63歳男性 「つまむと痛い」

皆様
先日より困っているが症例が有りまして、皆様のご意見をうかがえればと存じます。 長い記述のうえに英語ですみません。膠原病関連疾患なのかどうか見当がつきません。どうぞよろしくお願い申し上げます。

Case: CC: 63 y/o fisherman presented with pinching induced pain all over his body below the neck.
Pt was able to catch shrimp boarding on boat until October 2006, when he developed neck and shoulder stiffness and had to be off from work. The stiffness over upper trunk turned more like a pain when triceps and shoulder muscles got pinched. He felt residual pain for 1-2 min off the pressure. He also felt dullness over low back and blt lower extremities. The dull pain is constant, worse on lying in LEs. The stiffness of upper trunk and low back- pelvic area became unbearable in 30 min when he repeatedly loaded bucket of shrimp on to the boat. Pt experienced spontaneous lightening pain in arms and legs everyday. He has no abnormal sensation above his neck.
Pt sought medical attention in several specialties at different hospitals since October. His lumber MRI showed L5/S1 stenosis. The dullness on low back appeared slightly improved with the local injection for 'spinal stenosis' at orthopedics, but the pinch induced pain became worse over time and spread throughout upper and lower trunk. He experienced pain even with the pressure when he rolls over in the bed and his sleep got disturbed.
His past medical hx is significant for untreated hypertension, and COPD dxd a year ago when he had SOB on exertion last winter. He has no sputum or cough, and no sig changes of DOE since last year. His left visual acuity had been weak since he had contracted 'measles' as child and was completely lost since retinal detachment in his 30s.
He takes no medication, no OTC meds or herbal medicine. No known drug allergies, He used to smoke 60pack year and quit 2 years ago. Occasionally drinks beer and no illicit drug use. No recent travel, and no pets or exposure to animal before this presentation. No transfusion. He lives with his wife and 2 grown children. His family hx is noncontributory.
ROS is negative for weight loss, night sweats, skin rash, visual changes, GI or GU sx.
Pt was mildly hypertensive but otherwise showed normal vital signs, and afebrile. He appeared developed and well appearing. Lt eye showed fixed pupil with no reactive to light. Remainder of HEENT, lung heart, abdomen, extremity, and skin exams were unremarkable. Neuro exam: CN2-12 intact and reflex are all normal. Sensation: significant for pinch induced pain below neck. Vibratory, cold temperature, or proprioception intact. Light touch sensation was mildly diminished in both feet. Motor 5/5 throughout. Coordination, Romberg and gait were all intact.
Given the distribution of neck thru shoulder girdle and low back stiffness, we tried prednisone 15mg qd for 5 days, assuming he might have PMR. Steroid was ineffective and was discontinued.
Lab: WBC 10,000 (N 75%, L 10%, E 8 %) Hb14.5 Plt nl LFT nl LDH nl BUN/Cr 20/1.2 (baseline) ESR 28/hr CRP 1.8mg/dl U/A: protein 1+ no casts
CXR nl
He remained symptomatic and the trial of tricyclic antidepressant was not promising. Pt lives far at the sea shore and requests inpatient w/u.
Additional blood work: ANA neg, RF neg, SPEP neg, ANCA neg, VDRL less than 1, TPHA x 160 (<80), Imaging studies at outside hospitals was reportedly all negative: - MRI of head, chest, abdomen, lumbar spine, pelvis - Nerve conduction test. - cystoscopy # Disabling pinching sensation (myalgia, neuralgia??) #mild eosinophilia #Dyspnea of exertion (smoker) #+syphilis antigen #mild elevation of inflammatory markers #L4/5 spinal stenosis My DDx on admission were only tabes dorsalis and eosinophilic myalgia syndrome. Pt was admitted yesterday and LP revealed 5/3 cell and normal protein/glucose. CSF VDRL is pending. Muscle and neck MRI were normal. Could this still be Tabes dorsalis　(despite no cells in CSF, no deep sensory deficit)? What other differential dx would account for this presentation?
（K先生）

　外来・病棟と駆け廻った後に書類を書きながら拝読しましたので、とんでもない勘 違いをしている可能性がありますが、"Small-fiber neuropathy"として鑑別を考える のはいかがでしょうか？
http://www.thecni.org/reviews/13-2-p07-treihaft.htm
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12210380&dopt=Abstract
年齢・社会的にどうかとも思いますが、小生なら一応HIV statusは調べるかもしれ ません。 　また、リウマチ性疾患の範疇で"Small-fiver neuropathy"を来たす疾患として、 Sjogren症候群は考えるかもしれません。
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12210380&dopt=Abstract
　合致しない点として、発症がDistalからではなく、Neck and Shoulderと、PMRを思 わせるような比較的体幹部から起きていることが挙げられます。（神経内科の先生 方、Followよろしくお願いします ＾＾;） 　Mild eosinophiliaに着目すると、漁の時（に限らず）思わぬものを食べていない か（残念ながら知識不足で具体的な寄生虫の名前が浮かびません）が気になります。
　取り急ぎお返事差し上げました。書類に戻ります。
（Rheum-dora）

　こんばんは。
　K先生の症例呈示を拝見して、ある患者さんのことを思い出しました。
35歳の女性で、慢性に経過した背部痛と両上肢痛を主訴に受診されました。 CXRでのBHLが契機となり、サルコイドミオパチー（chronic type）と診断した症例です。
私の鑑別診断は、梅毒、サルコイドーシス、結核、真菌感染症、HIV感染症、血管炎症候群、 lymphomaそして甲状腺疾患です。 また、Rheum-dora先生がおっしゃるように好酸球増多に着目するのも重要だと思います。
血清Ca、ACE、針筋電図、筋造影MRIそして筋生検を計画したいです。
（Y先生）

Rheum-dora先生、Y先生ご意見ありがとうございました。お二人とも考え方がしっかりされていて、とても勉強になりました。
ケースの簡単なまとめですが、63才漁師さん男性、数ヶ月間のprogressive　disabling shoulder/trunk/low back stiffnessとepisodic ligntening pain、神経学的所見はgrasp and pressure induced hyperesthesia of affected area以外所見なく、検査値では軽度の炎症と軽度好酸球増多、TPHA 陽性、CSF 大きな異常なしでした。前回きちんと述べていませんで したが、LDH nl, CPK nl, TSH nl, Calcium nl, 他院でのEGD, Colonogscopy negative, CT of chest and abdomen negativeでした。
追加検査結果では、HIV negative, CSF-VDRL negative, Nerve conduction test negative, MRI of quadriceps and cervical spine unremarkableでした。患者さんはtricyclic からcarbamazepineに変更されて2泊3日の検査入院後一度帰宅となりまし た。
神経内科の先生方もとても診断に苦慮されておられました。Current Dianosisという内科教科書の筆頭著者でもありNEJMのCPSでもおなじみのUCSFのティアニー先生にご意見を伺うことができたので、皆様にお伝えし­たいと存じます。長いのでお時間をとりますこと、お詫びいたします。

A very rare condition I thought of immediately was Stiff-man Syndrome (some call it Stiff-person Syndrome for　political correctness). This is thought to be an auto-immune syndrome, related possibly to type I　diabetes and other immune conditions. The early　symptoms are just like your patient's; I think you can find details on the internet. The EMG shows characteristic findings which Valium abolishes, unlike any other disease. Antibodies to glutamic-acid decarboxylase are found in most cases; sensory and　motor neurological examinations are normal however. It would be an early case, and the disease is slowly progressive; you might be able to help the patient with high-dose benzodiazepines or baclofen. This is so rare, however.
One always thinks of Ciguatera toxin poisining in a fisherman with neurological symptoms, but they are mostly sensory. The idea of eosinophilic fasciitis came to my mine. It usually causes more obvious non-pitting edema in the affected areas; a deep fascial biopsy is necessary for diagnosis. I don't think it is eosinophilia-myalgia syndrome. If I am not mistaken, this is caused by tryptophan in a food supplement, and has not been reported for a number of years.
Sometimes people keep supplements for long times in their homes, so you might ask him about that. Trichinosis causes severe myalgias with eosinophilia, but I don't think you have it in Japan; an antibody test confirms. One of my patients had it: he was a hunter, and ate undercooked meat of a bear. You could see if your patient has this hobby, and you would know better than I if it is found in Japan.
Some small-fiber neuropathies may cause similar symptoms to your patient's with a normal nerve-conduction test. In such individuals, repeated and careful neurological examinations, especially of sensation and strength, are useful. The lightning nature of the pains make me wonder about that.
It is interesting that he had a peripheral treponemal test positive, but maybe it is falsely so (compatible with autoimmune disease, as Mitsuyo knows well). However, a negative CSF VDRL rules out tabes; you are so smart to think of it! I once had a patient with these lightning pains and tabes: very dramatic. A small-fiber neuropathy can be paraneoplastic, and indeed, the entire picture concerns me for this.
I learned from the great Dr. Robert Fishman at UCSF years ago that unexplained neuromuscular syndromes should raise the question of a hidden malignancy. Your patient is in the correct age range for that, and you might seek it with endoscopy and abdominal-pelvic CT scans.
I agree that PMR is excluded by failure to respond to steroids. Most true myopathies, such as polymyositis, have easily demonstrated weakness, but your Hokkaido fisherman may be a strong man in whom loss of strength could be difficult to detect. Endocrine myopathies are painless; inflammatory myopathies have pain much of the time. The CK is not always elevated. Sarcoidosis is an often overlooked disorder capable of causing myopathy, and is common in Japan as I need not tell you.What does one do?
I would proceed as follows: 1. a deep muscle biopsy to include fascia, in an affected area 2. repeat of the muscle enzymes 3. an EMG, positive in 85% of myopathic processes 4. a CT of the type I mentioned 5. the antibodies mentioned for Stiff-man (person) Syndrome 6. a panel of autoantibodies, to include anti-parietal cell, anti-thyroglobulin, anti-microsomal; obvously SLE is in the mix, so ANA is necessary, but I think you have already performed that 7. consider a therapeutic trial of baclofen while awaiting the results 8. hold off on steroids unless everything is negative, and then consider a higher dose, say 40 mg. of prednisone daily 9. trichinella antibodies 10. and as always in the end, revisit the history 11. serum LDH, as lymphoma can do strange things clinically.

　また神経内科の先生方と相談しながら検査と経過を見ることにいたします。その後新たな展開がありましたらご報告申し上げます。
（K先生）

　Dr. Tierneyの鑑別診断としては、
１：Stiff-person syndrome ２：シガテラ中毒 ３：好酸球性筋膜炎 ４：Eosinophilia-myalgia syndrome ５：Trichinosis（旋毛虫症） ６：Small-fiber neuropathies ６-１：Paraneoplastic syndrome ７：Tabes dorsalis ８：Myopathies ９：サルコイドーシス
が挙げられているようです。やっぱりVascular, Infection...と順に考えていかれ たのでしょうか？

　今更のような質問で恐縮ですが、「つまむと痛い」というのは皮下をすこしつまん だだけでも痛いのでしょうか？それとも筋肉を大きくつかむようなGraspで痛みが誘 発されるのでしょうか？ 　最初、「筋肉ではなく神経のイベントかな?」と思った理由は、「つまむ」という 表現でなにか浅層のイベント、つまり皮膚やその部分の支配神経の問題をイメージし たからです。すこし早とちりだったかもしれません。また、「首から下すべて」との ことですが、Segmentalな要素はありませんでしたでしょうか？（Dorsal-root ganglionopathyを念頭に置いています）それとも神経学的なSegmentの要素はなく、 「体全体が痛い」としか表現できない局在(?)だったのでしょうか。
　Dr. Tierneyが「MyopathyでもCK上がらないことあるよ」とこっそり書いているの が興味深いです。
（Rheum-dora）

早速のご意見を頂きありがとうございます。病歴の記載がわかりにくくて申し訳ありませんでした。 患者さんは「つまむと痛い」「肩がこったような重だるい感じ」という表現をされます。「つまんで痛い」ですが、基本的には腹部の筋層よりも浅いレベルで皮膚や皮­下脂肪をつまんでも痛みが出ますし、ＴｒｉｃｅｐｓやDeotoidの筋肉をつかんでも痛みが出ます。筋肉痛なのかneuropathyなのかよくわからないの­ですが、分布はproximal優位です。皮下組織や筋肉をつまんで圧を加えたと同時に痛みが出るのはupper chest and shoulder areaですが、それより下は「つまんだ時の痛みよりもその後離してから1.2分痛みがジーンと残る」といいます。「腰から大腿にかけて重だるい痛み」が、漁業­の仕事をしていても出てきて辛くて仕事ができないし、横になって寝ていると下になった側に痛みと重だるい凝った違和感が出てきて眠れない、そうです。その他、体­のあちこち(体幹、両下肢）にびりっとした電撃痛が瞬間的にはしる、といいます。
膠原病リウマチ内科にご紹介いただくケースは難しいですね。またご意見をいただけますと幸いです。よろしくお願い申し上げます。
（K先生）