|CASE BASED REVIEW
|Ahead of print publication
An unusual case of vomiting and arthritis: A diagnostic enigma
Shivraj Padiyar1, Daisy Doley1, Ramesh Babu2, John Mathew1
1 Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India
|Date of Submission||29-Dec-2020|
|Date of Acceptance||30-Mar-2021|
Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Sarcoidosis is a multisystem inflammatory disorder, which can have a myriad of presentations, with atypical presentation not being uncommon. Unless the clinician has a strong suspicion of sarcoidosis, it can be easily missed out. Here, we present an interesting case of a 44-year-old gentleman who had presented with inflammatory arthritis and vomiting. His serum cortisol levels were low. On further evaluation, he was found to have panhypopituitarism. Magnetic resonance imaging brain showed infiltrative disease involving the pituitary stalk. Imaging of the chest revealed mediastinal nodes which showed nonnecrotizing granulomatous inflammation on histopathology. After ruling out infectious causes a diagnosis of sarcoidosis was made, and the patient had a full recovery with steroids and methotrexate. Sarcoidosis can be a great mimicker presenting with a myriad of complications. Clinicians must be aware of the atypical presentations to diagnose the disease earlier.
Keywords: Arthritis, hypophysitis, panhypopituitarism, sarcoidosis, vomiting
| Introduction|| |
Sarcoidosis is a multisystem inflammatory disorder, which can have a myriad of presentations with atypical presentation not being uncommon. Unless the clinician has a strong suspicion of sarcoidosis, it can be easily missed. We describe here a case report of a patient with sarcoidosis who had presented with atypical initial presentation vomiting and arthritis.
| Case Report|| |
A 44-year-old man presented with a history of nondeforming inflammatory polyarthritis of small and large joints for 5 months. He also complained of persistent vomiting and significant weight loss over the past 5 months. There was no history of fever, skin rash, or any symptoms suggestive of a connective tissue disorder. He was treated with nonsteroidal anti-inflammatory drugs for his illness with no improvement. On examination, he was moderately nourished (Body mass index = 20.9 kg/m2) with a blood pressure of 100/70 mmHg. The skin was dry with scant body hair. Musculoskeletal examination revealed swelling and tenderness of bilateral small joints of hands (wrist, metacarpophalangeal joints, and proximal interphalangeal joints), elbows, and shoulders. The rest of the systemic examination was normal. At this point, the clinical differentials considered were connective tissue disorders such as Rheumatoid arthritis, Sjögren syndrome, or a paraneoplastic process. On laboratory evaluation, he was found to have normocytic normochromic anemia (Hb-11g/dl) and transaminitis. His serological markers (rheumatoid factor, anti-cyclic citrullinated peptide, and anti-nuclear antibodies were negative). The detailed investigations are shown in [Table 1]. Imaging of the hand [Figure 1]a revealed juxta-articular osteopenia. Considering weight loss and persistent vomiting not responding to anti-emetics, a gastroscopy was done to evaluate the upper gastrointestinal tract, which was normal. A possibility of Addison's disease was considered at this point. 8 AM serum cortisol level was found to be low: 2 mcg%, (10–20 mcg/dl). Since there was no history of exogenous steroid intake, iatrogenic (Hypothalamo-pituitary axis) suppression was considered unlikely. There was no history of headaches or any visual symptoms. A detailed workup for other hormones revealed normal adrenocorticotropic hormone (16 pg/ml) (0–46), low thyroid-stimulating hormone of 0.151 mIU/ml (0.3–4.5) along with T4 of 5.8 mcg/dL (5–12 mcg/dL). LH was <0.10 mIU/ml (0.8–7.6), follicle stimulating hormone <0.19 mIU/ml (0.7–11.1), testosterone <20 ng/dl (270–1030ng/dl) and prolactin 49.6 ng/ml (<20 ng/dl). Growth hormone deficiency was affirmed by a low baseline measurement of (Insulin-like growth factor 1). Blood sugars and electrolytes were normal and there was no evidence of diabetes insipidus. Given hypogonadotropic hypogonadism, adreno-cortical insufficiency, central hypothyroidism, and hyperprolactinemia, panhypopituitarism was considered. Magnetic resonance imaging (MRI) brain [Figure 1]b was done which showed thickening and enhancement of the pituitary stalk with a normal pituitary gland, suggestive of hypophysitis.
|Figure 1: Radiological images of the patient. (a) Plain radiographs of hands, AP view showing juxta-articular osteopenia. (b) Magnetic resonance imaging brain with gadolinium contrast showing thickening and enhancement of the pituitary stalk measuring around 4 mm × 3 mm (AP × TR) in T1W saggital section with normal pituitary gland. (c) Contrast-enhanced coronal sections of the thorax showing enlarged right lower paratracheal lymph node (Yellow circle)|
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Due to the presence of inflammatory polyarthritis, negative serologies, and hypophysitis, the differentials considered were infiltrative, infective, or inflammatory causes such as sarcoidosis, tuberculosis, lymphoma, or IgG4 disease. Chest X-ray did not reveal any abnormality. Mantoux test was negative. Serum angiotensin-converting enzyme (ACE) level was 25 U/L (Normal: 8–52 U/L) and ophthalmological evaluation was normal. A contrast cross-sectional imaging with high-resolution images of the chest [Figure 1]c revealed a few mediastinal nodes, maximum measuring up to 12 mm without any parenchymal infiltrates. Endobronchial ultrasound (EBUS)-guided fine needle aspiration cytology was performed from the right lower paratracheal lymph node which showed nonnecrotizing granulomatous inflammation [Figure 2]a and [Figure 2]b. Gene X pert and TB polymerase chain reaction on the biopsy was negative. A possibility of malignancy/lymphoma was considered less likely because of normal lactate dehydrogenase, uric acid, and peripheral blood picture. Hence, a diagnosis of sarcoidosis with arthritis, lymphadenopathy, and hypophysitis was considered. He was started on low-dose steroids, hydroxychloroquine, and Methotrexate at 15 mg/week after which there was a marked improvement in his symptoms of vomiting, arthritis, and mood within a week. Our patient was also started on replacement doses of oral thyroxine and monthly injectable testosterone and he is doing well after 9 months of diagnosis and follow-up.
|Figure 2: (a and b) (×40 and ×100): Fine needle aspiration smear from lymph node showing epitheloid granuloma containing cluster of loosely cohesive epithelioid histiocytes with pale, elongated sole-shaped nuclei, very few lymphocytes and no necrosis|
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| Discussion|| |
Sarcoidosis is a relatively common multisystem inflammatory condition characterized by noncaseating granulomas, which is a result of a complex interplay between the immune cells and their mediators. The etiology of sarcoidosis is unclear. It commonly occurs between the ages of 20 and 60 years of age.
Pulmonary involvement is seen in 90% of cases of sarcoidosis, predominantly in the form of upper lobar pathology, but it can involve any area of the lung. Central nervous system involvement is most often seen in association with systemic involvement. The prevalence of neurosarcoidosis (NS) is 5%–15% of which in 50% of cases, it is the initial manifestation of the disease. In our case too, neurological involvement was the presenting manifestation. One-third of patients with NS have or develop more than one neurologic manifestation of their disease. The cranial nerves, hypothalamus, and pituitary glands are most commonly involved in the nervous system. Being an infiltrative disease, it can involve the hypothalamohypophyseal region resulting in neuroendocrinological dysfunction whereas a primary pituitary defect and an empty sella occur rarely.,, Empty Sella usually is the result of infiltration into the stalk, intrasellar, or suprasellar mass lesion. The alternative school of thought is hypothalamic insufficiency could be the major cause of pituitary dysfunction. Hypothalamic-pituitary (HP) sarcoidosis occurs in <10% of patients with NS.
The infiltrative process is patchy, resulting in various combinations of anterior and posterior pituitary hormone dysfunction and sometimes isolated dysfunction. Diabetes insipidus and hyperprolactinemia are the main endocrine abnormalities in hypothalamic sarcoidosis. Hyperprolactinemia normalizes after the treatment of sarcoidosis and is reported to occur in 3%–32% of patients. Gonadotropin deficiency has been reported to be the most frequent manifestation of the disease in hypothalamic sarcoidosis. In our patient, there was no evidence of diabetes insipidus, hypernatremia, or hypovolemia. However, he had central hypothyroidism, growth hormone deficiency, hypogonadotrophic hypogonadism, adrenocortical insufficiency, and hyperprolactinemia, which favors hypothalamo-pituitary involvement of sarcoidosis. The cause of hyperprolactinemia may be explained by the loss of inhibition by dopamine on the posterior pituitary due to the involvement of the pituitary stalk.
The diagnosis of NS ideally requires systemic evidence of sarcoidosis on imaging and histopathology. In patients with NS, the chest X-ray is abnormal in only 30% of cases at presentation. Serum ACE lacks sensitivity and specificity. The ACE level is normal in almost two-thirds of the patients with HP sarcoidosis. Our patient reported a normal serum ACE level. One explanation for low ACE levels may be the low mass of sarcoid granuloma. Corticosteroids with other immunosuppressive agents remain the mainstay of treatment of NS. An alternative treatment with radiotherapy has been tried, with variable success. The prognosis of NS is poor with 10%–18% mortality.
Arthritis, which is present in 25% of cases of sarcoidosis, is of two types: the more common acute type and the less common chronic type. Acute arthritis is usually associated with Lofgren syndrome and is self-limiting. When a patient presents with chronic symmetrical inflammatory arthritis, co-existent rheumatoid arthritis needs to be ruled out. Our patient had a negative rheumatoid factor and anti-cyclic citrullinated peptide. Because of mediastinal nodes and hypophysitis, a diagnosis of tuberculosis was also considered. However, the possibility of Poncet's arthritis was ruled out, as arthritis completely resolved just with steroids which are a strong point against the diagnosis of Poncet's arthritis.
In our case, making a definitive diagnosis was challenging because of the atypical presentation of inflammatory arthritis with persistent vomiting as the first presentation of isolated NS without any characteristic neurological features, pulmonary involvement, or other systemic features like a fever. Hormonal assays and MRI imaging helped in making the diagnosis of hypopituitarism. The etiology of hypopituitarism was difficult to establish without a biopsy from the lesion. However, the EBUS guided FNA could be done from a paratracheal lymph node, showing a nonnecrotizing granulomatous inflammation which clinched the diagnosis. Our patient responded very well to steroids, methotrexate and hormonal replacement and he is doing well after 9 months of follow up.
| Conclusion|| |
NS must be kept in mind as one of the uncommon differentials in a patient presenting with hypopituitarism even in the absence of typical skin and lung involvement. Clinicians must be aware of presentations due to anterior pituitary hormonal deficiencies which could be the initial manifestation. Timely diagnosis and initiation of immunosuppression and hormone replacement lead to good prognosis in a patient with panhypopituitarism due to sarcoidosis.
Written consent of the patient was taken for publication.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
We thank the Department of Radiology and Endocrinology, CMC, Vellore for their contributions.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]