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Table of Contents
SPECIAL FEATURE: CLINICOPATHOLOGICAL CONFERENCE
Year : 2018  |  Volume : 7  |  Issue : 2  |  Page : 86-93

A 21-year-old man, with ichthyosis, parotid swelling acute kidney injury


1 Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 Department of Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
3 Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
4 Department of Nuclear Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Date of Web Publication26-Mar-2019

Correspondence Address:
R Ram
Professor and Head, Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCSR.JCSR_37_18

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How to cite this article:
Aruna M, Suguna E, Krishna Reddy M H, Anil Kumar C V, Lakshmi B S, Chandra V S, Praveen N, Ranadheer M, Kalawat T C, Ram R, Prayag A, Sadasivaiah S, Kumar V S. A 21-year-old man, with ichthyosis, parotid swelling acute kidney injury. J Clin Sci Res 2018;7:86-93

How to cite this URL:
Aruna M, Suguna E, Krishna Reddy M H, Anil Kumar C V, Lakshmi B S, Chandra V S, Praveen N, Ranadheer M, Kalawat T C, Ram R, Prayag A, Sadasivaiah S, Kumar V S. A 21-year-old man, with ichthyosis, parotid swelling acute kidney injury. J Clin Sci Res [serial online] 2018 [cited 2019 Sep 17];7:86-93. Available from: http://www.jcsr.co.in/text.asp?2018/7/2/86/254979



A 21-year-old man came to this hospital with persistent vomiting of about 20 days' duration. The vomiting was associated with nausea. The vomitus used to be small in quantity, nonbilious and contained particles of food that was previously ingested. There was no haematemesis or haematochezia. About 5 days before, the onset of the presenting complaint, he had low-grade fever that lasted for about 7 days. A local doctor had prescribed painkillers for the fever. The patient was referred to this hospital because his renal parameters were found to be elevated.

There was no history of cough, breathlessness, haemoptysis or swelling of the body. There was no history of oliguria, dysuria or graveluria. There was no history of epistaxis, joint pains, photosensitivity, hair loss or red eyes. He was not a diabetic or hypertensive. Neither was he an alcoholic or smoker. From his young age, skin is dry, rough, scaly and flaky. He has been using topical creams and emollients for this problem but never took any native medicine internally. One month before the present admission, he was treated by a physician for mumps. He had received antibiotics and painkillers then. From then, he also noticed hoarseness and breathy voice quality.

On examination, his skin all over the body was dry. There were scratch marks.

There was no facial puffiness or pedal oedema. There was no pallor, no jaundice, no cyanosis, no clubbing, no koilonychia or lymphadenopathy. His skin was dry, rough and scaly. The pulse was 90/min regular with no radiofemoral delay. BP was 150/90 mmHg in right upper limb with patient both in supine and erect postures. Respiratory rate was 28/min and temperature 98.6°F. There was no thyromegaly.

Gastrointestinal system examination

Oral cavity examination revealed red-violet submucosal nodules with superficial ulcers, nontender and circumscribed; pharynx: no abnormality and abdomen: All areas were moving equally with respiration, soft, no tenderness and no organomegaly.

Respiratory system examination

Trachea central, no flattening or bulges on the chest wall, both sides of chest moving equally with respiration, resonant note on percussion all over the chest, vocal resonance is normal and equal on both sides, normal vesicular breath sounds, no crackles/rhonchi and no pleural rub heard.

Cardiovascular system examination

Apex beat is in 5th left intercostal space, half-an-inch medial to mid-clavicular line, normal cardiac resonance, normal first and second heart sounds and no added sounds.

Nervous system

Conscious and coherent. All mental functions, (cranial nerves and vide infra), motor and sensory systems were normal. There were no cerebellar signs or signs of meningitis. Gait was normal. Skull and spine were normal.

A few days after hospitalisation, it was noticed that his voice had turned hoarse. The hoarseness of voice worsened over the subsequent days. There was no difficulty in swallowing or speech. There was no nasal regurgitation of food while swallowing, deafness or a liability emotion. An ENT examination by indirect laryngoscopy revealed the left vocal cord palsy. The rest of cranial nerve examination was normal.

In the meanwhile, as the patients renal status of the patient continued to deteriorate, he was taken up for haemodialysis. After he was adequately dialysed he was subjected to a diagnostic procedure. Some of his laboratory test reports are given in [Table 1].
Table 1: Investigations

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Differential diagnosis (discussion by Dr M. Aruna, Postgraduate Junior Resident, Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati).

The patient had the following clinical features and investigations results. From his young age, skin is dry, rough scaly and flaky, oral cavity examination revealed red-violet submucosal nodules with superficial ulcers, nontender and circumscribed, 1 month before the present admission, he was treated by a physician for 'mumps', from then he also noticed hoarseness and breathy voice quality, urine examination revealed pus cell cast, hypercalcaemia, hypercalciuria and raised serum creatinine and blood urea. The clinical condition which included all these features yields the diagnosis.

One of the most dangerous errors in medicine is to try and fit all the available information into a tentative diagnosis. This form of error derives from a particular style of clinical reasoning, namely pattern recognition.[1] The pattern-recognition style is commonly used by primary care physicians and in casualty, where instant recognition of a disease is paramount. In our patient, a particular pattern is absent. Other types of reasoning include algorithmic, exhaustive (gathering every possible piece of data) and hypothetico-deductive (generating and rejecting) hypotheses as more and more data are collected. The latter is widely held up as the ideal, while the exhaustive approach is often used for rare diseases or unusual presentations. We are perhaps constrained to utilise algorithmic, exhaustive gathering of data to accomplish the diagnosis.[2]

From his young age, this patient had the skin dry, rough scaly and flaky. This description fits the condition, ichthyosis. The aetiology of ichthyosis includes congenital and acquired causes. The congenital causes are associated with an onset from birth and with corneal opacities, hair abnormalities, congenital heart defects and limb defects. The acquired causes are HIV infection in intravenous drug users, leukaemia, myelodysplastic syndromes, bone marrow transplantation, hypothyroidism, sarcoidosis, systemic lupus erythematosus and systemic sclerosis.

The list of oral manifestations of systemic diseases cannot be exhaustive at any time. This list may have broad rubrics-gastrointestinal diseases, haematologic disorders, nutritional diseases, endocrine disorders, drugs, connective-tissue disorders and cutaneous diseases [Table 2].
Table 2: Systemic diseases with oral manifestations

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By all means, the list is likely to be incomplete; yet based on clinical manifestations and investigations, it is possible to exclude all categories except connective tissue disorders and cutaneous diseases.

Before the present admission, the patient was treated by a physician for 'mumps'. From then the patient also noticed hoarseness and breathy voice quality. The listed complications of mumps include meningoencephalitis, orchitis, oophoritis, pancreatitis, transverse myelitis, cerebellar ataxia, myocarditis, sensorineural hearing loss, arthritis, thrombocytopenic purpura, mastitis, thyroiditis and keratouveitis. The hoarseness and breathy voice is not a reported complication of mumps. A PubMed search with keywords, 'mumps' and 'vocal cord palsy' did not yield a result. This leads to a logical rational inference, 'was it 'mumps'?'. The differential diagnosis of parotitis[3] was listed in [Table 3].
Table 3: Differential diagnosis of parotitis

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The patient also had a set of renal manifestations-persistent vomiting of 20 days' duration, serum creatinine was 10.8 mg/dL, serum potassium was 5.1 mEq/L, haemoglobin was14.1 g/dL, with normal sized kidneys. It suggested the diagnosis of acute kidney injury (AKI). The presence of pus cell cast suggested the diagnosis of acute interstitial nephritis (AIN). The major syndromes of nephrology are given in [Table 4].
Table 4: Major syndromes of nephrology[4]

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Urine is often regarded as a mirror of the (glomerular) soul?[5] even though urine betrays the pathology in other parts of the kidney [Table 5].
Table 5: Types of casts

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The majority of causes in this list can easily be excluded. The aetiology of AIN is given in [Table 6]. The patient has no obvious infection at present to account for the AIN. He used antibiotics and painkillers. However, we understood that he lacks several features to support his diagnosis [Table 7]. We are now left with the list of immune and neoplastic disorders.
Table 6: Aetiology of acute interstitial nephritis

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Table 7: Clinical characteristics of non-steroidal anti-inflammatory drug-induced acute interstitial nephritis versus typical drug-induced acute interstitial nephritis[6]

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The reported serum calcium was 10.5 mg/dL. When corrected for serum albumin 3.2 g/dL using the formula corrected serum calcium= (0.8 × [normal albumin-patient's albumin]) + serum Ca level it was = 0.8 × 0.8 + 10.5 = 11.1 mg/dL. The normal range of serum calcium is 8.8–10.7 mg/dL. The causes of hypercalcaemia were listed in [Table 8].
Table 8: Causes of hypercalcaemia[7]

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Several of the causes of hypercalcaemia could be excluded. Parathormone is 14.4 pg/mL. Hence, parathyroid-related disorders are excluded. There is no evidence of malignancy. Thyroid stimulating hormone was normal. There was no immobilisation, no use of thiazides and vitamin A. We have decided this to be an AKI. Hence, it was not due to chronic renal failure. Vitamin D-related disorders could still be a cause of hypercalcaemia.

The normal range of urine calcium excretion is 100–250 mg/day. 24 h urine calcium in this patient was 585 mg. The causes of hypercalciuria were given in [Table 9].
Table 9: Causes of hypercalciuria

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The patient also had breathy voice quality. It suggested vocal cord palsy. The vocal cord palsy could be due to several causes such as congenital causes, infectious causes, traumatic causes, endocrinologic (thyroid) diseases, neurologic diseases and systemic rheumatological diseases. Sarcoidosis, rheumatoid arthritis and scleroderma are rheumatological diseases which could have breathy voice quality.

An overview of all the relevant causes of each of the attributes of the patient is presented in [Table 10].
Table 10: Overview

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'When you have eliminated the impossible, whatever remains, however improbable, must be the truth?' The Sign of the Four (1890) by Sir Arthur Conan Doyle. This axiom is true in our analysis. In [Table 10], the common disease that was expressed by all clinical features is sarcoidosis.

'Sarcoidosis is a multisystem disease with protean manifestations[8] and can be a great masquerader'.[9] The diagnosis of sarcoidosis is firm when chest radiographic evidence is accompanied by compatible clinical features and noncaseating granulomas on biopsy, with all other causes of granulomas ruled out.[10]

The most common diagnostic signs of sarcoidosis are bilateral intrathoracic hilar lymphadenopathy or diffuse micronodular pulmonary infiltration at chest radiograph, associated with a typical lymphatic distribution or a galaxy sign on computed tomography (CT).[11] However, the absence of mediastinal and hilar lymphadenopathy and normal lung parenchyma on CT scan intrigued me. Noncaseating granuloma, albeit the sine qua non of sarcoidosis, with tuberculosis being endemic, the latter should also be excluded with conviction.

The chest radiograph may be normal in 5%–10% of patients with sarcoidosis.[12] There were reports of sarcoidosis without pulmonary involvement at presentation [Table 11].[13],[14],[15] There were five patients in three reports. Only one of them had cranial nerve palsies as presenting feature. The raised serum creatinine was a feature in one patient. The diagnoses in these patients were based on biopsy of the tissue which showed non-caseating granuloma. All patients improved after steroid therapy.
Table 11: Published reports of sarcoidosis without pulmonary involvement at presentation

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Pathologist's diagnosis (Dr E. Suguna, Postgraduate Junior Resident, Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati)

A renal biopsy revealed fourteen glomeruli. Glomeruli were normocellular with patent loops. Glomerular basement membranes showed no spikes or double contours. Multiple non-necrotising granulomas composed of lymphocytes and histiocytes with an abundant cytoplasm, open chromatin and prominent nuclei were present [Figure 1] and [Figure 2]. Occasional giant cells were also present. Interstitium was oedematous and was infiltrated with dense lymphocytes and a few plasma cells and eosinophils. There was no interstitial fibrosis or tubular atrophy. The Ziehl–Neelsen staining of renal biopsy did not show any acid-fast bacilli. It was opined to be a granulomatous interstitial nephritis. The differential diagnosis was sarcoidosis, tuberculosis and drug-induced granulomatous interstitial nephritis.
Figure 1: Non-necrotising granuloma showing giant cells (Haemoloxylin and eosin, ×20)

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Figure 2: Non-necrotising granuloma (PAS, ×10)

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Nuclear Medicine Physician's diagnosis (Dr Ranadheer Manthri, Associate Professor, Nuclear Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati): An:

18F-labeled fluoro-2-deoxyglucose/positron emission tomography-computed tomography scan revealed, intense uptake in the salivary glands, lungs and enlarged kidneys [Figure 3]. The uptake in salivary glands was akin to panda sign on a gallium-67 citrate scan. Panda sign is due to bilateral involvement of parotid and lacrimal glands superimposed on the normal uptake in the nasopharyngeal mucosa.[16]
Figure 3: 18F-labelled fluoro-2-deoxyglucose/computed tomography scan: Intense uptake in salivary glands, lungs and intense uptake in enlarged kidneys

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Final diagnosis by the Nephrologist (Dr Hari Krishna Reddy, Postgraduate Senior Resident, Nephology, Sri Venkateswara Institute of Medical Sciences, Tirupati): Acquired ichthyosis, oral submucosal nodules, bilateral parotid swelling, left recurrent laryngeal nerve palsy, hypercalcaemia, hypercalciuria, presence of pus cast and AKI all pointed towards sarcoidosis. The serum angiotensin-converting enzyme was found to be 271 IU/L (reference range: 12–68 U/L).

After confirming the diagnosis of sarcoidosis, the patient was treated with injection methyl prednisolone (15 mg/kg/day) for 3 days followed by oral prednisolone (0.5 mg/kg/day). After 2 weeks, he became independent of dialysis, and after 6 weeks, the serum creatinine declined to 1.5 mg/dL.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]



 

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