病人會有sicca
syndrome的表現，這與早期有些報告顯示HCV的病人會合併sicca
syndrome的發生是吻合的。除sicca
syndrome及一些非特異的風濕症狀外，間斷有些報告，HCV感染的病人有polyarteritis
nodosa，SLE或Rheumatoid
Arthritis的表癥。
Ｃ型肝炎與風濕症狀的關係提醒我們兩點，一是在診治慢性發炎性關節炎的病人時，必須把HCV感染的可能列入。其二是，當我們使用一些具肝臟毒性的藥物如Methotrexate，NSAID治療病人而合併有肝功能異常發生時，我們必須考慮病人是否合併有HCV的感染。
為便於系統性的整理，以下就內分泌及腫瘤所可能合併的一些風濕性表癥以圖表方式表示出來。
治療：一般而言，如果風濕病的表癥是由於其他原因如癌症，或內分泌失調所引起，只要糾正原來的問題，風濕病症便可迎刃而解，不須特別的治療。
參考文獻：1.Wener MH et al. Hepatitis C Virus and Rheumatic Disease, J. Rheumatology 23:953-958, 1996.
2.Kelley et al. Textbook of Rheumatology 5th Edition, 1997.
3.Lawrence M. et al. Current Medical Diagnosis & Treatment 35th Edition, 1996.
Rheumatic Manifestations in Endocrine Disorders
|
|
Rheumatic Disorder |
Characters of Rheumatic Manifestations |
|
DIABETES MALLETUS |
Osteoarthritis Diabetic
hand syndrome Flexor
tenosynovitis Calcific
peritendinitis and bursitis Carpal
tunnel syndrome Neuropathy Charcot's
arthropathy Diabetic
osteopathy Diffuse
idiopathic skeletal hyperostosis (DISH) Miscellaneous manifestations |
In
diabetic animal model, DM enhances cartilage destruction, especially in
adult-onset DM. Less likely to have osteophyte formation. In
30-50% of type-I diabetes and-II diabetes. It correlates with the
appearance of renal or retinal microvascular disease. It results in
flexion contracture and limited joint mobility. It
happens in 1/3 diabetic patients and results in trigger finger or
Dupuytren's contracture of the palmar fascia. It
predominantly involves shoulder and causes severe adhesive capsulitis. It
can also appear as RSDS pictures. Nocturnal
parenthesis in first 4 finger or thenar muscles. Polyneuropathy
or mononeuritis. In
patients with DM and peripheral neuropathy. The involvement of tarsus and
ankle may cause painless deformity of the foot. It
causes osteolysis of the bones of the forefoot. It can rapidly expand from
patchy osteopenia to complete reabsorption in distal metatarsal joints and
proximal phalanges. It
rarely involves sacroiliac joints which is different from ankylosing
spondylitis. Septic arthritis, Gouty arthritis, CPPD deposition, Frozen shoulder, and Neuropathic joints. |
|
HYPERPARATHYROIDISM |
Osteoporosis Painless
proximal muscle weakness Arthritis Osteitis fibrosa cystica |
May
cause crush fracture. Normal
CPK and aldolase. EMG may show pattern of myopathy or neuropathy. Muscle
biopsy does not show evidence of inflammatory cell infiltration. Evidence
of erosion and chondrocalcinosis may be found. These patients are
relatively older and have high serum calcium level. Crystal deposition
such as calcium pyrophosphate, calcium apatite and calcium oxalate are
occasionally found. A form of renal osteodystrophy. Erosive lesions involves hands, clavicle and axial skeleton which may be similar to neuropathic arthropathy. |
|
· HYPOPTH |
Spondylitis Short
metacarpal joints Albright's
hereditary osteodystrophy |
Similar
to DISH. The
result of premature epiphyseal closure. Knuckle-Knuckle-dimple-Knuckle sign (short 4th metacarpal bone). Deformities involves hips, knees and pelvis. |
|
HYPERTHYROIDISM |
Thyroid
acropathy Painless
proximal muscle weakness Osteoporosis Autoantibodies |
Uncommon
manifestation of Grave's disease. It presents as distal soft tissue
swelling, clubbing, periostitis, especially the metacarpal bone. It
frequently associates with exophthalmos and pretibial myxedema. No
elevation of CPK. It happens in 70% of hyperthyroidism patients. Increased
bone resorption. Anti-DNA
antibody is present in 90% patients. SLE is only found in few cases with
hyperthyroidism.
|
|
HYPOTHYROIDISM |
Myxedematous
arthropathy Inflammatory
arthritis Myopathy Carpal
tunnel syndrome Osteonecrosis Miscellaneous |
It
usually involves large joints. It causes swelling and
stiffness. CPPD can be detected commonly with no inflammatory joint fluid.
The replacement of the thyroid hormone corrects the arthropathy. It
associates with Hashimoto's disease and resembles
rheumatoid arthritis. If RF is positive, the disease is more aggressive,
if it is negative, the disease is relatively moderate. The
picture may resemble polymyositis when CPK is elevated or resemble
polymyalgia rheumatica when stiffness, painful muscle is the chief
complaints. In 7%
patients. The disease may be due to the compression of median nerve by
mucinous material accumulation or due to intrinsic neuropathy. It
primarily involve hip joint. Unexplained
carpal tunnel syndrome, polymyalgia rheumatica with normal ESR, gout,
Raynaud's phenomenon, polymyositis with normal muscle biopsy. All these
manifestations can be reversed by thyroxin therapy.
|
Rheumatic
Manifestations of Paraneoplastic Syndromes
|
Manifestations |
Important pictures |
Associated cancers |
|
Hypertrophic Osteoarthropathy |
Clubbing finger, periostitis of long bones |
Bronchogenic carcinoma, carcinoma of esophagus, liver, colon. Lymphoma |
|
Amyloidosis |
Macroglossia, cardiomegaly, proteinuria, hepatomegaly, neuropathy |
Myeloma, Medullary carcinoma of the thyroid |
|
Secondary gout |
Pattern of gouty arthritis |
Myeloproliferative or Lymphoproliferative diseases, solid tumor malignancy |
|
Carcinoma Polyarthritis |
May simulate RA or involve in asymmetric joints. Predominantly over lower extremities with sparing of wrists and small joints of hands |
80% of women are due to breast cancer, otherwise no predominant malignancy reported |
|
Jaccoud's-type arthropathy |
Rapidly developing, nonerosive, deformity, yet painless arthropathy, predominantly over upper extremities and symmetrically involve small joints |
Carcinoma of lung |
|
Lupus-like syndrome |
Lupus-like |
Hodgkin's disease, myeloma, colon, breast and lung cancer, ovarian adenocarcinoma |
|
Necrotizing vasculitis |
Most likely cutaneous vasculitis picture, such as palpable purpura, maculopapular rashes |
Leukemia, lymphoma |
|
Cryoproteins |
Raynaud's phenomenon, purpura, circulatory impairment, gangrene |
Plasma cell myeloma, metastatic malignancies |
|
Immune complex diseases |
Nephrotic syndrome |
Hodgkin’s disease |
|
RSDS |
Palmar fascitis |
Ovarian carcinoma |
|
Scleroderma |
Picture of scleroderma or overlaps with dermatomyositis |
Adenocarcinoma and carcinoid tumor, metastatic melanoma |
|
Polyarteritis |
Picture of arteritis |
Hodgkin’s disease, hairy cell leukemia, solid tumor |
|
Polymyalgia rheumatica |
Polymyalgia, temporal arteritis, high ESR |
Solid tumor, hematologic malignancies and metastatic tumor |
|
Panniculitis |
Subcutaneous nodules and arteritis due to fat necrosis |
Pancreatic cancer |
|
Polychondritis |
Auricular polychondritis, nasal chondritis, polyarthritis |
Leukemia, lymphoma, myelodysplastic syndrome and solid tumor |
|
Pyogenic arthritis |
Culture of enteric bacteria such as clostridium septicum, Neisseria menigitidis |
Colon cancer, multiple myeloma |
|
Digital necrosis |
Severe Raynaud's phenomenon, high ANA titer |
Renal cell carcinoma and variety tumors |
|
Erythromelalgia |
Severe burning pain, erythema, warmth of extremities (feet >hands) |
Myeloproliferative disorders |
|
Antiphospholipid antibody (APA) syndrome |
Thromboembolic disorders and presence of APA. Disappearance of the symptoms and APA after removal of the tumors |
No predominant tumors |
考題：
1.糖尿病的病人比較不容易合併有下列那種疾病的發生﹖
(1)SLE (2)Septic arthritis (3)Gouty Arthritis
(4)pseudogout
2.糖尿病人合併有退化性關節炎時，下列何者並非其特徵
(1)易造成關節面狹窄 (2)易見到大量的骨刺增加
(3)多半在年紀較大的病人 (4)關節疼痛是其臨床表癥
3.副甲狀腺功能過高所造成的肌肉無力，下列何項敘述並非其特徵：
(1)肌肉無力以近側端肌肉無力較常見
(2)一般CPK可能正常
(3)EMG可能呈現肌肉或神經的病變
(4)肌肉切片檢查常可見到大量發炎細胞浸潤在肌肉。
4.一位60歲男性患者胃口不佳，體重減輕而住院，理學檢查發現有clubbing
finger（杵狀指），長骨Ｘ光檢查發現有periosteal
reaction，在考慮有惡性腫瘤存在的可能時，下列那一種器官的腫瘤可能性最高﹖
(1)肝 (2)腎 (3)肺 (4)胃
5.Ｃ型肝炎患者所引起的mixed
cryoglobulinemia syndrome的全身性症狀，最有可能與下列那一種致病機轉有密切的關係﹖
(1)巨大細胞的活化和分泌一些致病因子。
(2)Ｔ細胞的毒殺作用。
(3)抗體和抗原的免疫複合物沉積。
(4)Ｔ細胞活化後分泌細胞間素。